80009790 true Optimising community C(E)TRs through understanding the experience of people with learning disability and autistic people and investigating their impact on care OptiCaT 1. Do C(E)TRs reduce hospital admissions (primary outcome) and duration of hospital stay in people with learning disability and/or autistic people who are at risk of psychiatric hospital admission? 2. Do C(E)TRs improve other clinical, health and social outcomes? 3. Are C(E)TRs cost-effective? Background and study aims Care (Education) and Treatment Reviews, or C(E)TRs, were introduced in England in 2015 to help people with a learning disability and autistic people get the right support in the community and avoid unnecessary admission to a mental health hospital. However, there is limited evidence about how well C(E)TRs work. This study aims to find out whether community C(E)TRs reduce hospital admissions and improve people’s health, wellbeing and care. Who can participate? The study is for people aged 14 years or older who have a learning disability and/or are autistic, are receiving support from an NHS community mental health services, and are considered at increased risk of admission to a mental health hospital. Family members and paid carers of participants can also take part. What does the study involve? People with a learning disability and autistic people from different parts of England will be recruited to the study and followed-up over time. Researchers will collect information about hospital admissions, mental health, behaviour, quality of life, medication, use of health and social care services, and the care and support people receive. The information will be collected at the point of recruitment, at 6 months, and at 9 months. The information will be collected by questionnaires that a researcher will go through with the participant. The data that are collected will allow researchers to compare people who have a C(E)TR with people who do not. What are the possible benefits and risks of participating? People taking part may not receive a direct personal benefit. However, the information they provide may help improve C(E)TRs and the support provided to people with a learning disability and autistic people in the future. The study is considered to be low risk. Completing questionnaires and assessments will take some time and may be tiring. Interviews may involve discussing difficult experiences, including times when community care has broken down or when hospital admission has been needed, and this could be upsetting. Participants can take a break or stop an interview if they wish, and the research team will help them access appropriate support if needed. Where is the study run from? The study is led by King’s College London (UK), in partnership with Queen Mary University of London and other universities and NHS organisations. Participants are being recruited through NHS services in different parts of England so that the study includes people from a range of geographical areas and communities. When is the study starting and how long is it expected to run for? August 2025 to February 2028 Who is funding the study? The study is funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research Programme (reference NIHR158490) Who is the main contact? Dr Rory Sheehan, opticatstudy@kcl.ac.uk Admission to psychiatric hospital the modified version of the Adult Service Use Schedule (AD-SUS) and also provided by the clinician baseline, 6 months, and 9 months 1. Psychiatric symptoms measured using the Moss Psychiatric Assessment Schedule - Check (Moss-PAS (Check)) at baseline, 6 months, and 9 months 2. Behaviour that challenges measured using the Behaviour Problems Inventory - Short Form (BPI-S) at baseline, 6 months, and 9 months 3. Unmet care needs measured using the Camberwell Assessment of Needs for Adults with Developmental and Intellectual Disabilities - Research version (CANDID-R) at baseline, 6 months, and 9 months 4. Quality of Life measured using the 13-item WHOQOL Disabilities module (WHOQOL-DIS) at baseline, 6 months, and 9 months 5. Health-related quality of life measured using the EuroQoL Five Dimensions - Three Levels questionnaire (EQ-5D-3L) at baseline, 6 months, and 9 months 6. Service use (health and social care contacts) measured using a modified version of the Adult Service Use Schedule (AD-SUS) at baseline, 6 months, and 9 months 7. Family carer distress measured using the Kessler Psychological Distress Scale (K6) at baseline, 6 months, and 9 months 8. Family carer health-related quality of life measured using the EuroQol 5-Dimension 5-Level questionnaire at baseline, 6 months, and 9 months 9. Clinician-rated participant symptom severity measured using the Clinical Global Impression-Severity (CGI-S) Scale at baseline, 6 months, and 9 months 10. Clinician-rated participant health and social functioning measured using the Health of the Nation Outcome Scales (HoNOS) at baseline, 6 months, and 9 months 11. Clinician-rated participant exposure to restrictive practices (physical, mechanical, or chemical restraint) measured using a questionnaire created by the research team at baseline, 6 months, and 9 months 12. Psychotropic medication prescribing measured using a questionnaire created by the research team at baseline, 6 months, and 9 months Ethics approval required Leeds West Research Ethics Committee

NHSBT Newcastle Blood Donor Centre Holland Drive

Newcastle upon Tyne United Kingdom NE2 4NQ 25/YH/0119  10.1186/ISRCTN80009790 335048 NIHR: 158490 335048 158490 Observational Longitudinal study 2028-02-29T00:00:00.000Z United Kingdom England Oxleas NHS Foundation Trust

Pinewood House Pinewood PLACE

Dartford England DA2 7WG RPG@2.16.840.1.113883.2.1.3.2.4.18.48 South London and Maudsley NHS Foundation Trust

Bethlem Royal Hospital Monks Orchard Road

Beckenham England BR3 3BX RV5@2.16.840.1.113883.2.1.3.2.4.18.48 North London NHS Foundation Trust

4th Floor, East Wing St. Pancras Hospital 4 St. Pancras Way

London England NW1 0PE G6V2S@2.16.840.1.113883.2.1.3.2.4.18.48 East London NHS Foundation Trust

Robert Dolan House 9 Alie Street

London England E1 8DE RWK@2.16.840.1.113883.2.1.3.2.4.18.48 Central and North West London NHS Foundation Trust

Trust Headquarters 350 Euston Road Regents PLACE

London England NW1 3AX RV3@2.16.840.1.113883.2.1.3.2.4.18.48 Lincolnshire Partnership NHS Foundation Trust Hq

NHS Foundation Trust Carholme Court Long Leys Road

Lincoln England LN1 1FS RP7SG@2.16.840.1.113883.2.1.3.2.4.18.48 Sussex Partnership NHS Foundation Trust

Trust Hq Swandean Arundel Road

Worthing England BN13 3EP RX2@2.16.840.1.113883.2.1.3.2.4.18.48 Cornwall Partnership NHS Foundation Trust

Carew House Beacon Technology Park Dunmere Road

Bodmin England PL31 2QN RJ8@2.16.840.1.113883.2.1.3.2.4.18.48 Cheshire and Wirral Partnership NHS Foundation Trust

Trust Headquarters Redesmere The Countess of Chester Health Park Liverpool Road

Chester England CH2 1BQ RXA@2.16.840.1.113883.2.1.3.2.4.18.48 Tees, Esk and Wear Valleys NHS Foundation Trust

Trust Headquarters West Park Hospital Edward Pease Way

Darlington England DL2 2TS RX3@2.16.840.1.113883.2.1.3.2.4.18.48 Hertfordshire Partnership N H S

Harper Lane Shenley

Radlett England WD7 9HQ V09887@2.16.840.1.113883.2.1.3.2.4.18.48 North East London NHS Foundation Trust

Goodmayes Hospital 157 Barley Lane

Ilford England IG3 8XJ RAT@2.16.840.1.113883.2.1.3.2.4.18.48 Surrey and Borders Partnership NHS Trust Hq

18 Mole Business Park Randalls Road

Leatherhead England KT22 7AD RXXHQ@2.16.840.1.113883.2.1.3.2.4.18.48 South West London and St George's Mental Health NHS Trust

Springfield Hospital 61 Glenburnie Road

London England SW17 7DJ RQY@2.16.840.1.113883.2.1.3.2.4.18.48 false 1. Children/adolescents (aged between 14 and 17 years, inclusive) or adults (≥18 years) with a clinical diagnosis of learning disability (of any degree) or autism (diagnosis based on service records, expected to conform to ICD-10 chapter F7- criteria for learning disability or ICD-10 F84 criteria for autism) 2. Under the care of a community mental health service (e.g., Child and Adolescent Mental Health Services [CAMHS], Community Learning Disability Team [CLDT], Community Mental Health Team [CMHT]) in a participating Trust 3. Rated as red or amber on the Dynamic Support Register (DSR) 4. Provide informed consent to taking part or, where an adult lacks capacity to consent to participate, a personal or nominated consultee has signed a declaration form or, in the case of children/adolescents (<18 years), a parent/guardian has signed a consent form Mixed 14 Years 99 Years All 300 0 1. No clinically-confirmed diagnosis of learning disability or autism 2. Not on the Dynamic Support Register 3. Currently admitted to a psychiatric hospital 4. Does not provide informed consent or, where an adult lacks capacity, there is no consultee declaration or, in the case of children/adolescents (<18 years) a parent/guardian has not signed a consent form 2025-08-01T00:00:00.000Z 2027-02-28T00:00:00.000Z Intellectual (learning) disability or autism spectrum disorder Other This is an observational prospective cohort study recruiting people aged 14 years and over with a learning disability and/or autism who are considered at increased risk of psychiatric hospital admission (as identified by being rated red or amber on the Dynamic Support Register [DSR]). Participants will be recruited through NHS community mental health services across diverse areas of England. Family or paid carers may also take part. Participants will complete assessments at the start of the study and again at 6 and 9 months. Information will be collected from participants, carers and clinicians about psychiatric hospital admissions, mental health and behaviour, quality of life, unmet needs, use of health and social care services, medication and restrictive practices. Assessments can be completed face-to-face, by telephone or online. We would expect some people to receive a C(E)TR during follow-up and others will not. The main outcome is admission to psychiatric hospital during follow-up. Secondary outcomes include psychiatric symptoms (measured by the Moss-PAS Check), behaviour that challenges (Behaviour Problems Inventory - Short form), unmet need (CANDID-R), quality of life (WHOQOL-DIS), health-related quality of life (EuroQoL Five Dimensions), service use (contacts with health and social care using a modified version of the Adult Service Use Schedule), all of which will be completed by the participant with learning disability or autism. Family carers who are enrolled will complete measures of family carer distress (Kessler Psychological Distress Scale), and carer health-related quality of live (EQ-5D-5L). Clinicians providing care to recruited participants will provide information on participant symptom severity (using the Clinical Global Impression-Severity scale), participant health and social functioning (measured with Health of the Nation Outcome Scale, HoNOS), use of restrictive practices (i.e. Mental Health Act, Deprivation of Liberty Safeguards), psychotropic medication, and whether a C(E)TR was conducted. The main outcome will be psychiatric hospital admission during follow-up. Outcomes will be compared between participants who receive a C(E)TR and those who do not, to investigate whether C(E)TRs are associated with a reduced likelihood of hospital admission and better health and care outcomes. Other Not expected to be made available 7ec7713b-595d-402c-8112-c08062629892 51829bab-ef10-4763-8132-5e6692178f42 1c435748-e516-4e3f-a3f5-a034fa55a259 No Rory Sheehan https://orcid.org/0000-0002-4164-9661 Principal investigator Scientific Public

Institute of Psychiatry, Psychology & Neuroscience King's College London

London United Kingdom SE5 8AF +44 (0)20 7848 0002 rory.sheehan@kcl.ac.uk Public South London and Maudsley NHS Foundation Trust https://ror.org/015803449 Non-commercial National Institute for Health and Care Research http://dx.doi.org/10.13039/501100000272 89355835 true A randomised controlled trial to evaluate the effectiveness and cost-effectiveness of SAFE (Systemic Autism-related Family Enabling), an intervention for families of autistic children The SAFE Trial V1.0 To compare the effectiveness of SAFE + Treatment As Usual with Treatment As Usual alone for: 1. Longer-term family functioning: measured for the main caregiver in the family, using the SCORE-15 at 52 weeks. 2.1. Family functioning: measured for the main caregiver in the family, using the SCORE-15 at 52 weeks. 2.2. Family functioning: measured for the children aged 7 or above in the family using the Child SCORE-15 at 52 weeks at 22 weeks and 52 weeks. 3. Child-parent attachment: measured by the Coding of Attachment-Related Parenting for use in children with Autism (CARP-A) at 22 weeks and 52 weeks. 4. Anxiety and depression: measured by the Patient Health Questionnaire–9 (PHQ-9) and Generalised Anxiety Disorder–7 Questionnaire (GAD-7) score at 22 weeks and 52 weeks. 5. Frequency and severity of extreme behavioural outbursts (meltdowns) experienced by the autistic child: measured by the main caregiver using a monthly record. Also: To assess the cost-effectiveness of SAFE + Treatment As Usual with Treatment As Usual alone. Process evaluation objectives to: 1. Monitor how SAFE is delivered by the therapists (delivery fidelity). 2. Confirm the 'core components' that underpin the SAFE intervention (the logic model). 3. Produce a guide/toolkit in readiness for use after the trial, if SAFE is shown to be effective and cost-effective. Background and study aims Autism affects around 2% of people in the UK. Autistic children often struggle with communication and social interaction, and may experience distress or challenging behaviour. This can be hard for families, who often face poor mental health. Support after diagnosis is often not enough or suitable. A new support programme (called SAFE) has been developed with families of autistic children. SAFE includes proven approaches to help families manage the challenges of autism, such as so-called meltdowns. SAFE supports the whole family. Sessions are led by trained therapists and use talking, images, and play to explore autism-related challenges, behaviour, well-being, and coping. In the SAFE programme, there are two sessions where all the parents from 8 (+/-2) families meet with the therapists as a group, and five sessions where each family meets with the therapist separately. These seven sessions take about 20 weeks. This study will test whether SAFE improves family mental health and coping compared to usual care, and whether it is feasible and affordable for the NHS. Usual care is what families receive from the NHS or local authority Who can participate? Families including a child aged 3-16 years with a diagnosis of autism severity level 1 or 2, and a Primary Caregiver. If co-morbid conditions are present in addition to autism (e.g. Attention-Deficit Hyperactivity Disorder (ADHD), Obsessive-Compulsive Disorder (OCD), Eating Disorder (ED), epilepsy), autism must be the primary diagnosis. What does the study involve? All families will attend an initial meeting with a study researcher to confirm eligibility and to complete some questionnaires and carry out a Lego play activity. Two-thirds of the families taking part will be randomly selected to receive the SAFE support package and usual care. One third of families will just receive usual care. Usual care is the standard care that is offered locally. Taking part in SAFE involves attending two three-hour sessions for parents in a group with other parents of autistic children. There are also five two-hour sessions for each family, including children. All sessions take place in community rooms. Families will work with specially trained therapists. Follow-up meetings take place at 5 and 12 months after random selection, where all families will meet our researchers again. They will be asked to complete the same questionnaires as per the initial meeting and will do the same Lego activity. Families may also be invited to share their experience of the study in group feedback events. What are the possible benefits and risks of participating? Possible benefits: By participating, all families will enable this study to report on the effectiveness of SAFE versus usual care and whether SAFE is cost-effective. If SAFE is shown to be beneficial and value for money in the NHS, it may be provided to families in the future. Those families who receive the SAFE intervention in the trial may directly benefit from this support programme. Families may learn different ways of helping their family cope with the challenges associated with autism. Families attending the focus group may indirectly derive peer support from sharing time with other families in a similar situation. All families have access to usual care. At each trial location, there will be clinicians who can offer support as part of usual care, which may also be GP practices, to include those families who self-refer. In addition, families will be signposted to further support, including that provided by the NHS, local authority and third sector during the study. Possible risks: This is considered a low-risk study. Study procedures are not invasive and pose no significant risk to participants. A risk protocol will be initiated by research staff if a participant is perceived to exhibit new instances of suicide risk, i.e., expresses suicidal ideation, thoughts of self-harm, or thoughts of harm to others. Risk may present through responses to questionnaire items, or the participant may disclose information during study visits, e.g., SAFE sessions. The SAFE family sessions will involve discussing difficulties and may bring about emotions and strong feelings. The SAFE family therapists will be available to discuss any thoughts and feelings that participants have at the start of each session and in between sessions. There is a slight chance that the SAFE intervention sessions could lead to an initial increase in family disagreements as family members learn how to change the way they solve problems and talk with one another. However, the purpose of the intervention is ultimately to equip families with skills to handle these difficulties by learning how to change the way they solve problems and talk with one another, and the SAFE family therapists will be available to provide support and will be trained to handle any emerging problems Over 12 months, a participating family will attend baseline and follow-up visits and SAFE sessions (if randomised to SAFE), and a subset will be invited to take part in interviews and focus groups. To manage burden, flexibility for families has been embedded in the trial protocol, e.g. to allow for re-arrangement of SAFE sessions, and to have additional time at baseline and follow-up to complete trial assessments. Where is the study run from? 1. Devon Partnership NHS Trust (Sponsor site) 2. Peninsula Clinical Trials Unit (CTU) When is the study starting and how long is it expected to run for? August 2026 to March 2029 Who is funding the study? National Institute for Health and Care Research (NIHR) - Health Technology Assessment (HTA) Programme, UK. Who is the main contact? safe2.penctu@plymouth.ac.uk Family functioning and caregiver mental health the Systemic CORE-15 (SCORE-15) total score at baseline and at 22 weeks post-randomisation Family functioning the Systemic CORE-15 (SCORE-15) total score baseline and at 52 weeks post-randomisation Family functioning strengths and adaptability the strengths and adaptability dimension score of the Systemic CORE-15 (SCORE-15) baseline, 22 and 52 weeks post-randomisation Family functioning coping with difficulties and problem solving the coping with difficulties and problem-solving dimension score of the Systemic CORE-15 (SCORE-15) baseline, 22 and 52 weeks post-randomisation Family functioning communication and understanding the communication and understanding dimension score of the Systemic CORE-15 (SCORE-15) baseline, 22 and 52 weeks post-randomisation Family functioning from the child perspective for children aged 7 years or older the Child Systemic CORE-15 (Child SCORE-15) total score baseline, 22 and 52 weeks post-randomisation Child-reported family strengths and adaptability for children aged 7 years or older the strengths and adaptability dimension score of the Child Systemic CORE-15 (Child SCORE-15) baseline, 22 and 52 weeks post-randomisation Child-reported coping with difficulties and problem solving for children aged 7 years or older the coping with difficulties and problem solving dimension score of the Child Systemic CORE-15 (Child SCORE-15) baseline, 22 and 52 weeks post-randomisation Child-reported communication and understanding for children aged 7 years or older the communication and understanding dimension score of the Child Systemic CORE-15 (Child SCORE-15) baseline, 22 and 52 weeks post-randomisation Child-parent attachment the Coding of Attachment-Related Parenting for use with autistic children (CARP-A) score baseline, 22 and 52 weeks post-randomisation Primary caregiver anxiety and depression the Patient Health Questionnaire-9 (PHQ-9) score and the Generalised Anxiety Disorder-7 (GAD-7) questionnaire score baseline, 22 and 52 weeks post-randomisation Frequency and severity of extreme behavioural outbursts experienced by the autistic child participant a non-validated measure a monthly time point, from baseline to 52 weeks post-randomisation Resources required to provide the SAFE intervention participant-level intervention resource use data collected time points during the course of the intervention Health-related quality of life and quality-adjusted life years (QALYs) for adult participants QALYs derived from the EQ-5D-5L at baseline, 22 and 52 weeks post-randomisation Health-related quality of life and quality-adjusted life years (QALYs) for child participants QALYs derived from the Child Health Utility 9 Dimensions (CHU-9D) baseline, 22 and 52 weeks post-randomisation, with proxy completion by the primary caregiver for children aged 5 to 6 years and the CHU-9D proxy version for children under 5 years of age Capability wellbeing and years of full capability (YFCs) YFCs derived from the ICEpop CAPability measure for Adults (ICECAP-A) baseline, 22 and 52 weeks post-randomisation Health, social care and wider societal resource use a bespoke Resource Use Questionnaire informed by previous RUQs and co-developed with the PPI group at baseline, 22 and 52 weeks post-randomisation Ethics approval required London - Camden & Kings Cross Research Ethics Committee

2 Redman Place, Stratford

London United Kingdom E20 1JQ 26/LO/0247 10.1186/ISRCTN89355835 343024 CPMS: 62076, NIHR: 167788 343024 62076 167788 Interventional Randomized controlled trial Blinded (masking used) Active Parallel Treatment Not applicable Treatment 2029-03-31T00:00:00.000Z United Kingdom England Prestwich Hospital

Bury New Road Prestwich

Manchester England M25 3BL South London and Maudsley NHS Foundation Trust

Sunshine House 27 Peckham Road

London England SE5 8UH RXM14@2.16.840.1.113883.2.1.3.2.4.18.48 Wonford House Hospital

Dryden Road

Exeter England EX2 5AF North East London NHS Foundation Trust

West Wing C E M E Centre Marsh Way

Rainham England RM13 8GQ RAT@2.16.840.1.113883.2.1.3.2.4.18.48 Leicestershire Partnership NHS Trust

Room 100/110 Pen Lloyd Building County Hall Leicester Road

Leicester England LE3 8RA RT5@2.16.840.1.113883.2.1.3.2.4.18.48 Central and North West London NHS Foundation Trust

Trust Headquarters 350 Euston Road Regents PLACE

London England NW1 3AX RV3@2.16.840.1.113883.2.1.3.2.4.18.48 false Families must satisfy all the following criteria to be enrolled in the study: 1. Family includes autistic child, aged 3-16 years*. 2. Diagnosis of autism, severity level 1 or 2 (in accordance with DSM-5). 3. If other diagnoses are present (e.g., ADHD, OCD, ED), autism must be the primary diagnosis. 4. Family are willing and able to comply with study requirements. *In families with more than one eligible child, only one can be the family index case. Mixed 3 Years 65 Years All 494 0 Families who meet any of the following criteria will be excluded from study participation: 1. Serious concomitant illness in the child or family, or other circumstances affecting compliance with study requirements. 2. Risk to the safety of research staff*. 3. Family currently or due to take part in family therapy-based intervention during study participation. 4. Individual family members already taking part in the SAFE trial as part of another family unit. 5. Unable to understand or communicate in English**. *Examples of risk: Violent behaviour causing injury that requires treatment, or a family member who has a serious infectious disease. **English language: This is due to the delivery of the SAFE intervention being in English. Those who speak English as an additional language will be eligible to take part, but will be encouraged to attend appointments with a conversational partner if necessary to assist with study delivery. 2026-08-01T00:00:00.000Z 2028-03-31T00:00:00.000Z Diagnosis of autism; if other diagnoses are present (e.g., ADHD, OCD, ED), autism must be the primary diagnosis Mental and Behavioural Disorders CHOICE OF STUDY DESIGN AND METHODOLOGY This study has been informed by a successful feasibility randomised controlled trial. The study has been designed to compare the effectiveness of intervention against control as would be observed in routine practice, in a rigorous randomised controlled trial (RCT). This is a definitive RCT of SAFE+TAU (intervention) versus TAU alone (control) with an internal pilot and an embedded economic evaluation and process evaluation, to be conducted in secondary care NHS Trusts in the UK. RESEARCH PROTOCOL Potential eligible families will first hear about the study either from their clinical team or via advertising in trial locations. Clinical pathway: Potential eligible families will be provided with participant information documents (PID) and a letter of invitation, either in-person during a routine appointment, or via email or post by a member of the direct care team. The PID will be supplemented by a video explaining the study developed in collaboration with Patient and Public Involvement (PPI) study members. A main caregiver (Primary Caregiver) will be defined for the study, and they will be asked to explain the study information to younger children in a way which is appropriate for their child. If approached in person, potential participant families will be asked if they wish to receive a follow-up call from a member of the research team. If they agree, this call will take place after the family has had sufficient time to consider participation. Usually, this will be at least 24 hours after provision of the study information, but may be sooner if the family wishes. If the family does not wish to receive a follow-up call, they will be advised that, should they reconsider, they can use the information on the PID to contact the research team directly, or self-refer via the SAFE webpage on the PenCTU website. A member of the direct care team may contact families directly to ascertain interest if they do not respond to the letter of invitation sent via email or post. Community pathway: The study will be advertised via community channels in our trial locations. Appropriate means for approaching local community members will be established with our PPI networks, e.g. posters and leaflets in community venues and sharing study information via social media. Families will be invited to self-refer to the research team, either by using the research team contact details provided in the PID or via an expression of interest form on the SAFE webpage. For families whose first language is not English: Translated versions of the PID can be provided on request. Such families will be encouraged to bring a 'conversational partner' to all study visits; this is a trusted person who speaks both the family's native language and English. Conversational partners may also assist families in other contexts, e.g. families with hearing impairments or single parents who would benefit from additional support in sessions. Note that all participant-reported outcome measures must be completed in English and by the participant to ensure the validity of such measures. Baseline visit and consent: Initially, eligible and amenable families will be invited to attend a face-to-face visit with the research team at a suitable local venue at the trial location itself or in the community. For community referrals, eligibility must be confirmed via diagnostic letters and reports held by the family. If eligible and willing to participate, a delegated member of the research team will obtain informed consent from the adult family members and continue with the baseline assessments. Children aged under 16 years will be given the option of completing a separate study-specific assent form if they wish. Where the child does not provide assent, the researcher will work with the Primary Caregiver to address the child's concerns. The composition of the family will be defined at this visit, including confirming the Primary Caregiver. All family members participating in the study must attend the baseline visit. The minimum requirement for each family unit is the autistic child and the Primary Caregiver, and the maximum number is 7 family members. Participants will be given the option to complete self-report measures digitally (e.g., direct entry into the survey or the MyCap app) or using paper CRFs, which will be uploaded to the study database by the researcher. Baseline data collection (approximately 2 hours): Following receipt of informed consent/assent, the family history and demographic data of all family members will be collected. At the same visit, the researcher will support the participant family to complete the following baseline assessments: Systemic CORE 15 (SCORE-15), Child SCORE-15, Patient Health Questionnaire - 9 (PHQ-9), Generalised Anxiety Disorder-7 Questionnaire (GAD-7), Coding of Attachment-Related Parenting for use in children with Autism (CARP-A), (EQ-5D-5L), Child Health Utility 9 Dimensions (CHU-9D), ICEpop CAPability (ICECAP-A), Resource Use Questionnaire (RUQ). Primary caregivers will also be given a template to record the monthly incidence of meltdowns. All assessments should be completed during a single visit. If this is not possible, families will be given the option to complete the remaining assessments either online or using paper booklets within two weeks of the baseline visit. If additional support is required, the researcher may schedule a second in-person study visit with the family. In all cases, the primary outcome measure (SCORE-15) must be completed by the Primary Caregiver at the first in-person visit. Randomisation: Once twelve (+/-3) families have consented and completed the baseline assessments, they will be randomised en bloc to receive intervention or control. The randomisation sequence will be in place and will have been generated by a member of the Peninsula Clinical Trial Unit (PenCTU) statistics team and implemented through a secure web-based system on REDCap, ensuring allocation concealment. The system will be developed in conjunction with a statistician independent from the trial team and will use random permuted blocks and stratified by recruiting location. The PenCTU data management team will run checks before and during the trial to verify the integrity of the randomisation system. Randomisation en bloc is necessary as the intervention comprises group sessions for parents. Families are randomised in a 2:1 (SAFE+TAU: TAU) ratio. Advantages of 2:1 allocation include: an increased appeal for families deciding whether to consent to randomisation based on PPI feedback; minimal reduction in statistical power for between-groups comparisons in a full-scale evaluation. Post-randomisation: All participating families will receive Treatment As Usual for the duration of the study (Weeks 1 to 52). Assessments and intervention sessions for the SAFE group (Weeks 1 -20): At an introductory visit, which is expected to take approximately 2 hours, the Family Therapist will explain the intervention schedule and answer any questions the family may have. The Family Therapist will conduct the Parent Development Interview (PDI) with each parent in preparation for the SAFE therapy sessions. Where the Primary Caregiver is not a parent, the PDI will be conducted with the PC instead. The PDI is an audio-recorded interview consisting of 20 items and takes approximately 40 minutes to complete. The full interview schedule provides background information on the relationship between the Primary Caregiver and the child, which will inform the SAFE sessions. If both parents are participating, they will both be interviewed. The Family Therapist will also check during this visit that the family can attend the next scheduled group therapy session, explain the family reflection activity and answer any questions the family may have. The Family Therapist will also provide a schedule of the subsequent SAFE sessions scheduled for the relevant cohort to the family (two multi-parent group sessions and five individual family therapy sessions). The SAFE intervention consists of two sessions with all of the parents as a group (3 hours per session) and five sessions as an individual family (2 hours per session). The SAFE intervention can be delivered in 13 weeks, but the sessions are built in flexibility as standard practice to account for family availability and rescheduling. 20 weeks will be allocated for the intervention. The aim is to schedule the first SAFE intervention session within two weeks of randomisation, but this will depend on family availability and time to recruit a full cohort at each trial location. At a minimum, the autistic child and Primary Caregiver from each family must attend each intervention session. Where this is not possible, the family therapy session (including group sessions) must be rearranged. Individual catch-up sessions may be arranged for other family members who are unavailable to attend a session, though best endeavours should be made for all family members (as defined at the baseline visit) to attend every session. The number of sessions a family may reschedule will be at the Family Therapist's discretion, based on family circumstances, motivation and levels of problems/distress. Assessments for all families (Weeks 22 and 52): All families will be followed up at 22 weeks and 52 weeks via a face-to-face visit with a researcher. The visit will take place in a community venue or at another setting, such as a venue provided by the trial location, if convenient and acceptable to both the family and the researcher. All outcome measures conducted at the baseline visit will be repeated at both follow-up visits, with support from the researcher. Families will be reminded to bring their diary of behavioural meltdowns to each follow-up visit. The same arrangements as described for the baseline visit will be in place, i.e., prioritising competition of the primary outcome at the visit and arranging a second visit with support as necessary to complete the full set of measures. Separately, a subset of families will be invited to take part in focus groups. Families from both arms of the study will be approached to take part in a focus group by the researcher via a verbal discussion and provision of a Participant Information Sheet. Informed consent will be obtained by the suitably qualified member of staff prior to any data collection. The aim of the focus group is to hear about the families' experiences of being in the SAFE study (what has changed for the family, what was good, what was not good, and what is next for the family) Focus groups at Week 22 will be conducted in person at an acceptable and secure venue by the local researcher at each trial location. One focus group will be with the second cohort receiving the intervention to represent earlier delivery, and one focus group with the sixth (or final) cohort receiving the intervention to represent later delivery. This is 18 focus groups in total. Each focus group will consist of 6-10 families and last up to 3 hours. One focus group will be conducted at each location by the local researcher following the week 22 post-randomisation visit of the sixth (or final) cohort, inviting all families who have participated in the control arm across all previous cohorts at each location (to compensate for the 2:1 randomisation). This is 6 focus groups in total. Each focus group will consist of 6-10 families. Following the week 52 post-randomisation visit of the 6th (or final) cohort at one trial location, two separate focus groups will be conducted for the intervention and control arm. Invitations will extend backwards through the cohorts to recruit 6-10 families still engaged in the study. All in-person and remote data collection for focus groups and interviews will be digitally recorded and transcribed verbatim. Interviews with families who decline participation: When an eligible family declines to participate in the study, the primary caregiver will be invited by the local researcher to engage in a short, focused telephone interview (~10 mins) to discuss their decision not to participate, and the findings will be reported to the Trial Management Group for consideration. Interviews with families who withdrew participation: When a family withdraws from the study, the local researcher will make a phone call to invite the primary caregiver to engage in a short, focused telephone interview (~10 mins) with them to discuss the reasons for their decisions, and how the main trial can be designed to address these issues. The findings will be reported to the Trial Management Group for consideration. PROCEDURES TO DETECT POSSIBLE RESEARCHER EFFECTS: 1) Blinding The coordinating trial management team will be blinded to treatment allocation. It's not possible to conceal from families whether they will receive intervention or control: the trial is not blinded to participants. Family therapists will also be aware of the participant's allocation to intervention or control, and they will be discouraged from communicating with other members of the local research team about this. Family therapists will be responsible for scheduling intervention sessions for those allocated to intervention to protect the blind as much as possible from the researchers (assessors) undertaking the follow-up assessments at weeks 22 and 52. Families will be asked not to reveal their allocation to the assessor, but it is possible that this will occur. The success of outcome assessor-blinding will be evaluated at each follow-up visit by asking assessors to record the treatment group to which they think a participant has been allocated, and any cases of inadvertent unblinding, in the case report form. The data collection at all follow-up assessments is largely self-reported by the participant families, which reduces the possibility of introducing reporter bias for these assessments. The CARP-A is an observational measure; therefore, to minimise bias, a sub-sample of videos of the participant families will be viewed and assessed by a Research Fellow in the central team at the University of Plymouth. PenCTU will hold the key to the allocation. The trial statistician responsible for undertaking the analyses will be blinded to allocated groups at least until the statistical analysis plan is finalised and signed off by an independent statistician. An unblinded statistician will assist with the preparation of the Data Monitoring and Ethics Committee report and perform treatment allocation balance checks. Video analysis of intervention sessions will be used for supervision and also for oversight of therapist adherence by designated supervision therapists. The Therapist Checklist Questionnaire (TCQ), assessing protocol adherence, ease of delivery, and therapist confidence, will be completed by SAFE family therapists after every SAFE intervention session. The Helpful Aspects of Therapy (HAT) questionnaire will be completed by families after each SAFE session, capturing satisfaction with sessions and contributing to fidelity checking. SAMPLE SIZE FOR THE PROJECT: Families will be recruited via six trial locations and associated community pathways. The target sample size is 494 families (330 in the intervention group and 164 in the control group). This has been calculated by the trial statisticians, based on available literature, including the SAFE Feasibility Study, to detect a minimal clinically important difference of three on the primary outcome measure. In brief, the sample size calculation takes into account a possible multi-parent group effect in the intervention group, and loss to follow-up in the trial. The sampling strategy for the focus groups has been determined by the process evaluation and implementation co-applicants (TT and JG) in conjunction with the Chief Investigator, taking account of participant burden and researcher capacity. Discussions with potential participating locations have informed the planned recruitment rate for the trial. TIMETABLE FOR THE STAGES OF THE RESEARCH: The project started in October 2025 and lasts 48 months as follows: set-up in months 1-9; recruitment, intervention and follow-up in months 10 to 32 months, analysis and write-up in months 41-48. PLANNED INTERIM ANALYSES/REPORTS: An internal pilot, lasting for 6-months after recruitment commences, will be conducted. Pre-defined progression criteria for the internal pilot will be used to determine whether the trial will progress. The internal pilot report will be submitted to the funder. ADVICE FROM STAKEHOLDERS: PPI contributors were consulted throughout. Feedback and insights were provided at the design stage on: all participant-facing documents, including the study logo, tone and language used (especially related to autism) and presentation of documentation (colourways); burden of outcome measures; topic guides for interviews and focus groups. Behavioural The datasets generated during and/or analysed during the current study are/will be available upon request from the Devon Partnership NHS Trust (tobit.emmens@nhs.net). - The type of data: Anonymised individual participant data and supplementary files (e.g. data dictionaries, blank data collection forms, analysis code) - When the data will become available and for how long: After the trial has been reported, for 20 years - By what access criteria data will be shared, including with whom, for what types of analyses, and by what mechanism: Requestors whose proposed use of the data has been approved by the Chief Investigator and Sponsor, under and an appropriate data sharing agreement - Whether consent from participants was obtained: Participants have consented to the sharing of their anonymised data - Comments on data anonymisation: Participants will be identified in all study-related documentation by their study number and initials, and all data collected and analysed will be pseudonymised by the use of this unique identifier. Audio data will be transcribed, pseudonymised and deleted as soon as is practicable - Any ethical or legal restrictions: None - Any other comments): None Available on request Protocol

b51fcfce-a077-4ef4-951c-5001a9527325 10aa5f7d-2783-45c5-930c-a4f2829e2086 7562992f-c3f7-4f52-9564-ebe30cb3d724 de104b09-5db8-4e3f-b9e5-c7c38397b512 Yes Protocol file ISRCTN89355835_Protocol_V1.0_20Feb2026.pdf 1c3a5381-9cf6-4437-992a-74d797e2411e true application/pdf 1072936 fcba472a82165d0024d058c6e11878f6 Protocol file ISRCTN89355835 SA001_SAFE2 Protocol Version 1.1_02 Jul 2026_clean.pdf 91ce908d-2330-4278-bf90-746080ae4bd2 true application/pdf 1281151 102c6fa68e019ea997a632d43c33d25b Kayle-Anne Sands Public Scientific

Peninsula Clinical Trials Unit Faculty of Health University of Plymouth Express Diagnostics 6 Research Way Plymouth Science Park Derriford

Plymouth, Devon United Kingdom PL6 8BU - safe2.penctu@plymouth.ac.uk Public Rebecca Stancer https://orcid.org/0000-0001-8152-7880 Principal investigator

School of Law, Humanities and Social Sciences, University of Plymouth, Room 108, 5 Portland Villas

Plymouth United Kingdom PL4 8AA +44 01752600600 rebecca.stancer@plymouth.ac.uk Public Devon Partnership NHS Trust Hospital/treatment centre https://ror.org/04fkxrb51 Non-commercial National Institute for Health and Care Research http://dx.doi.org/10.13039/501100000272 10087117 true A multi-centre effectiveness and cost-effectiveness superiority randomised controlled trial of a group-based intervention for family carers of people living with dementia, called Empowered Conversations, compared to treatment as usual Primary objectives are: (1) Assess the effectiveness of EC in reducing carer stress ([Perceived Stress Scale [PSS] at 26-weeks post-randomisation) compared to a TAU Control; (2) determine the cost-effectiveness of EC. Secondary objectives are: (3) Assess the effectiveness of EC on secondary outcomes: anxiety and depression [Hospital Anxiety and Depression Scale (HADs)]; relationship strain [Dyadic Relational Scale]; quality of Life [Carer QOL and carer perceived rating for person living with dementia)]; Carer goals [Goal-based outcome measure]; Activities of daily living; Peer Support; Communication at 16 and 26 weeks post-randomisation (4) Assess the effectiveness of EC in reducing carer stress (PSS) at 16 weeks, (5) Assess fidelity to the intervention protocol using a fidelity checklist that is observer and facilitator rated, (6) Provide the first examination of whether effectiveness is different in the in-person version compared to the online version of EC, (7) Explore whether effectiveness varies according to key carer status factors (e.g. providing ‘full-time’ vs ‘part-time’ support; and an estimate of symptom severity of the person living with dementia), (8) Provide initial psychometric properties and analysis of the Peer Support measure, (9) Provide the first full evaluation of safety indices in a definitive clinical trial of EC, (10) Provide initial acceptability data on the adaptations made to EC, and additional training for facilitators, to make EC more accessible to minoritised (global majority) communities. Background and study aims There are 700,000 family carers for people living with dementia in the UK. Sixty-four percent of carers who are unpaid in England say they have limited support for the range of psychological and social needs they experience. It can be difficult to keep communicating well due to thinking and memory changes that arise when someone is living with dementia. This can lead to frustration, low-mood and stress for both people living with dementia and their carers. The 6-session Empowered Conversations (EC) course is designed to enable carers to establish and maintain good communication and relationships with those they support. Course facilitators are trained to provide specific communication techniques, ways of managing conflicts and working with difficult emotions. EC can be delivered in person or online. The main goal of the study is to find out if EC, a group-based support program for people who care for someone with dementia, helps and is worth the cost. The study aims to: (1) see how well EC works; (2) find out if it provides good value for money. Who can participate? Current unpaid or family carer for someone living with dementia (any subtype or severity) in the community. Participants should provide emotional or practical support at least weekly, be aged 18 or over, and have the capacity to give informed consent for the study. Either the carer or the person living with dementia that they are supporting should live within the boundaries of the recruiting Trusts. What does the study involve? During the first appointment, participants will be asked to complete some brief demographic questionnaires that should take about 15-20 minutes. Participants will be able to complete these online, over the phone, or at home. During the second appointment, participants will be asked to complete several questionnaires that should take about 45- 60 minutes. Participants will be able to complete these online, over the phone, or at home. Participants will then be randomised to either receive the six-week EC course during the study’s duration or continue as usual. Participants who are selected to continue as usual will be offered to receive the online EC course after the study has finished. Approximately 4 and 6 months after the first appointment, participants will be invited to complete further questionnaires. Participants will be able to complete these online, over the phone, or at home. What are the possible benefits and risks of participating? The anticipated benefits for carer trial participants are improvements in carer psychological well-being, communication and quality of life. Outcomes from our feasibility trial indicate that carers experience significant reductions in stress and improvements in communication following the EC course. Qualitative data suggests that these improvements in carer stress and communication have an impact on the well-being of the person living with dementia that they are supporting. It is not anticipated that there are any significant risks or burdens for trial participants. Although talking about the problems of being a carer could be upsetting, in our experience, carers do not find it distressing and usually find it helpful. Some participants may find completion of questionnaire measures burdensome; the researchers will provide practical (splitting sessions up) and emotional support (distress management) if required. Where is the study run from? Lancashire Clinical Trials Unit, University of Lancashire (UK) When is the study starting and how long is it expected to run for? April 2026 to June 2028 Who is funding the study? National Institute for Health and Care Research (NIHR), Research for Patient Benefit (RfPB) Programme, UK. Who is the main contact? Dr Lydia Morris lydia.morris@manchester.ac.uk Stress the Perceived Stress Scale baseline, 16 weeks and 26 weeks Perceived support from other group members the Peer Support Questionnaire baseline, 16 weeks and 26 week Relationship strain the Dyadic Relationship Scale (Caregiver) baseline, 16 weeks and 26 week Specific goals that the carer has for the course the Goal-Based Outcome Measure baseline, 16 weeks and 26 week Carer perceptions of communication the Carer Communication Questionnaire baseline, 16 weeks and 26 week Quality of life (carer) the C-DEMQOL questionnaire baseline, 16 weeks and 26 week Quality of life (person living with dementia) the DEMQOL-Proxy questionnaire baseline, 16 weeks and 26 week Anxiety and depression the Hospital Anxiety & Depression Scale (HADS) baseline, 16 weeks and 26 week Ability of someone with dementia to carry out daily activities, such as dressing and preparing food the Bristol Activities of Daily Living Scale (BADLS) baseline Demographics the Demographic questionnaire baseline Health-related quality of life EQ-5D-5L tool baseline, 16 weeks and 26 weeks Hospital, primary, community and social care use the Healthcare Service Use questionnaire baseline, 16 weeks and 26 weeks Harms and adverse effects adverse event reports throughout the study and Adapted Adverse Effects of Therapy Checklist 16 weeks and 26 weeks Ethics approval required East of England - Cambridge South Research Ethics Committee

Equinox House, City Link

Nottingham United Kingdom NG2 4LA 26/EE/0022 10.1186/ISRCTN10087117 346849 CPMS: 63791, NIHR: 208874 346849 63791 208874 Interventional Randomized controlled trial Blinded (masking used) Active Parallel Treatment Not applicable Treatment 2028-06-30T00:00:00.000Z United Kingdom England Greater Manchester Mental Health NHS Foundation Trust

Prestwich Hospital Bury New Road Prestwich

Manchester England M25 3BL RXV@2.16.840.1.113883.2.1.3.2.4.18.48 Pennine Care NHS Foundation Trust

225 Old Street

Ashton-under-lyne England OL6 7SR RT2@2.16.840.1.113883.2.1.3.2.4.18.48 Lancashire & South Cumbria NHS Foundation Trust Hq

Sceptre Point Sceptre Way Bamber Bridge

Preston England PR5 6AW RW501@2.16.840.1.113883.2.1.3.2.4.18.48 North East London NHS Foundation Trust

West Wing C E M E Centre Marsh Way

Rainham England RM13 8GQ RAT@2.16.840.1.113883.2.1.3.2.4.18.48 false 1. Current unpaid or family carer for someone living with dementia (any subtype or severity) in the community 2. Provide emotional or practical support at least weekly 3. Aged 18 or over 4. Have the capacity to give informed consent for the study 5. Either the carer or the person living with dementia that they are supporting, and live within the boundaries of recruiting Trusts Mixed 18 Years 100 Years All 336 0 1. Unable to provide informed consent 2. Currently enrolled in a concurrent non-pharmacological (psychosocial intervention) carer research study 3. Caring for someone living with dementia in a Nursing or residential care home 4. The person living with dementia being cared for is receiving palliative care or considered to be in the last six months of their life 2026-04-15T00:00:00.000Z 2027-07-31T00:00:00.000Z Specialty: Social Care, Primary sub-specialty: Social Care; Health Category: Neurological; Disease/Condition: Organic, including symptomatic, mental disorders Mental and Behavioural Disorders The trial will recruit 336 participants to compare two approaches to treatment. Two-thirds of the participants (224 people) will receive both a course called 'Empowered Conversations' and the standard care they usually get (called Treatment-As-Usual, or TAU). The other third will receive just the standard care. This selection is chosen at random by a computer program, with the research team having no input on what someone receives. Empowered Conversations (EC): EC is group-based and delivered across six weeks. It is designed to enable carers to establish and maintain good communication and relationships with those they support. Course facilitators are trained to provide specific communication techniques, ways of managing conflicts and working with difficult emotions. EC can be delivered in person or online. Treatment-As-Usual (TAU): EC will be compared with TAU, which is likely to be limited in terms of support, but can include support from services (e.g. Age UK or Alzheimer’s Society) in some cases. Given that there is rarely a specific carer service or pathway offered within the NHS, the nature of this support will vary. Participants allocated to TAU will be offered the EC course following completion of their participation in the trial. Behavioural The datasets generated during and/or analysed during the current study will be stored in a publicly available repository. In line with NIHR guidelines, fully anonymised quantitative data will be deposited in a public repository (https://figshare.com/). This is a publicly available and searchable platform where it will be permanently stored. Researchers at other institutions and others can access the anonymised data directly from the repository and use it for further research or to check the analysis and results. Stored in publicly available repository Protocol

5be85efe-a9cc-4642-8aa0-8a458c5f4640 c076b5c9-47b4-4f60-93bc-37a97b66b6a4 84013834-8384-439a-877e-6f829b338292 698a5d00-7a75-4674-b41c-2f1615d48843 Yes Protocol file 49188_Protocol_v1.1_23Feb2026.pdf d755b954-bbf8-4b61-9129-16d778137d36 true application/pdf 681595 1273a151793d8df9a4052cb8be2fdcd7 Lydia Morris https://orcid.org/0000-0002-3337-8144 Scientific Principal investigator

Chief Investigator, Division of Psychology and Mental Health, School of Health Sciences, University of Manchester, Booth Street East Building, Booth Street East

Manchester United Kingdom M13 9PL +44 01613061194 lydia.morris@manchester.ac.uk Public Egle Saviciute Public Scientific

Trial Manager, Lancashire Clinical Trials Unit, University of Lancashire

Preston United Kingdom PR1 7QS - LCTUEC@lancashire.ac.uk Public University of Manchester Hospital/treatment centre https://ror.org/027m9bs27 Non-commercial National Institute for Health and Care Research http://dx.doi.org/10.13039/501100000272 12117573 true Feasibility of a randomised controlled trial to compare an adapted online parent-led treatment to treatment as usual for preadolescent children with obsessive compulsive disorder (OCD) a. Establish the feasibility of (a) the novel intervention and (b) a future definitive non-inferiority RCT comparing the clinical outcomes and cost-effectiveness of OSI for OCD to usual treatment b. Conduct a process evaluation to explore (a) the implementation and acceptability, (b) mechanisms of impact, and (c) contextual factors that affect delivery, engagement, and outcomes for OSI for OCD to optimise the design of a future definitive non-inferiority trial RCT and subsequent wider implementation of OSI for OCD, if indicated. Background and study aims Childhood Obsessive-Compulsive Disorder (OCD) is a serious mental health condition that often starts around the age of 10 years old and affects up to 3% of preadolescent children worldwide. Cognitive Behavioural Therapy (CBT), including Exposure and Response Prevention (ERP), is a current treatment that helps many preadolescent children with OCD; however, current treatments are often long (requiring more than 10 hours of specialist therapist support), which can limit access to care. Online Support and Intervention (OSI) is a brief online, therapist-supported, parent-led CBT programme that has the potential to increase access to support for affected families. OSI only requires around 3 hours of direct therapist support and can be delivered by trained non-specialist therapists. OSI has been evaluated for childhood anxiety problems and is acceptable to families and therapists, effective, and likely to be cost-effective compared to usual treatment (mostly CBT) in services. OSI has been co-adapted for OCD by working with parents of children with OCD, children with OCD, and clinicians to ensure that the OSI-OCD is acceptable, relevant, and appropriate for families. This study will be a preliminary evaluation of OSI-OCD. This project will test the feasibility of OSI adapted for parent/carers of preadolescent children (aged 5 – 12 years old) with OCD, and a future large Randomised Controlled Trial (RCT) to test whether OSI for OCD is non-inferior to (i.e., no worse than) usual treatment in services. This feasibility RCT will establish the likely recruitment rates, the number of participants who complete treatment, the number of participants who take part in the research follow-ups, and help us to describe what ‘usual treatment’ looks like in routine clinical services, and identify suitable clinical, daily functioning, and cost-effectiveness measures. The study will also explore the clinical outcomes in the OSI group at 20- and 32-week follow-ups (i.e., whether OSI for OCD appears to help children overcome OCD), explore what key stakeholders (e.g., parents, children, therapists) think of the treatment and trial procedures, and describe any negative effects of the treatment. A ‘process evaluation’ will be conducted, which is a way of taking a closer look at how an intervention is being carried out. This evaluation will explore how OSI for OCD can be implemented into clinical services, how the treatment might bring about change for families, and factors affecting treatment delivery, engagement, and outcomes for OSI for OCD to inform the design of a future RCT and potential wider use of OSI for OCD. Who can participate? Children aged between 5 and 12 (inclusive) years who have OCD (confirmed by the research team) and their parent/carer(s) from approximately 6 mental health services that provide treatment on behalf of the National Health Service (NHS). What does the study involve? Eligible participants will be randomly assigned to one of two groups: one group will receive the new OSI for OCD treatment, and the other will receive the usual treatment for OCD. Measures will be collected at baseline, 20 weeks and 32 weeks post-randomisation. Additionally, parent-reported session-by-session measures will be collected for participants (i.e., parents and their children) randomised to OSI for OCD. Interviews with some parents, children, therapists, clinical supervisors, service leads and commissioners involved in the trial will help to inform the process evaluation. What are the possible benefits and risks of participating? Benefits: Both treatments could be helpful for children with OCD, but it is unknown which treatment works best or if they work equally well. That’s why this research is being done. By taking part, participants will be helping the research team understand whether this treatment is feasible and acceptable for helping children to overcome OCD, and their participation will contribute to improving treatment options for others in the future. Risks: The parent and their child will be asked to complete some additional questionnaires that they wouldn’t normally do as part of usual care. These are to gather information about the child’s difficulties and the impact these difficulties have on their life. Some of the questions in the interviews or questionnaires may ask about difficult topics, such as the child’s thoughts and feelings. While these questions are similar to those asked in clinical care, the research team understands they might be upsetting. The research team will monitor the parents' and children's responses during these assessments and, if signs of significant distress are noticed, the team will contact the parent to check in. If necessary, and with the parent’s agreement (or sooner if there are concerns about safety), the team may contact the child’s clinical team. If the parent or child feels uncomfortable or distressed at any point, they can contact their therapist or the research team, and support will be provided. They can also choose to stop answering questions or leave the study at any time without affecting the child’s future care. Taking part in the study will require the parent and child to spend extra time completing interviews and questionnaires and participating in treatment sessions. These additional tasks might take time away from other activities or routines, but the research team will work to make the process as convenient as possible. The research team does not expect any harm or significant risks to come from taking part in the study. All research team members have undergone criminal record checks and have been approved by the University of Oxford to work with children. If at any point the parent feels that participating in the study is not right for them, they are free to withdraw with no negative impact on the child’s care or treatment. Where is the study run from? This study is sponsored by the University of Oxford, and is being run by the Oxford Psychological Interventions for Children and adolescents (TOPIC) research group, based in Experimental Psychology, UK. When is the study starting and how long is it expected to run for? September 2025 to June 2027. Who is funding the study? The Medical Research Council (MRC). Who is the main contact? Dr Chloe Chessell (Chief Investigator), Postdoctoral Researcher and Fellow at The Oxford Psychological Interventions for Children and adolescents (TOPIC) research group, based in Experimental Psychology, chloe.chessell@psych.ox.ac.uk Trial feasibility willingness of participants (parents and their children) to be randomised throughout study OCD symptom severity Children’s Yale-Brown Obsessive Compulsive Scale (CY-BOCS) (parent and child report) baseline, 20 weeks post randomisation, and 32 weeks post randomisation 1. Anxiety disorders and OCD are measured using the Anxiety Disorder Interview Schedule (ADIS-C and ADIS-P) at screening, 20 weeks post-randomisation, and 32 weeks post-randomisation 2. OCD symptom severity is measured using the Children’s Yale-Brown Obsessive Compulsive Scale (CY-BOCS) at baseline, 20 weeks post-randomisation, and 32 weeks post-randomisation 3. OCD symptom severity is measured using the Obsessive Compulsive Inventory (OCI-CV-R) at baseline, 20 weeks post-randomisation, and 32 weeks post-randomisation 4. OCD symptom severity is measured using the Obsessional Compulsive Inventory (ChOCI-R-P) at baseline, at the start of each OSI-OCD module, and at 20 weeks and 32 weeks post-randomisation 5. Parental stress is measured using the Parental Stress Scale (PSS) at baseline, 20 weeks post-randomisation, and 32 weeks post-randomisation 6. Health-related quality of life for parents is measured using the EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L) at baseline, 20 weeks post-randomisation, and 32 weeks post-randomisation 7. Health-related quality of life in children and young people is measured using the EuroQol 5-Dimension Youth 3-Level questionnaire (EQ-5D-Y-3L) and Child Health Utility 9D (CHU-9D) at baseline, 20 weeks post-randomisation, and 32 weeks post-randomisation 8. Health and social care resource use is measured using the Client Service Receipt Inventory (CSRI) at baseline, 20 weeks post-randomisation, and 32 weeks post-randomisation 9. Parents’ beliefs about treatment credibility and expectations of improvement are measured using the Credibility and Expectation of Improvement Scale – Parent report (CEI) immediately post-randomisation and at 20 weeks post-randomisation 10. Therapists’ beliefs about treatment credibility and expectations of improvement are measured using the Credibility and Expectation of Improvement Scale – Therapist report (CEI) immediately post-randomisation and at 20 weeks post-randomisation 11. Family accommodation of obsessive–compulsive symptoms is measured using the Family Accommodation Scale for Obsessive-Compulsive Disorder – Parent Report (FAS-PR) at baseline, 20 weeks post-randomisation, and 32 weeks post-randomisation 12. Parent-reported OCD-related interference is measured using the Children’s Obsessive Compulsive Impact Scale – Revised, Parent version (COIS-R-P) at baseline, 20 weeks post-randomisation, and 32 weeks post-randomisation 13. Child-reported OCD-related interference is measured using the Children’s Obsessive Compulsive Impact Scale – Revised, Child version (COIS-R-C) at baseline, 20 weeks post-randomisation, and 32 weeks post-randomisation 14. Parents’ knowledge and confidence to help their child overcome OCD are measured using 3 items at the start of each OSI-OCD module and at 20 weeks and 32 weeks post-randomisation 15. Parents’ perception of their child’s learning and coping ability is measured using 2 items at the start of each OSI-OCD module and at 20 weeks and 32 weeks post-randomisation 16. Child anxiety and depression symptoms are measured using the Revised Child Anxiety and Depression Scale – Parent version (RCADS-P) with the full scale completed at the start of OSI-OCD modules 0, 8, and 9, and the OCD subscale completed at the start of modules 1–7 17. Child functioning and wellbeing are measured using the Outcome Rating Scale (ORS) at the start of each OSI-OCD module 18. Therapeutic alliance is measured using the Session Rating Scale (SRS) at the start of each OSI-OCD module 19. Progress towards individually agreed goals is measured using Goal-Based Outcomes (GBOs) at the start of each OSI-OCD module 20. Overall clinical improvement is measured using the Clinical Global Impressions – Improvement scale (CGI-I) at 20 weeks post-randomisation and 32 weeks post-randomisation 21. Therapist treatment and supervision activity is measured using therapist treatment and supervision logs collected during OSI-OCD modules 0–9 and during treatment as usual 22. Treatment feasibility and acceptability are measured using qualitative interviews with parents, children, therapists, and stakeholders within four weeks after OSI-OCD treatment has finished 23. Feasibility parameters including willingness of therapists to recruit participants, number of eligible participants, follow-up rates, and questionnaire response rates are measured using trial records at end of study Ethics approval required East Midlands - Leicester Central Research Ethics Committee

2 Redman Place, Stratford

London United Kingdom E20 1JQ 25/EM/0159 10.1186/ISRCTN12117573 354658 CPMS: 69337, MR/Z503642/1 354658 69337 MR/Z503642/1 Interventional Randomized controlled trial Blinded (masking used) Placebo Parallel Treatment Not applicable Treatment 2027-06-30T00:00:00.000Z United Kingdom England Berkshire Healthcare NHS Foundation Trust

London House London Road

Bracknell England RG12 2UT RWX@2.16.840.1.113883.2.1.3.2.4.18.48 North East London NHS Foundation Trust

West Wing C E M E Centre Marsh Way

Rainham England RM13 8GQ RAT@2.16.840.1.113883.2.1.3.2.4.18.48 Mersey Care NHS Foundation Trust

V7 Building Kings Business Park Kings Drive

Prescot England L34 1PJ RW4@2.16.840.1.113883.2.1.3.2.4.18.48 Northamptonshire Healthcare NHS Foundation Trust

St Marys Hospital 77 London Road

Kettering England NN15 7PW RP1@2.16.840.1.113883.2.1.3.2.4.18.48 Herefordshire and Worcestershire Health and Care NHS Trust

Unit 2 Kings Court Charles Hastings Way

Worcester England WR5 1JR R1A@2.16.840.1.113883.2.1.3.2.4.18.48 Manchester University NHS Foundation Trust

Cobbett House Oxford Road

Manchester England M13 9WL R0A@2.16.840.1.113883.2.1.3.2.4.18.48 Patient false 1. Child has been diagnosed with OCD on the basis of the ADIS-C or ADIS-P by the research team. 2. Parent/carer is willing and able to give informed consent for participation in the study on behalf of their child and themselves. 3. Child is willing and able to give informed assent for participation in the study. 4. Child aged 5–12 years. 5. Child has been referred to services that provide psychological support for child mental health problems on behalf of the NHS. 6. Child and parent/carer are able to understand, read, and communicate in English. 7. Parent/carer is willing and able to engage with the online intervention platform (OSI) if randomised to the OSI for OCD treatment arm. 8. Parent/carer is willing and able to complete required assessments. Child 5 Years 12 Years All 48 0 1. The child is currently receiving any other psychological intervention. 2. The child is receiving psychotropic medication and the dose has not been stable for at least two months. 3. The child has a confirmed or likely diagnosis of autism (indicated by a score > 15 on the Social Communication Questionnaire-lifetime version). 4. If the child has profound learning difficulties evidenced by attending a specialist school. 5. If there are risk and/or safeguarding concerns which are paramount and would interfere with treatment delivery, including suicidal intention, recurrent or potentially life-limiting self-harm, or if the child has a child protection plan/is on the child protection register/the research team consider the child to be suffering, or likely to suffer, significant harm. 6. Parent/carer or child is unable to understand, read, or communicate in English, which would prevent meaningful participation in the intervention or assessments. 7. The child is referred to a clinical team where the only usual treatment option is the University of Oxford’s face-to-face/telephone version of brief therapist guided, parent-led CBT for OCD 2025-09-01T00:00:00.000Z 2026-10-31T00:00:00.000Z Specialty: Mental Health, Primary sub-specialty: Personality disorder - OCD; Health Category: Mental health; Disease/Condition: Neurotic, stress-related and somatoform disorders Mental and Behavioural Disorders Families taking part in the study will be randomly assigned to one of two groups: either the OSI for OCD intervention or treatment as usual (TAU) within mental health services that provide treatment on behalf of the NHS. Stratified randomisation will be conducted using a web-based randomisation tool designed for clinical trials and research studies to ensure balance across key variables, including: Child’s age (e.g., ≤8 years; >8 years), Gender and OCD symptom severity (measured by baseline CY-BOCS scores). We will use a randomisation tool that operates through a secure online platform, accessible only to authorised study personnel. Participants will be randomly assigned to either the OSI for OCD (n=24) or treatment as usual (TAU) arms (n=24), within one month of completing baseline assessments. Families allocated to the OSI for OCD treatment will be added to the online intervention platform by the research team, from which they can start their treatment, with therapist support. This includes completing 10 online modules, with 10 x 20-30 minute phone calls (including 8 therapist sessions, and 2 check-ins). For families in the OSI for OCD group, routine outcome measures (ROMs) that are collected as part of this treatment will also be available to the research team. OSI treatment lasts for approximately 4 months. Families assigned to TAU will receive their usual care, and information on the nature of this treatment will be collected from therapists and supervision logs. Parents and children will be invited to complete post-treatment and follow-up questionnaires and interviews online at 20 and 32 weeks after randomisation. To address researcher bias, outcome assessors, who will conduct the diagnostic and clinical assessments, will be blinded to the treatment allocation of participants. This is to ensure that data collection for primary and secondary outcomes remains unbiased. Note. The research team will call all families to let them know the outcomes of the ADIS-C/P and CY-BOCS at 20 weeks and 32 weeks post randomisation. All families who complete these interviews will be provided with a letter summarising the outcomes following their final interview. Trial therapists will be identified through the participating trial sites. An embedded process evaluation will explore how to optimise the design of a future definitive non-inferiority trial RCT and subsequent wider implementation of OSI for OCD, if indicated. A subset of parents (~15) and children (~15) from the OSI for OCD treatment arm will be invited to take part in qualitative interviews. This may include those who completed the OSI for OCD treatment, as well as those who did not fully complete it, so we can understand a range of perspectives. We will also invite up to 15 therapists, clinical supervisors, clinical leads, and commissioners from the OSI for OCD arm. These interviews will explore (a) the implementation and acceptability; (b) mechanisms of impact; and (c) contextual factors that affect delivery, engagement, and outcomes, for OSI for OCD. These interviews will involve up to 15 parents and 15 children from the OSI for OCD group, as well up to 15 therapists, clinical supervisors, clinical leads and commissioners. The adequacy of the sample size will be continually reviewed, and recruitment will end when the sample holds sufficient information power to provide a rich insight into the research questions. Interviews will be conducted by research team members online and will be recorded and transcribed for analysis. In addition to qualitative interviews, the process evaluation aims to collect data to assess the acceptability of the intervention and how the intervention was implemented, including therapist treatment logs, usage data from the OSI platform, and clinical outcome measures. This information will help determine whether OSI for OCD is a feasible and effective approach for supporting families of children with OCD. Other The datasets generated during and/or analysed during the current study will be stored in a publicly available repository. Once analyses are complete and the linking document containing personal details is deleted, a sufficiently anonymised version of the data will be made available in a public repository, such as the UK Data Service. The data collected about participants (i.e., parents, their children, therapists and other stakeholders) will be preserved and made available in a form in which they cannot be identified. To ensure this, all data will be pseudonymised before archiving, and any direct identifiers (e.g., names, contact details) will be removed or stored separately. Data shared for future research or collaboration will be checked for potential identifiers before being made accessible. Stored in publicly available repository 6057a191-c581-4163-8d9f-e4aae53960d8 c3b9b209-e161-4fac-8faa-2490cbf35bc3 472c2e60-6c03-47cd-8310-b38dad1ad75e Yes Chloe Chessell Scientific

Postdoctoral Researcher, University of Oxford. Life and Mind Building, South Parks Rd

Oxford United Kingdom OX1 3EL - chloe.chessell@psych.ox.ac.uk Public University of Oxford Hospital/treatment centre https://ror.org/052gg0110 Non-commercial Medical Research Council http://dx.doi.org/10.13039/501100000265 11309942 true Sleep apnoea symptoms and prevalence in people attending memory services SAM The primary objective of this study is to determine prevalence of sleep apnoea in UK memory services, with an exploratory aim to determine whether sleep apnoea prevalence differs between different types of dementia diagnosis. Secondary objectives are to: determine clinical factors/symptoms that best predict sleep apnoea in people who present to memory clinics, determine the feasibility of remote questionnaires for sleep apnoea screening, and pilot methodology for observing the effect of treating sleep apnoea on blood biomarkers for Alzheimer’s disease and neurodegeneration. Background and study aims This study wants to find out how many people who have memory and thinking problems also have sleep apnoea. It will also look at what symptoms are related to having sleep apnoea in people with memory and thinking problems. What is sleep apnoea? Sleep apnoea is when your breathing stops and starts while you sleep. Pauses in breathing are called “apnoeas” and can last from a few seconds up to a minute. Too many apnoeas might affect how deep and restful your sleep is. Many people do not know they have sleep apnoea. Who can participate? People attending memory clinics at a participating site. What does the study involve? First, patients will be asked to complete a consent form to say they are happy to take part. Some information will be taken from medical records, and participants will be asked to complete some questionnaires (online if possible, but on paper or by telephone otherwise) about themselves and their sleep. Participants will be asked to wear a device called a WatchPAT for one night whilst sleeping at home. The device looks like a watch but also has a finger sleeve and a sticky pad that attaches to the chest. The WatchPAT will check for sleep apnoea. Participants and their GP will be informed of the results (whether they have sleep apnoea) and what the next steps are. If referred for sleep apnoea treatment in the Bristol area, the study team may ask to take some blood samples before and after treatment to see if levels of certain proteins change after treatment for sleep apnoea. Taking part is optional. Patients can also decide to take part and change their minds later. This decision won’t have an impact on their healthcare. What are the possible benefits and risks of participating? Participants may get a new diagnosis of sleep apnoea. Treating sleep apnoea may improve sleep quality, reduce the risk of other health conditions such as strokes, and help people feel better in the daytime. If someone has severe sleep apnoea or feels very sleepy in the day, they may be asked to stop driving or take a driving test to make sure they and others around them are safe. This is an observational study which carries no significant risks. The main risks has already been listed (implications on insurance and driving). Where is the study run from? The memory clinic that the patient attends and from home. Several memory clinics across the country are taking part. The research is being led by North Bristol NHS Trust, UK. When is the study starting and how long is it expected to run for? The study is scheduled to start in late 2025 and recruit until August 2026 (or 10 months from opening). Most participants will only be involved in the study for a very short time, though participants referred for sleep apnoea treatment at the Bristol site may be involved for several months, with blood tests every 4-8 weeks. Who is funding the study? 1. The National Institute for Health and Care Research (NIHR), UK. 2. Goldman Foundation. Who is the main contact? Study coordinator Victoria Gabb, victoria.gabb@bristol.ac.uk The proportion of people in memory clinics who have at least mild sleep apnoea (Oxygen Desaturation Index 3% > 5) according to a single night of overnight polygraphy (WatchPAT) 1. The proportion of people with different aetiological diagnoses in memory clinics who have at least mild sleep apnoea (Oxygen Desaturation Index (ODI)3% > 5) according to a single night of overnight polygraphy (WatchPAT). 2. The proportion of people in memory clinics who have mild (ODI 3% > 5-15), moderate (ODI 3% > 15-30) or severe (ODI 3% > >30) sleep apnoea according to a single night of overnight polygraphy (WatchPAT). 3. Proportion of people in memory clinics who have at least mild sleep apnoea (Oxygen Desaturation Index 4% > 5) according to a single night of overnight polygraphy (WatchPAT). 4. Diagnostic accuracy of STOP-BANG, Epworth Sleepiness scale and extra questions for at least mild sleep apnoea 5. Data completeness for online (or telephone, face-to-face) questionnaires in this population. Ethics approval required North West - Greater Manchester South Research Ethics Committee

3rd Floor, Barlow House 4 Minshull Street

Manchester United Kingdom M1 3DZ 25/NW/0221 10.1186/ISRCTN11309942 340207 CPMS: 61703, NIHR: 207185 340207 61703 207185 Multi-centre observational cross-sectional study with a longitudinal observational cohort sub-study at one site Observational Cross sectional study Other 2026-12-31T00:00:00.000Z United Kingdom England North Bristol NHS Trust

Southmead Hospital Southmead Road Westbury-on-trym

Bristol England BS10 5NB RVJ@2.16.840.1.113883.2.1.3.2.4.18.48 Bradford District Care Trust

New Mill Victoria Road

Shipley England BD18 3LD Y04099@2.16.840.1.113883.2.1.3.2.4.18.48 Cornwall Partnership NHS Foundation Trust

Carew House Beacon Technology Park Dunmere Road

Bodmin England PL31 2QN RJ8@2.16.840.1.113883.2.1.3.2.4.18.48 North East London NHS Foundation Trust

West Wing C E M E Centre Marsh Way

Rainham England RM13 8GQ RAT@2.16.840.1.113883.2.1.3.2.4.18.48 Northumbria Healthcare NHS Foundation Trust

North Tyneside General Hospital Rake Lane

North Shields England NE29 8NH RTF@2.16.840.1.113883.2.1.3.2.4.18.48 Patient 1. Patient attending an NHS memory clinic at an included recruitment site 2. Adults aged 18 or over 3. Patients who are able to consent for themselves Bloods sub-study only 1. New diagnosis of sleep apnoea 2. Recruited at the Bristol recruitment site 3. Referred to the sleep clinic 4. Consented to optional bloods sub-study when joining the study Mixed 18 Years 99 Years All 453 0 1. Adults without capacity to consent to the research study. 2. Being unwilling to use the WatchPAT device. Bloods sub-study only 1. Being unwilling or unable to travel to the Bristol Brain Centre for blood tests, where blood tests at home are not feasible. 2025-11-28T00:00:00.000Z 2026-11-30T00:00:00.000Z Sleep apnoea in patients attending memory clinics Nervous System Diseases Main study Participants will be asked to complete questionnaires to identify risk factors and symptoms relating to sleep apnoea and undergo a night of sleep apnoea screening using the WatchPAT polygraphy device. Data will also be collected from medical records. Participants will be informed of their results. Bloods sub-study Participants with sleep apnoea who are referred to treatment at the North Bristol site will be invited to undergo blood tests before and after treatment to assess whether blood biomarkers change following treatment for sleep apnoea. The study will also pilot a methodology for determining the change in serum biomarkers of Alzheimer’s disease and neurodegeneration after starting sleep apnoea treatment and report the change over time in biomarkers. Not Specified Data sharing statement to be made available at a later date 2026 Protocol article in https://doi.org/10.3389/fnagi.2026.1862599 (added 14/08/2026) Protocol

ed63387c-8427-46fa-9ca9-98c53c4e2cad 494f40d9-4283-49c8-8399-2bac559278c8 0f8dfbf7-a251-4628-8486-f40dde5868d9 afd0d6e2-cadc-4f61-8618-8be0888702d3 4c81de5d-a772-42d3-91e3-cad67f79313a No Victoria Gabb https://orcid.org/0000-0002-7688-766X Public Scientific

Victoria Gabb ReMemBr Group Research Team Bristol Brain Centre Elgar House Southmead Hospital

Bristol United Kingdom BS10 5NB 0117 456 0700 victoria.gabb@bristol.ac.uk Public Elizabeth Coulthard https://orcid.org/0000-0002-0017-9595 Principal investigator

Dementia Research Team Bristol Brain Centre Elgar House Southmead Hospital

Bristol United Kingdom BS10 5NB 0117 414 7801 elizabeth.coulthard@bristol.ac.uk Public North Bristol NHS Trust Hospital/treatment centre https://ror.org/036x6gt55 Non-commercial National Institute for Health and Care Research http://dx.doi.org/10.13039/501100000272 Goldman Foundation 67429289 true A peer-delivered programme for mental health disclosure distress and internalised stigma (Let’s Talk) in comparison to treatment as usual in adults with psychosis: A randomised controlled trial to investigate the efficacy of a peer intervention targeted at stigma-related mechanisms Let's Talk 2 The study objective is to establish Let’s Talk’s clinical efficacy in a multisite Randomised Controlled Trial (RCT) for adults with psychosis who report moderate to severe Internalised Stigma (IS) and disclosure-related distress; and to assess whether improved measures of personal recovery are mediated via key stigma variables. The objective is to recruit 352 participants to detect a target difference of 4.5 points on the QPR. Eligible participants will be randomised to either the intervention arm (Let’s Talk + Treatment as Usual (TAU)) or the control arm (TAU alone). Participants allocated to the intervention will be offered up to 16 sessions over a four-month intervention window with up to one booster session. Outcome data will be collected at baseline, at 4-month assessment (end of treatment) and at 12-month assessment (12 months post-randomisation). The study will determine whether the treatment effect on recovery is mediated by key mechanisms targeted in the intervention: (1) reduced IS (primary mechanism), (2) reduced stigma stress (degree to which perceived stigma is exceeded by personal coping resources for stigma) and (3) reduced disclosure distress. Background and study aim People who experience psychosis often face stigma and discrimination, which can negatively affect how they consider themselves and their identities. This is referred to as ‘internalising’ stigma. This can cause serious problems with self-esteem, cause depression and anxiety, and lead to withdrawal from others, study or work. To help people with psychosis feel less troubled by ‘internalised stigma’, mental health researchers in Manchester adapted an American intervention into a new intervention called ‘Let’s Talk’. A small trial was conducted to test this intervention. Let’s Talk involved Peer Support Workers (PSWs), who also have experience of psychosis, meeting with people taking part in the trial (Peers). PSWs and Peers discussed mental health stigma, and how to talk about mental health difficulties with others. Many sessions focused on helping Peers understand how to decide whether they want to discuss their mental health difficulties with others, or not. The trial found that people were interested in taking part, that most participants offered the intervention attended the sessions, and most participants attended the research assessments. A larger trial of Let’s Talk is planned to understand more clearly how it can help improve the personal wellbeing of people who experience psychosis. In a larger trial, more participants can be included and more advanced research tests can be run to see what parts of the Let’s Talk approach are most helpful. This would help make Let’s Talk as effective as possible, and it could then be offered in NHS mental health services. Who can participate? People in four UK areas aged 16+ who meet an ICD-11 Schizophrenia or other primary psychotic disorders diagnosis (as determined by the participant’s clinical team) or are receiving care for psychosis from Early Intervention Services (EIS), or under the care of a secondary or tertiary mental health service at the point of referral to ensure provision of care. They will also report moderate to severe self-reported disclosure-related distress (scoring >3 on the disclosure distress screening item), and moderate to severe internalised stigma (scoring of ≥3 on at least one of the Internalised Stigma domains of the Semi-structured Interview Measure of Stigma (SIMS)). What does the study involve? Participants will meet with a research assistant (RA), and they will complete a range of questionnaires, including the Questionnaire about the Process of Recovery (QPR). Participants will be randomly allocated (50:50 chance) to either receive the peer-delivered Let’s Talk intervention (plus their usual mental health treatment) or receive their usual mental health care alone (TAU). Participants who are allocated to receive the Let’s Talk intervention will be offered sessions with a peer support worker over 16 weeks, which will involve completing an 8-module workbook together. Participants will meet with research assistants again at 4 and 12 months to complete the same set of questionnaires. What are the possible benefits and risks of participating? If the Let’s Talk intervention is found to improve personal recovery outcomes, this could add to the current evidence base for helpful psychological interventions and potentially benefit future mental health services for people experiencing psychosis. A potential risk is that participants may find the research assessment process distressing. Participants will be offered choices around their assessments, including the option of breaks and assessments spread across multiple occasions. Where is the study run from? The lead site is Greater Manchester Mental Health NHS Foundation Trust (GMMH). Avon and Wiltshire Mental Health Partnership NHS Trust (AWP), South London and Maudsley NHS Foundation Trust (SLaM) and North East London NHS Foundation Trust (NELFT) are also sites from which the Let’s Talk 2 study is run. When is the study starting and how long is it expected to run for? May 2025 to August 2028. The study will begin enrolling participants in November 2025 to May 2027. Overall, the study is expected to run for 40 months. Who is funding the study? National Institute for Health and Care Research (NIHR), UK. Who is the main contact? Dr Melissa Pyle, based at Greater Manchester Mental Health NHS Foundation Trust (GMMH), melissa.pyle@gmmh.nhs.uk Personal recovery will be measured using the total score on the 15-item Questionnaire about the Process of Recovery (QPR) at 4 months The following secondary outcome measures will assess relevant dimensions of psychiatric distress and quality of life at baseline, 4 and 12 months: 1. Social anxiety will be measured using the Social Interaction Anxiety Scale (SIAS) 2. Depression will be measured using the Patient Health Questionnaire-9 (PHQ-9) 3. Satisfaction in multiple life domains and in treatment aspects will be measured using the DIALOG 4. Paranoia will be measured using the revised Green et al. Paranoid Thoughts Scale (R-GPTS) 5. The presence and impact of non-auditory hallucinations will be assessed using The Psychotic Symptoms Rating Scale: Multimodal Hallucinations. This is an unpublished scale adapted from PSYRATS-AH. The proposed mechanisms of action for Let’s Talk will also be measured with the following instruments at baseline, 4 months and 12 months: 1. Experienced, perceived, and internalised stigma will be measured using the Semi-structured Interview Measure for Stigma in Psychosis (SIMS) 2. Stigma stress will be assessed by the 8-item Stigma Stress Scale (SSCI-8) 3. Disclosure distress will be measured using the single-item Distress Disclosure Index (DDI) Ethics approval required Cambridge South Research Ethics Committee

Equinox House, City Link

Nottingham United Kingdom NG2 4LA 25/EE/0718 10.1186/ISRCTN67429289 343302 CPMS: 62177, NIHR: 163493 343302 62177 163493 Randomized controlled trial Interventional Randomised controlled trial Treatment 2028-08-31T00:00:00.000Z United Kingdom Greater Manchester Mental Health NHS Foundation Trust

Prestwich Hospital Bury New Road Prestwich

Manchester England M25 3BL RXV@2.16.840.1.113883.2.1.3.2.4.18.48 Bethlem Royal Hospital

Monks Orchard Road

Beckenham England BR3 3BX Y7O8M@2.16.840.1.113883.2.1.3.2.4.18.48 North East London NHS Foundation Trust

West Wing C E M E Centre Marsh Way

Rainham England RM13 8GQ RAT@2.16.840.1.113883.2.1.3.2.4.18.48 Avon and Wiltshire Mental Health Partnership NHS Trust

Bath NHS House Newbridge Hill

Bath England BA1 3QE RVN@2.16.840.1.113883.2.1.3.2.4.18.48 Patient Current inclusion criteria as of 03/07/2026: 1. Age 16+ years 2. Meet the ICD-11 schizophrenia or other primary psychotic disorders diagnosis (as determined by the participant’s clinical team) or be receiving care for psychosis from Early Intervention Services (EIS) to account for diagnostic uncertainty in the early stages of psychosis or be attending NHS mental health services for the treatment of psychosis. 3. Under the care of a secondary or tertiary mental health service at point of referral to ensure provision of care. 4. Able to provide written, informed consent (for ethical considerations). 5. Willing to engage in a peer support intervention. 6. Moderate to severe self-reported disclosure-related distress as determined by scoring >3 on the disclosure distress screening item. 7. Moderate to severe internalised stigma as determined by a score of >=3 on at least one of the Internalised Stigma domains of the Semi-structured Interview Measure of Stigma. Previous inclusion criteria: 1. Age 16+ years 2. Meet the ICD-11 schizophrenia or other primary psychotic disorders diagnosis (as determined by the participant’s clinical team) or be receiving care for psychosis from Early Intervention Services (EIS) to account for diagnostic uncertainty in the early stages of psychosis. 3. Under the care of a secondary or tertiary mental health service at point of referral to ensure provision of care. 4. Able to provide written, informed consent (for ethical considerations). 5. Willing to engage in a peer support intervention. 6. Moderate to severe self-reported disclosure-related distress as determined by scoring >3 on the disclosure distress screening item. 7. Moderate to severe internalised stigma as determined by a score of >=3 on at least one of the Internalised Stigma domains of the Semi-structured Interview Measure of Stigma. Mixed 16 Years 100 Years All 352 0 1. A primary diagnosis of alcohol or substance dependency, where this is clearly the cause of their psychotic symptoms. This does not exclude people who use substances or alcohol, only those with a primary diagnosis. This will be confirmed by participants' care teams. 2. A diagnosis of moderate to severe learning disability. This will be confirmed by participants' care teams. 3. An ICD-11 diagnosis of organic psychosis. This will be confirmed by participants' care teams. 4. Language barriers that are an obstacle to participation, since we are unable to provide translation of the intervention workbook or interpreters during intervention sessions. 5. Immediate risk to self or others. This will be confirmed by participants' care teams. 6. Currently receiving structured, individual psychological therapy. 2025-11-01T00:00:00.000Z 2027-05-31T00:00:00.000Z Schizophrenia, schizotypal and delusional disorders, psychosis Mental and Behavioural Disorders Design A clinical efficacy randomised controlled trial (RCT) will be conducted across 4 NHS secondary or tertiary care mental health services in the UK: Avon and Wiltshire, Greater Manchester, North East London, and South London. Participants who meet all inclusion criteria and no exclusion criteria will be randomly allocated to either Let’s Talk plus treatment as usual (TAU), or TAU alone. Participants will be randomised at the individual level via a Clinical Trials Unit (CTU)-hosted, web-based system using random permuted blocks. Randomisation will be at a 1:1 ratio, stratified by site. Outcome and mediational variables will be collected in research assessments at baseline, 4 months (end of treatment) and 12 months post-randomisation. The assessments will be conducted by raters who are blind to participant allocation. Clinical efficacy aims 1. To establish the efficacy of Let’s Talk + TAU in improving personal recovery (primary outcome) when delivered to adults with psychosis who report moderate to severe internalised stigma and disclosure-related distress compared to TAU alone. 2. To establish the efficacy of Let’s Talk + TAU on secondary outcomes of improving quality of life, reducing depression, and reducing social interaction anxiety compared to TAU alone. Clinical efficacy hypotheses 1. Let’s Talk plus TAU will result in improved measures of personal recovery at the end of treatment (4-month follow-up; primary outcome) and 12-month follow-up compared to TAU alone. 2. Let’s Talk plus TAU will result in improved quality of life at the end of treatment (4-month follow-up) and 12-month follow-up compared to TAU alone. 3. Let’s Talk plus TAU will result in a reduction in the level of depression and social interaction anxiety at the end of treatment (4-month follow-up) and 12-month follow-up. Mechanistic aims 1. To examine the extent to which Let’s Talk plus TAU impacts on measures of personal recovery via a decrease in stigma-specific processes (Internalised stigma [IS], stigma stress, and disclosure distress). Mechanistic hypotheses 1. Let’s Talk + TAU will lead to reductions in IS and stigma stress 2. The mechanisms by which Let’s Talk + TAU lead to improvements in personal recovery are due to reductions in IS, stigma stress and disclosure distress. Primary outcome The primary outcome will be the total score on the 15-item Questionnaire about the Process of Recovery (QPR) at 4-month follow-up. The QPR was developed in collaboration with patients to assess personal recovery from psychosis, containing items that were initially derived from qualitative interviews about this topic. It has excellent reliability, validity, and sensitivity to change and is nationally adopted as a PROM for evaluation of early intervention for psychosis services, forming part of the Mental Health Services Data Set. Patients consistently prioritise personal recovery over specific symptom change, and the QPR has been cited as the only measure of recovery that directly maps onto all 5 processes of the influential CHIME framework of personal recovery. Secondary outcomes Secondary outcomes will assess relevant dimensions of psychiatric distress and quality of life. 1. The Social Interaction Anxiety Scale (SIAS), a 20-item self-administered scale questionnaire, which reflects anxieties people may encounter in social situations. Items are rated on a 5-point scale from 0 (not at all) to 4 (extremely). The SIAS is a reliable and valid measure, with initial testing demonstrating high levels of internal consistency and test-retest reliability. 2. Depression will be measured using the Patient Health Questionnaire-9 (PHQ-9), a validated, nine-item, patient-reported outcome measure (PROM). The PHQ-9 is a brief self-administered scale which reflects the DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, fifth edition) criteria. It classifies current symptoms on a scale of 0 (not at all) to 3 (nearly every day). 3. The DIALOG scale is a validated, 11-item, patient-reported outcome and experience measure (PROM/PREM). The DIALOG scale assesses eight life domains (mental health, physical health, job situation, accommodation, leisure, partner/family, friendship, personal safety) and three treatment aspects (medication, practical help, meetings with healthcare professionals). The items are rated on a 7-point scale from “totally dissatisfied” to “totally satisfied” with the value 4 representing a neutral “in the middle.” 4. The Psychotic Symptoms Rating Scale: Multimodal Hallucinations, an unpublished scale adapted from the PSYRATS: Auditory Hallucinations subscale for assessing the presence and impact of nonauditory hallucinations. 5. The Revised Green et al Paranoid Thoughts Scale (R-GPTS), a reliable measure of paranoia comprising two subscales to assess ideas of reference (Part A; 8 items) and ideas of persecution (Part B; 10 items), over the past month. The two subscales are designed to be treated as distinct measures and should be scored separately. A total score for each subscale is obtained by adding together the items. Items are scored on a 4-point scale from 0 (Not at all) to 4 (Totally). Mechanistic outcomes The proposed mechanisms of action for Let’s Talk will also be measured with the following instruments: 1. The Semi-structured Interview Measure for Stigma in Psychosis (SIMS), which assesses experienced, perceived, and internalised stigma. 2. Stigma stress will be assessed by the 8-item Stigma Stress Scale. 3. Disclosure-related distress will be assessed using a single item from the Disclosure Distress Scale. Assessment schedule Research assessments comprising the above measures will be completed at baseline, 4 months (end of treatment) and 12 months post-randomisation. Participants will receive £25 on completion of each research assessment as a token of appreciation for their time (£75 total). Treatment condition (Let's Talk + TAU) Let’s Talk will be delivered, in addition to TAU, on a one-to-one basis by Peer Support Workers (PSWs). A 4-month treatment window permits ≤16 sessions, with an option for 1 booster session to consolidate gains. The expectation for delivery is in-person, but the intervention can be delivered remotely via video call or telephone as a contingency. The aims of Let’s Talk are to: help participants weigh pros and cons of disclosing which vary by setting (e.g., disclosure at one’s employment has different costs and benefits than disclosure to one’s friendship network); teach relatively safe ways to disclose should the person decide to do so; help people craft stories that reflect their disclosure goals; support participants with internalised stigma and developing affirming self-beliefs. Sessions with the PSW will be structured around the Let's Talk manual and workbook, which have been refined based on qualitative feedback from participants and PSWs in the Let's Talk feasibility RCT. All participants allocated to Let’s Talk will receive a copy of the workbook. All routine or additional treatments in the comparator arm will be monitored. Comparator condition (TAU) The control condition is treatment as usual (TAU). All participants in the intervention and comparator arms are required to be under the care of a secondary or tertiary care mental health service as a condition of inclusion. In the UK, TAU for psychosis is based on the Care Programme Approach and typically includes psychiatric medication, assignment of community-based health and social care staff, care coordination, access to rehabilitative services, and outpatient care. Referrers for participants in the TAU arm will not be requested to withhold any treatment throughout the duration of the trial, and all routine or additional treatments will be monitored. Except for emergent risk issues, TAU alone will also not involve liaison between researchers and the participants’ healthcare teams. Research Assistants will identify any risks to self or others that require immediate action. All routine or additional treatments in the TAU arm will be monitored. Behavioural Data sharing statement to be made available at a later date Protocol

Migrated from study website field

86951dcc-2709-4977-93e7-386473d73385 ebf9cd3f-3712-4e66-8c43-5ffed88e1e87 930f7421-94a2-4fe9-bdd7-45895906a077 No Protocol file 48087_Protocol_V2.0_22Sept2025.pdf 6932fd62-0051-4487-9381-c93a98b39eef true application/pdf 745143 60d880bd51153d9dc2c4f27ea9cfce79 Participant information sheet 48087_PIS_V3_08Sept2025.pdf acb1f0de-12fc-4088-b5a4-262f760134b6 true application/pdf 304066 a6e5157f9f588469b3032ea140d1693a Protocol file ISRCTN67429289_Protocol_V4.0_19Mar2026.pdf 570ab5e4-3cc8-407d-bdd9-5c8af6e866b8 true application/pdf 831250 f1e9b8abf702a68f1689f7939553a448 Participant information sheet ISRCTN67429289_PIS_V4_19Mar2026.pdf 7d16f22b-6bcd-4d6f-936e-359058349b65 true application/pdf 304194 913611ee2cdba3fdb31190cc5bfb3c91 Melissa Pyle https://orcid.org/0009-0004-5337-9031 Public Scientific Principal investigator

Greater Manchester Mental Health NHS Foundation Trust The Psychosis Research Unit, R&I Central Park Hub, Building B Northampton Road

Manchester United Kingdom M40 5BP +44 (0)161 271 0084 melissa.pyle@gmmh.nhs.uk Public Greater Manchester Mental Health NHS Foundation Trust Hospital/treatment centre https://ror.org/05sb89p83 Non-commercial National Institute for Health and Care Research http://dx.doi.org/10.13039/501100000272 17977792 true Open Dialogue compared to usual care for adults experiencing a mental health crisis: a feasibility study for the ODDESSI trial ODDESSI 1. To assess whether it is possible and acceptable to conduct a full-scale cluster randomised trial comparing Open Dialogue (OD) to Treatment as Usual (TaU) across multiple locations. We will measure recruitment, consent, and retention rates at 3 months. 2. To assess the acceptability of primary and secondary outcome measures that will be used in the full scale trial, and to refine measures of cost-effectiveness of OD. 3. To set up the randomisation system in preparation for the main trial and to define and randomise clusters in two catchment areas. Background and study aims This trial forms part of a NIHR programme grant investigating the development and evaluation of Open Dialogue (OD) for severe mental illness. OD is being developed and adapted for delivery in five NHS trusts and is a service delivery model for individuals in mental health crisis, developed in Finland, which has a collaborative approach and explicitly targets social networks. Appropriate pharmaceutical, psychological or social interventions are involved in shared decision making with social networks and healthcare professionals. This is in contrast to current models of care, in which families are rarely directly involved. Studies to date are promising and report reductions in hospital bed usage and improved recovery rates, but there is currently no high-quality evidence to support a NHS-wide adoption of this model. This approach offers the possibility of a potentially effective alternative to the current model This trial aims to assess the feasibility of conducting a full multicentre cluster randomised controlled trial of the OD model compared to usual NHS crisis and longer-term community care (treatment as usual [TaU]) over 9 months. Participants will be eligible for the study if they are a service user in crisis with a primary diagnosis of a mental health disorder. The feasibility study will involve 2 OD teams and 2 TaU teams in two sites (NHS trusts). If the feasibility trial is successful, a multicentre cluster randomised controlled trial (RCT) with 28 clusters will be conducted over 3 years. This is a type of study where groups of participants (rather than individuals) are randomly assigned to different treatments, and the research is carried out at multiple locations or centres to improve the generalisability of the results. Who can participate? A service user in crisis within 24-48 hours of referral or having been discharged from in-patient care following a crisis admission to the Crisis Resolution and Home Treatment Team (CRHTT) for home treatment. The service user must be over the age of 18, have a diagnosis of a mental health disorder, and be able to give informed consent (or consent is provided by a personal or nominated consultee). What does the study involve? All eligible service users will first be contacted by a member of the clinical team to obtain their agreement to be approached by a member of the research team. The screening process and recruitment process will be supported by the relevant clinical team in order to support decisions of capacity and risk. The researcher will then contact the potential participant to explain the research study and send an information sheet to them via post or email. Potential participants will be given time (48 hours) to consider the information before the researcher contacts them again to answer any questions. Service users will already be receiving OD or Treatment as Usual (TaU) as part of their care, and their treatment will continue regardless of their participation in the study. Appropriate psychological and pharmacological treatments will be deployed in either treatment as necessary. The participants randomised to the OD clusters will receive the OD intervention. The OD intervention focuses on the social network to improve outcomes for service users. Typically, in the first few network meetings, two OD staff members as well as the social network are present. The service user and their network decide the length and frequency of meetings as well as the focus of discussions. The OD staff members are present to facilitate the meetings amongst the social network. TaU will be routine crisis care and follow-up community care, which typically involves care from a CRHTT with an average duration of contact from 2-6 weeks, and, where appropriate, ongoing care from community services including psychological interventions. Baseline interviews will be conducted over the phone or in patients' homes. Follow-up assessments will occur in the three months post-recruitment. The researcher will contact the participant to arrange a convenient time and date to meet. Participants will complete a set of outcome measures. What are the possible benefits and risks of participating? The benefits for participants are that they will be involved in the development of a potentially effective alternative to the current model of care for mental health crises. Service users randomised to the OD intervention will benefit from the coordinated and continuous care that the OD model offers. Service users randomised to the TaU intervention will benefit from a clear referral pathway to crisis services. No major risks are anticipated for participants. The research interviews may, in some cases, involve discussing sensitive topics. There is the potential for participants to get upset. Although we anticipate this is unlikely, a member of the ODDESSI study team will be present during the interview if the service user does become distressed. A senior member of the research team will be able to support them and direct them to further support services. Where is the study run from? The study will run across two UK NHS sites, North East London NHS Foundation Trust and Kent and Medway NHS and Social Care Partnership Trust. When is the study starting and how long is it expected to run for? June 2018 to June 2019 Who is funding the study? National Institute for Health and Care Research (NIHR), UK Who is the main contact? Dr Sandeep Toot, sandeep.toot@nelft.nhs.uk To assess the feasibility and acceptability of conducting a randomised controlled trial of the OD intervention versus TaU, the study will collect the following data: 1. Recruitment to the trial, measured by observing the number of participants after recruitment 2. Consent rate, measured using the number of participants providing full consent after screening 3. Retention rates, measured using the number of participants who remained in the study at the end of the study period Acceptability will be assessed through the successful completion of the following participant-level secondary outcome measures: The following measures are recorded at baseline: 1. Socio-demographics measured using data collected on a form created specifically for the trial, which records: date of birth, gender, ethnicity, country of birth, education, employment, marital status, and housing 2. Symptom severity measured using the Brief Psychiatric Rating Scale (BPRS) 3. Social network quality measured using the Social Provisions Scale (SPS), and social network size measured using the Lubben Social Network Scale - 6 item (LSNS-6) 4. Burden of care on caregivers measured using the Burden Assessment Scale (BAS) 5. Health-related quality of life measured using the EQ-5D-5L 6. Hospitalisation rate, defined as an inpatient admission post-index admission, and re-referral to Crisis Resolution and Home Treatment Teams (CRHTT), measured using data collected from anonymised patient electronic medical records The following outcome measures are recorded at 3-month follow-up: 8. Time to first relapse in days following recovery (primary outcome measure in the main trial), measured using anonymised case notes by the chief investigator, a psychiatrist and a senior clinician (to define point of recovery) 9. Service user and carer satisfaction with care, measured by the Client Satisfaction Questionnaire (CSQ-8) 10. Use of health, social care services and wider societal costs measured using an adapted version of the self-report Client Services Receipt Inventory (CSRI) 11. Service user and primary clinician experience of shared decision making during treatment, measured by patient and clinician self-report on the dyadic OPTION scale 12. Service user-defined recovery, measured by the Questionnaire about the Process of Recovery (QPR) Ethics approval required London-Bromley Research Ethics Committee

Level 3, Block B, Whitefriars, Lewins Mead

Bristol United Kingdom BS1 2NT 18/LO/0868 10.1186/ISRCTN17977792 233243 CPMS: 36235 233243 36235 Feasibility clustered randomized controlled trial Interventional Cluster randomised trial Treatment 2019-06-01T00:00:00.000Z United Kingdom England North East London NHS Foundation Trust

West Wing, CEME Centre, Marsh Way

Rainham England RM13 8GQ Kent and Medway NHS and Social Care Partnership Trust

Farm Villa Hermitage Lane

Maidstone England ME16 9PH RXY@2.16.840.1.113883.2.1.3.2.4.18.48 Service user Clusters must: 1. Be in a catchment area with a clear referral pathway to the community mental health service 2. Have protocols in place to deliver either OD or TAU 3. Contain a set of 2 to 4 geographically coterminous GP practices where 3.1. The cluster has an average number of referrals per cluster between 65 and 75 patients per year to crisis services 3.2. Each practice has a list size of over 2000 registered persons 3.3. Each practice refers only within the catchment area of the community MH service 3.4. Each practice only serves residents within the cluster catchment area (i.e. does not include practices which, as one of its primary functions, have the provisions of a student health service) Service users from a cluster are eligible to take part in the study if they are: 1. Meeting criteria of a service user in crisis (meeting ICD criteria (WHO, 1992) for a mental health disorder) within 24-48 hours of referral or having been discharged from in-patient care following a crisis admission to the Crisis Resolution and Home Treatment Team (CRHTT) for home treatment. There will be some variability in the operational definition of ‘crisis’ across Trusts and, therefore, participants presenting to services. However, this variation will increase the generalisability of trial findings. 2. 18 years and above 3. Able to provide informed consent, or have consent provided by a personal or nominated consultee Mixed 18 Years 99 Years All 60 59 1. Having a diagnosis of dementia or a learning disability 2. Having a primary diagnosis of substance misuse 3. Having an acquired cognitive impairment 4. Being unable to comprehend both written and verbal English 5. Being under the care of forensic services 6. Being considered too high risk through participation in the study; that is, participation in the study is judged by the service users’ clinician to pose potential harm to themselves or the research/clinical team 7. Residing outside their GP catchment area 8. Having no fixed abode 9. Currently participating in another research trial, which could affect their participation in this trial 2018-07-30T00:00:00.000Z 2019-02-18T00:00:00.000Z Severe mental illness Mental and Behavioural Disorders Overview The research team will undertake a feasibility trial to assess whether it is possible to conduct a full-scale trial comparing Open Dialogue (OD) to Treatment as Usual (TaU). They will undertake a cluster randomised controlled trial, comprising four clusters of two Open Dialogue (OD) teams and two Treatment as Usual (TaU) teams in two NHS sites. Each of the pilot sites will be staffed by a team of therapists trained in OD, and all staff have agreed at least in principle to participate in a rigorous RCT. Please note that these service users will already be receiving OD or TaU as part of their care, and their treatment will continue regardless of their participation in the study. This is approximately 10% of the total sample size to be recruited. Randomisation The study will take place in four clusters from two catchment areas. For this feasibility trial, two separate catchment areas, whose clusters have already been established and randomised in preparation for the future RCT, will each provide two clusters (one allocated OD, and another allocated to TaU) to the current study. Randomisation will be carried out by statisticians with support from King's Clinical Trials Unit (KCTU). Recruitment & Screening The aim is to recruit 15 service users from each of four teams (two OD teams and two TaU teams). The study team has drawn upon their shared clinical and research experience to create a clear recruitment protocol for researchers to utilise during recruitment. Referrals to either the OD or Tau participating teams will be screened by a member of the clinical team or clinical studies officer for eligibility against the inclusion and exclusion criteria. All eligible service users will first be contacted by a member of the clinical team to obtain their agreement to be approached by a member of the research team. The screening and recruitment processes will be supported by the relevant clinical team to inform decisions regarding capacity and risk. The researcher will then contact the potential participant to explain the research study and send an information sheet to them via post or email. Potential participants will be given time (48 hours) to consider the information before the researcher contacts them again to answer any questions. Consent and baseline If the service user is interested in taking part in the study, the researcher will agree on a time and date to obtain informed consent between two days and two weeks of presentation to services. Participants will be recruited over 6 months by a member of the research team, and followed up for 3 months post-presentation to services. Baseline measures will be recorded in an interview after the researcher has obtained informed consent. For those who lack the capacity to consent, a personal consultee who has no professional interests or incentives in the research or treatment will be identified. If a personal consultee cannot be identified, a nominated consultee will be identified and approached from the panel of consultees. Intervention Please note that these service users will already be receiving OD or Tau as part of their care, and their treatment will continue regardless of their participation in the study. Appropriate psychological and pharmacological treatments will be deployed in either treatment as necessary. OD The participants randomised to the OD clusters will receive the OD intervention. The OD intervention focuses on the social network to improve outcomes for service users. Typically, in the first few network meetings, two OD staff members as well as the social network are present. The service user and their network decide the length and frequency of meetings as well as the focus of discussions. The OD staff members are present to facilitate the meetings amongst the social network. TaU TaU will be routine crisis care and follow-up community care, which typically involves care from a (CRHTT) with an average duration of contact from 2-6 weeks, and, where appropriate, ongoing care from community services including psychological interventions. Follow-ups Follow-up assessments will occur in the three months post-recruitment. The researcher will contact the participant to arrange a convenient time and date to meet. The participant will complete a set of outcome measures. Measures The following measures will be delivered by researchers to assess their acceptability by participants. These outcome measures will be delivered by researchers. Each will be delivered at either baseline or follow-up and will be delivered only once to reduce time burden. The measures given at baseline include; -BPRS (Brief Psychiatric Rating Scale) -BAS (Burden of care on caregivers) -EQ-5D-5L (health-rated quality of life) -LSN (Lubben Social Network) -SPA (Social Provisions Scale) -demographics form The measures given at follow-up include: -QPR (Questionnaire about the Process of Recovery) -CSQ-8 (Service user and carer satisfaction with care) -CSRI (Client Service Receipt Inventory) -the dyadic OPTION scale (experience of shared decision making) The following outcome measures will be obtained from anonymised patient electronic medical records. -Time to first relapse in days following recovery -Hospitalisation rate defined as an inpatient admission post index admission, and re-referral to CRHTTs, will be obtained from anonymised patient electronic medical records. Analysis Recruitment, retention, and consent rates will be measured and assessed against the predetermined stop-go criteria to inform progression to the multicentre cluster RCT in work package 3 of the programme: -60 participants recruited (10% of the sample size to be recruited to the full trial) -retention of 80% of participants at 3-month follow-up -primary outcome data collected from 85% of participants at 3-month follow-up -expected consent rate of 66% -demonstration that all sites can establish clusters and that all OD teams operate within the agreed protocol (including referral pathways, caseload capacity and team composition) -demonstration that all OD teams across all sites achieve adequate adherence and fidelity Behavioural The researchers will be following the actions outlined by NIHR in regard to sharing research data. The datasets generated and analysed, and the corresponding statistical code, will be available in anonymised form from the research team on reasonable request, subject to review, following the publication of trial results. Dr Sandeep Toot, sandeep.toot@nelft.nhs.uk Available on request

0ebf0fca-88cd-44a0-ae44-7e6c4a599f81 396e3f17-bf4f-43d4-99cb-9a2e23d06f63 065d017d-cfc5-448a-a773-c74959d28a3b Yes Participant information sheet 48000_PIS_Carer_v1.3_28June2018.pdf 38ccde46-f7e5-40cf-b222-023156d321f6 true application/pdf 133173 3bef5ca5541de76ae434a1936ded81ab Participant information sheet 48000_PIS_Consultee_v1.3_28June2018.pdf 3e1634df-72bc-4ab8-9ebd-b7cb256a6968 true application/pdf 136829 908dc248d29b6dc0af85736d5c04c50c Participant information sheet 48000_PIS_v1.3_28June2018.pdf 3bfc316b-821c-4c80-9030-8d95abe745fd true application/pdf 133160 b86b6525fce9d17d5c32cda9abbd36b3 Stephen Pilling https://orcid.org/0000-0002-7361-8202 Public Scientific Principal investigator

The Department of Clinical, Educational and Health Psychology (CEHP), University College London, 1-19 Torrington Place

London United Kingdom WC1E 7HB +44 (0)20 7679185 s.pilling@ucl.ac.uk Public North East London NHS Foundation Trust Hospital/treatment centre https://ror.org/023e5m798 Non-commercial National Institute for Health and Care Research http://dx.doi.org/10.13039/501100000272 29596999 true A peer-led group programme for people with severe mental illness to reduce risk of cardiovascular disease (PEGASUS): A feasibility evaluation study PEGASUS feasibility study The aim of this research is to feasibility test a trained peer-supported group clinic intervention for people with SMI who have increased risk of CVD. Building on development work, evidence from a systematic review and an experience-based co-design process leading to the development of a co-produced peer-supported group clinic intervention, the objectives of this study are: 1. To establish the feasibility of the intervention for future evaluation in a randomised controlled trial (RCT), specifically: 1.1. Establish the feasibility of recruitment and retention strategies for the main trial 1.2. Assess the acceptability of, and retention to the planned intervention for individuals with SMI and elevated CVD risk 1.3. Determine the feasibility of collecting primary and secondary outcome data for the main trial 2. Estimate the location (proportion) and variability (confidence intervals) of the primary outcome to refine the power calculations for the main trial 3. To refine the content and delivery strategies for the intervention 4. To determine the best method of evaluating intervention implementation and fidelity Background and study aims People living with severe mental illness (SMI), such as schizophrenia or bipolar disorder, often have poorer physical health and can die 15–20 years earlier than the general population. One of the main causes of early death is heart disease. This risk is even higher for people from Black, Asian and minority ethnic communities. The PEGASUS study is testing a new group programme designed to help people with SMI reduce their risk of heart disease. The programme includes support with healthy eating, physical activity, and managing health goals, and is co-led by peer support workers (people with lived experience of mental health difficulties) and healthcare professionals. Who can participate? Adults who have a diagnosis of severe mental illness and also an elevated risk of cardiovascular disease may be able to take part. What does the study involve? Participants will be invited to join a group of 8–12 people for 10 sessions over 6 months. Each session lasts 2 hours and is led by a peer support worker and a healthcare professional. The sessions focus on different aspects of health and wellbeing. Participants will also have an individual ‘onboarding’ session before the group starts, four one-to-one sessions with a peer worker during the programme, and a reunion session after the programme ends. The study will also involve completing questionnaires and health checks at the beginning, middle, and end of the programme. Some participants may be invited to take part in an interview or focus group to share their views on the programme. What are the possible benefits and risks of participating? Taking part may help participants improve their physical health, feel more confident about managing their health, and feel more socially connected. There are no major risks, but some people may find it difficult to talk about their health or take part in group sessions. Support will be available throughout. Where is the study run from? City St George’s, University of London (UK) When is the study starting and how long is it expected to run for? August 2025 to September 2026 Who is funding the study? National Institute for Health and Care Research (NIHR) (UK) Who is the main contact? Dr Bethan Hatherall, bethan.hatherall@citystgeorges.ac.uk Jessica Catchpole, jessica.catchpole@citystgeorges.ac.uk Acceptability of intervention and study delivery as assessed by focus group/interviews at 3 and 6-months. 1. Participant recruitment and retention rate is measured using study records at baseline, 3 months, and 6 months 2. Waist circumference is measured using tape measurement at baseline, 3 months, and 6 months 3. Hip circumference is measured using tape measurement at baseline, 3 months, and 6 months 4. Body mass index (BMI) is measured using height and weight measurements at baseline, 3 months, and 6 months 5. Triglycerides are measured using fasting blood sample at baseline, 3 months, and 6 months 6. HDL-cholesterol is measured using fasting blood sample at baseline, 3 months, and 6 months 7. LDL-cholesterol is measured using fasting blood sample at baseline, 3 months, and 6 months 8. Total cholesterol is measured using fasting blood sample at baseline, 3 months, and 6 months 9. HbA1c is measured using blood sample at baseline, 3 months, and 6 months 10. Blood pressure is measured using automated sphygmomanometer at baseline, 3 months, and 6 months 11. Psychiatric symptoms are measured using the Modified Colorado Symptom Index at baseline, 3 months, and 6 months 12. Dietary behaviour is measured using the Dietary Instrument for Nutrition Education (DINE) adapted by IMPaCT at baseline, 3 months, and 6 months 13. Physical activity is measured using the International Physical Activity Questionnaire - Short Form (IPAQ-SF) at baseline, 3 months, and 6 months 14. Tobacco, cigarette, and betel nut or paan use is measured using self-report questionnaire at baseline, 3 months, and 6 months 15. Alcohol consumption is measured using the Alcohol Use Disorders Identification Test - Consumption (AUDIT-C) at baseline, 3 months, and 6 months 16. Health-related quality of life is measured using the EQ-5D-5L at baseline, 3 months, and 6 months 17. Depression is measured using the Patient Health Questionnaire-9 (PHQ-9) at baseline, 3 months, and 6 months 18. Self-efficacy is measured using the Generalised Self-Efficacy Scale at baseline, 3 months, and 6 months 19. Social network is measured using the Lubben Social Network Scale at baseline, 3 months, and 6 months 20. Therapeutic relationship is measured using the Scale to Assess the Therapeutic Relationship (STAR) at baseline, 3 months, and 6 months 21. Progress towards achievement of personalised lifestyle goals is measured using the Goal-Based Outcome Tool at baseline, 3 months, and 6 months 22. Health and social care service use is measured using the DIAMONDS Service Use Survey at baseline, 3 months, and 6 months 23. Physical activity levels are measured using one-week accelerometer wear at baseline, 3 months, and 6 months Ethics approval required Wales Research Ethics Committee 7

2 Redman Place, Stratford

London United Kingdom E20 1JQ 24/WA/0289 10.1186/ISRCTN29596999 326517 CPMS: 59641, NIHR: 204418 326517 59641 204418 Interventional non-randomized Interventional Non randomised study Treatment 2026-09-01T00:00:00.000Z United Kingdom England East London NHS Foundation Trust

Robert Dolan House 9 Alie Street

London England E1 8DE RWK@2.16.840.1.113883.2.1.3.2.4.18.48 North East London NHS Foundation Trust

West Wing C E M E Centre Marsh Way

Rainham England RM13 8GQ RAT@2.16.840.1.113883.2.1.3.2.4.18.48 Birmingham and Solihull Mental Health NHS Foundation Trust

Unit 1 50 Summer Hill Road

Birmingham England B1 3RB South West London and St George's Mental Health NHS Trust

Springfield Hospital 61 Glenburnie Road

London England SW17 7DJ Patient Current key inclusion criteria as of 18/12/2025: Service users participants will: 1. Be aged 18 to 75 years 2. Have capacity to consent to participate in research 3. Currently on the caseload of mental health services in community settings or on GP/ ICS severe mental illness (SMI) list 4. Current primary diagnosis of schizophrenia-spectrum disorders (ICD-10 diagnoses F20–29) or bipolar disorder (F31) or in Early Intervention for Psychosis Services (EIPS) with formal diagnosis of psychosis (ICD-10 diagnoses of F29) or an aforementioned diagnosis. 5. If on psychotropic medication, on stable dose for 90 days (N.B. This refers specifically to either adding or changing to a new antipsychotic medication, but not applies to dosage adjustment of a pre-existing antipsychotic medication.) 6. Enhanced CVD risk as indicated by any one of: i) Obesity defined as: waist circumference over 102cm in men (or >90cm in non-white men) or over 88cm in women (or >80cm in non-white women) or BMI≥25 kg/m2 (or ≥23 kg/m2 in non-white people) ii) Hypertension defined as: blood pressure over 130/85 mmHg or documented hypertension on medication iii) Dyslipidaemia defined as: fasting triglyceride level over 1.7mmol/l or total cholesterol ≥5.0 mmol/L or on medication for hyperlipidaemia (e.g. statin) or high-density lipoprotein (HDL) cholesterol level less than 0.9mmol/l (men)/1mmol/l (women) iv) Hyperglycaemia defined as: HbA1c > 37 mmol/mol (5.5%) or fasting plasma glucose level ≥5.6 mmol/l or documented Type-2 diabetes (T2D) 7. If on treatment for T2D, hypertension or hyperlipidaemia, on stable dose medication for at least 90 days Intervention staff: 1. Peer (support) workers and registered mental health nurses (or other healthcare professionals or practitioners with appropriate training) 2. Based at one of the participating sites/Trusts 3. Have been trained and engaged with the PEGASUS programme to deliver (co-facilitate) the PEGASUS intervention for the purposes of this study _____ Previous key inclusion criteria: Service users participants will: 1. Be aged 18 to 75 years 2. Have capacity to consent to participate in research 3. Service Involvement: 3.1 Currently on the caseload of mental health services in community settings 3.2 Or on GP/ICS severe mental illness (SMI) list 4. Diagnosis: 4.1 Current primary diagnosis of schizophrenia-spectrum disorders (ICD-10 diagnoses F20–29) 4.2 Or bipolar disorder (F31) 4.3 Or in Early Intervention for Psychosis Services (EIPS) with formal diagnosis of the above conditions 5. If on psychotropic medication, must be on a stable dose for 90 days 6. Enhanced Cardiovascular Disease (CVD) Risk as indicated by metabolic syndrome (NCEP ATP III definition), confirmed at screening by any three of the following: 6.1 Waist circumference over 102 cm (men) or 88 cm (women) 6.2 Blood pressure over 130/85 mmHg or documented hypertension on medication 6.3 Fasting triglyceride level over 1.7 mmol/l 6.4 HDL cholesterol level less than 0.9 mmol/l (men), 1 mmol/l (women) 6.5 HbA1c > 37 mmol/mol (5.5%) or documented Type-2 diabetes (T2D) and on medication 6.6 If on treatment for T2D, hypertension or hyperlipidaemia, must be on stable dose medication for at least 90 days Intervention staff: 1. Peer (support) workers and registered mental health nurses (or other healthcare professionals or practitioners with appropriate training) 2. Based at one of the five sites/Trusts 3. Have been trained and engaged with the PEGASUS programme to deliver (co-facilitate) the PEGASUS intervention for the purposes of this study Mixed 18 Years 75 Years All 40 18 Current key exclusion criteria as of 18/12/2025: Service users who: 1. Are currently admitted to acute psychiatric care (i.e. inpatient admission or current referral to a Crisis & Home Treatment Team) 2. Have a primary diagnosis of alcohol or substance misuse 3. Are awaiting/going through assessment with EIPS but without formal diagnosis 4. Have a diagnosis of an organic mental health disorder (e.g. dementia) 5. Are currently in receipt of a highly structured and/ or multi-goal healthy lifestyle intervention (e.g. an intervention that combines structured diet and exercise goals, or a highly structured research-based intervention such as DIAMONDS or PRIMROSE-A). Note: referral to single goal lifestyle support, as typically provided in the voluntary-sector or as online NHS advice, is considered as part of care as usual and will be assessed in both trial groups 6. Blood pressure or hyperlipidaemia managed outside of primary care 7. Type 1 diabetes Intervention staff: Peer (Support) Workers, registered mental health nurses or other healthcare professionals or practitioners who are not trained for nor delivering the PEGASUS intervention for the purposes of this study. _____ Previous key exclusion criteria: Service users who: 1. Are currently admitted to acute psychiatric care (i.e. inpatient admission or current referral to a Crisis & Home Treatment Team) 2. Have a primary diagnosis of alcohol or substance misuse 3. Are awaiting/going through assessment with EIPS but without formal diagnosis 4. Have a diagnosis of an organic mental health disorder (e.g. dementia) 5. Are currently in receipt of a highly structured and/ or multi-goal healthy lifestyle intervention (e.g. an intervention that combines structured diet and exercise goals, or a highly structured research-based intervention such as DIAMONDS or PRIMROSE-A). Note: referral to single goal lifestyle support, as typically provided in the voluntary-sector or as online NHS advice, is considered as part of care as usual and will be assessed in both trial groups 6. HbA1c > 86 mmol/mol 7. Blood pressure or hyperlipidaemia managed outside of primary care 8. Type 1 diabetes Intervention staff: Peer (Support) Workers, registered mental health nurses or other healthcare professionals or practitioners who are not trained for nor delivering the PEGASUS intervention for the purposes of this study. 2025-08-01T00:00:00.000Z 2026-03-31T00:00:00.000Z Severe mental illness and metabolic syndrome Mental and Behavioural Disorders The PEGASUS intervention is a therapeutic group programme for people with severe mental illness at risk of cardiovascular disease and has been co-produced by peer workers, clinicians, and most importantly people with lived experience. The programme consists of 10 group sessions over the course of 6 months. The duration of each session is 2 hours. Each session consists of the same group of 8-12 people and the same two facilitators; a mental health peer support worker (someone who has lived experience of mental health difficulties and is using such experience in their work to support others) and a health care professional (this might be a nurse, dietician or occupational therapist). Each session will have a focus on different aspects of health and wellbeing that our previous research has identified as important to people with SMI and cardiovascular disease risk. Participants are also offered an ‘onboarding’ session with one of the facilitators in advance of the first group session, and 4 additional one-to-one sessions with the peer support worker over the course of the programme. A reunion session will be offered within 3 months of the programme finishing. Behavioural The datasets generated during and/or analysed during the current study are/will be available upon request from the Study Team, in accordance with the policies and conditions set out by the ethical or legal restrictions. bethan.hatherall@citystgeorges.ac.uk Jessica.catchpole@citystgeorges.ac.uk Available on request Protocol

Study website Migrated from study website field

0e508769-419b-4e62-b5e9-991a81efdbff ae64e40b-031b-4cfc-9124-f96ef3755d99 799204df-3a73-4022-9e5d-6eb2f8ce94e3 33193943-4046-42ed-b670-18d3e783ab7b Yes Participant information sheet 47785 PIS PEGASUS feasibility study v1.1 15Oct24.pdf 9ac28dec-d594-4119-88d4-c9a0e16b2087 true application/pdf 241085 fdee9d5c0d31e98315ac818ffbc7b4a2 Protocol file ISRCTN29596999 Feasibility study protocol_V2.3_2025Nov20 (1).pdf 922d756d-cd07-4750-bd30-244630aef9a1 true application/pdf 714096 9943e25311a4a518b90678655bd1a259 Bethan Hatherall https://orcid.org/0000-0001-8114-9648 Public Scientific

School of Health and Medical Sciences, City St George's University of London, Northampton Square

London United Kingdom EC1V 0HB - bethan.Hatherall@citystgeorges.ac.uk Public Jessica Catchpole https://orcid.org/0000-0001-7901-1797 Public Scientific

(Lived Experience Researcher), School of Health and Medical Sciences, City St George's University of London, Northampton Square

London United Kingdom EC1V 0HB +44(0)7423 637934 Jessica.catchpole@citystgeorges.ac.uk Public City, University of London University/education https://ror.org/04489at23 Non-commercial National Institute for Health and Care Research http://dx.doi.org/10.13039/501100000272 11440256 true Improving quality of life and behaviour that challenges in people with mild to moderate intellectual disability through person-centred solution focused communication (ICONIC) ICONIC Current study objectives as of 16/04/2026: 1. To pilot the adapted DIALOG quality of life scale and intervention (aDIALOG+) and obtain feedback on what aspects of the intervention (including the aDIALOG scale, supporting app, training and manual) worked well or did not work well and suggestions for improvement. 2. To test the psychometric properties of the aDIALOG scale to establish whether the aDIALOG scale is a useful quality of life measure in people with learning disability, and to compare it with the original DIALOG scale in people with mental health issues. 3. To conduct a feasibility study of aDIALOG+ delivered by clinicians from community learning disability services to assess recruitment and retention of service users and clinicians. 4. To conduct a feasibility study of aDIALOG+ delivered by care workers from care homes (supported living or residential care) for people with learning disability to assess recruitment and retention of care homes, care workers and service users. _____ Previous study objectives: 1. To pilot the adapted DIALOG quality of life scale and intervention (aDIALOG+) and obtain feedback on what aspects of the intervention (including the aDIALOG scale, supporting app, training and manual) worked well or did not work well and suggestions for improvement. 2. To test the psychometric properties of the aDIALOG scale to establish whether the aDIALOG scale is a useful quality of life measure in people with learning disability. 3. To conduct a feasibility study of aDIALOG+ delivered by clinicians from community learning disability services to assess recruitment and retention of service users and clinicians. 4. To conduct a feasibility study of aDIALOG+ delivered by care workers from care homes (supported living or residential care) for people with learning disability to assess recruitment and retention of care homes, care workers and service users. Background and study aims This research is part of the ICONIC programme, which aims to improve quality of life and behaviour that challenges in people with mild to moderate learning disability through person-centred solution focused communication. DIALOG+ is an evidence based, face-to-face intervention delivered by health professionals using a tablet, which structures routine care sessions to ensure that care planning is personalised, holistic and co-produced. DIALOG+ involves collaboratively completing a quality-of-life scale and then using those ratings to have a solution focused discussion in order to set actions and improve service user satisfaction. Studies have found that it can enhance the communication between service users and those who support them, and can improve quality of life in people with mental health problems, but it has not been used in people with learning disabilities. We want to make DIALOG+ accessible and suitable for people with learning disability and to use it to help individuals think about things in their life they want to improve (e.g. leisure activities, accommodation) by using resources available to them or their carers. Our aim is to test if it improves quality of life and behaviour. Who can participate? Piloting Study: Service users will be eligible to take part if they are aged 18 or over, have mild or moderate learning disability based on service records/clinical notes, have a current history of behaviour that challenges (at least one incident of self-injurious behaviour, physical or verbal aggression, anger / frustration outbursts, or damage to property in the last 3 months), are living in any setting including the family home and supported living/ residential home, and can provide informed verbal or written consent. Psychometric Testing Study: Service users will be eligible to take part if they are aged 18 or over, have mild or moderate learning disability based on service records / clinical notes, are known to community ID services from participating NHS trusts or to voluntary groups for people with ID, and can provide informed verbal or written consent. Comparison Testing Study: Service users will be eligible to take part if they are aged between 18 and 65 years, are under the care of a community psychiatric team or currently an inpatient in a psychiatric hospital in East London NHS Foundation Trust, have a primary diagnosis of a mental health issue, and can provide informed verbal or written consent. Clinical Services Feasibility Study: Service users will be eligible to take part if they are aged 18 or over, have mild or moderate learning disability based on service records / clinical notes, have a current history of behaviour that challenges (at least one incident of self-injurious behaviour, physical or verbal aggression, anger / frustration outbursts, or damage to property in the last 3 months), are living in any setting including the family home and supported living/ residential home, and can provide informed verbal or written consent. Care Homes Feasibility Study: Service users will be eligible to take part if they are aged 18 or over, have mild or moderate learning disability based on service records / clinical notes, have a current history of behaviour that challenges (at least one incident of self-injurious behaviour, physical or verbal aggression, anger / frustration outbursts, or damage to property in the last 3 months), are residing in supported living or residential care, and can provide informed verbal or written consent. What does the study involve? Comparison Testing Study: A resident trainee, clinical studies officer or a member of the research team will arrange a face-to-face or remote (via Teams or Zoom) meeting with at least 200 service users with any mental health diagnosis (without learning disability) to complete the aDIALOG scale, along with the original DIALOG scale, and some demographic questions (e.g. gender, age, ethnicity, primary mental health diagnosis, how they receive their care and the number of years of treatment). Alternatively, service users can be sent the consent form and questionnaires to complete via email or post. Clinical Services Feasibility Study: In this study, we will be assessing whether it is feasible for clinicians to deliver an adapted version of aDIALOG+ to service users with mild or moderate learning disability who have behaviours that challenge (such as physical or verbal aggression towards others or property, anger / frustration outbursts, and self-injurious behaviour). Our aim is to establish whether it is possible to recruit 8-12 clinicians, 30 service users and 30 participant carers (if applicable) into the study. We will also examine the number of sessions of aDIALOG+ that are delivered over 6 months, the quality of the sessions, and the experiences and views of clinicians, service users and participant carers about the intervention, what worked well and what needs to be improved. We will also examine if there are any potential benefits of the intervention by looking at changes in outcome measures such as behaviour, community participation, quality of life and service use. Care Homes Feasibility Study: In this study, we will be assessing whether it is feasible for care workers to deliver an adapted version of DIALOG+ (aDIALOG+) to service users with mild or moderate learning disability who have behaviours that challenge (such as physical or verbal aggression towards others or property, anger / frustration outbursts, and self-injurious behaviour). What are the possible benefits and risks of participating? For the piloting study, service users and care workers will receive a £20 shopping voucher for participating in the interview/focus group following the 6-week intervention period to thank them for their time, and service users will also receive a £20 voucher after taking part in the psychometric testing study. For the psychometric comparison study service users will receive a £10 voucher for taking part. For the clinical services and care homes feasibility studies, service users, participant carers and care workers will receive a £20 shopping voucher for completing qualitative interviews, and service users will receive £20 after completing the baseline assessment and £20 prior to the 6-month follow-up assessments to thank them for their time. Participant carers and care workers will also receive £20 following completion of the baseline assessment and prior to the 6-month follow-up assessments. By sharing experience and views on the aDIALOG+ software, it will help us to improve it and adapt it for clinicians and care workers who use aDIALOG+ in the future. We know that using the original DIALOG+ intervention improved the quality of life of people with psychosis when they used it face to face and we are hoping we can replicate those benefits in service users with learning disability. Where is the study run from? The research is coordinated at the Unit for Adult Mental Health and Wellbeing, Queen Mary University of London. Dr Afia Ali has overall responsibility for the study and it is sponsored by East London NHS Foundation Trust. When is the study starting and how long is it expected to run for? The piloting study started in January 2026 and is expected to run for 3 months. The psychometric testing study started in July 2025 and is expected to run for 17 months. The comparison testing study started in May 2026 and is expected to run for 12 months. The clinical services and care homes feasibility studies started in May 2026 and are expected to run for 13 months. Who is funding the study? National Institute for Health and Care Research (NIHR) (UK). Who is the main contact? Dr Afia Ali (Chief Investigator) afia.ali@qmul.ac.uk / afia.ali6@nhs.net Miss Laura Miller (Programme Manager) l.miller@qmul.ac.uk / laura.miller58@nhs.net Current primary outcomes as of 16/04/2026: WP1a Piloting: 1. Acceptability of / feedback on the intervention is measured using semi-structured interviews / focus groups after 2-4 weeks. 2. Intervention implementation processes from the perspective of clinicians and care workers are assessed using the NoMAD questionnaire after 2-4 weeks. WP1b Psychometric Testing: 1. Construct and concurrent validity of the aDIALOG scale are measured using the Mini-MANS LD and the WHOQOL Disabilities module and Clinical Outcome in Routine Evaluation- Learning Disability (CORE-LD), 14 item version (measure of psychological distress) at baseline. 2. Test re-test reliability of the aDIALOG scale is measured by completing the scale at baseline and again 24 hours to 1 week later. WP1b Comparison Testing: 1. Reliability of the aDIALOG scale through measuring the internal consistency and comparing to the original DIALOG scale. 2. Validity of the aDIALOG scale measured using evenness of distribution of scores compared to the original DIALOG scale and confirmatory factor analysis. _____ Previous primary outcomes: WP1a Piloting: 1. Acceptability of / feedback on the intervention is measured using semi-structured interviews / focus groups with at 6 weeks. 2. Intervention implementation processes from the perspective of clinicians and care workers are assessed using the NoMAD questionnaire at 6 weeks. WP1b Psychometric Testing: 1. Construct and concurrent validity of the aDIALOG scale are measured using the Mini-MANS LD and the WHOQOL Disabilities module and Clinical Outcome in Routine Evaluation- Learning Disability (CORE-LD), 14 item version (measure of psychological distress) at baseline. 2. Test re-test reliability of the aDIALOG scale is measured by completing the scale at baseline and again 24 hours to 1 week later. Feasibility studies: 1. Changes in behaviour in service users is measured using the Aberrant Behaviour Checklist (ABC) – Irritability subscale at baseline and 6 months Feasibility studies: 1. Quality of life in service users is measured using the 13- item WHOQOL Disabilities module (WHOQOL-DIS) at baseline and 6 months 2. Community and Leisure participation in service users is measured using the Guernsey Community Participation and Leisure Assessment – Revised (GCPLA-R) at baseline and 6 months 3. Changes in psychological distress in service users is measured using the Learning Disability – Clinical Outcomes in Routine Evaluation, 14 item version (LD-CORE-14) at baseline and 6 months 4. Changes in the presence of psychiatric disorders in service users is measured using the Moss Psychiatric Assessment Schedule - Check (Moss-PAS Check) at baseline and 6 months 5. Changes in behaviour and functioning in service users as a result of the intervention is measured using a modified version of the Clinical Global Impressions Scale – Improvement version (CGI-I) at 6 months 6. Paid and family carer distress in participant carers is measured using the Kessler Psychological Distress Scale - K6 at baseline and 6 months 7. Changes in health-related quality of life in service users is measured using the EuroQol Five Dimensions - Learning Disability modified version of the EQ-5D-3L at baseline and 6 months. A proxy version of the EQ-5D-5L will also be completed by participant carers at baseline and 6 months. 8. Health related quality of life in participant carers is measured using the EQ-5D-5L at baseline and 6 months. 9. Health and social care contacts and medication in service users is measured using a modified version of the Client Services Receipt Inventory (CSRI) at baseline and 6 months. 10. Treatment costs of delivering the intervention are measured using staff time, room bookings and other resource use in participating clinical services and care homes. 11. Intervention implementation processes from the perspective of clinicians and care workers are assessed using the NoMAD questionnaire at 6 months. 12. Recruitment is measured using screening logs of the number of clinicians, care workers and eligible service users who were approached agreed to take part throughout the study at 6 months. 13. Retention is measured using withdrawal forms completed to record clinicians, care workers and service users who drop out of the study and the reasons why, as well as the number of participants that complete the follow-up assessment at 6 months. 14. Intervention adherence is measured using session completion data from the aDIALOG+ app at 6 months. 15. Intervention fidelity is measured using audio/video recordings of sessions, action plans from the aDIALOG+ app and completed session fidelity checklists at 6 months. 16. Acceptability of the intervention is measured using semi-structured interviews / focus groups with at 6 months. Ethics approval required South West - Cornwall & Plymouth Research Ethics Committee

2 Redman Place, Stratford

London United Kingdom E20 1JQ 25/SW/0055 10.1186/ISRCTN11440256 349711 CPMS: 68145, NIHR: 205440 349711 68145 205440 Interventional non-randomized Interventional Non randomised study Treatment 2027-06-01T00:00:00.000Z United Kingdom England East London NHS Foundation Trust

Robert Dolan House 9 Alie Street

London England E1 8DE RWK@2.16.840.1.113883.2.1.3.2.4.18.48 Cornwall Partnership NHS Foundation Trust

Carew House Beacon Technology Park Dunmere Road

Bodmin England PL31 2QN RJ8@2.16.840.1.113883.2.1.3.2.4.18.48 North London NHS Foundation Trust

Camden Learning Disability Service 5 Pancras Square

London England N1C 4AG Cambridgeshire and Peterborough NHS Foundation Trust

Elizabeth House Fulbourn Hospital Fulbourn

Cambridge England CB21 5EF RT1@2.16.840.1.113883.2.1.3.2.4.18.48 Derbyshire Healthcare NHS Foundation Trust

Trust Headquarters Kingsway Hospital Kingsway

Derby England DE22 3LZ RXM@2.16.840.1.113883.2.1.3.2.4.18.48 Hampshire and Isle of Wight Healthcare NHS Foundation Trust

Tatchbury Mount Hospital Calmore

Southampton England SO40 2RZ RW1@2.16.840.1.113883.2.1.3.2.4.18.48 Rotherham Doncaster and South Humber NHS Foundation Trust

Woodfield House Tickhill Road

Doncaster England DN4 8QN RXE@2.16.840.1.113883.2.1.3.2.4.18.48 Livewell Southwest

Local Care Centre 200 Mount Gould Road

Plymouth England PL4 7PY NR501@2.16.840.1.113883.2.1.3.2.4.18.48 South West Yorkshire Partnership Teaching NHS Foundation Trust

Trust Headquarters Fieldhead Hospital Ouchthorpe Lane

Wakefield England WF1 3SP RXG@2.16.840.1.113883.2.1.3.2.4.18.48 Bradford District Care NHS Foundation Trust

New Mill Victoria Road Saltaire

Shipley England BD18 3LD TAD@2.16.840.1.113883.2.1.3.2.4.18.48 Norfolk Community Health and Care NHS Trust

Research Office, Ground Floor, West Pottergate Medical Centre, Earlham Road

Norwich England NR2 4BX Dane View Care Home with Nursing

165 Glenfield Road

Leicester England LE3 6DP VNC2X@2.16.840.1.113883.2.1.3.2.4.18.48 Central and North West London NHS Foundation Trust

Northwick Park Hospital, Mental Health Unit, Watford Road

Harrow England HA1 3UJ Patient Current key inclusion criteria as of 01/09/2026: WP1a: Service Users Inclusion Criteria: 1. Aged 18 years or over 2. Mild or moderate ID based on service records / clinical notes 3. Current history of behaviour that challenges (at least one incident of self-injurious behaviour, physical or verbal aggression, anger / frustration outbursts, or damage to property in the last 3 months) 4. Living in any setting including the family home and supported living/residential home 5. Can provide informed verbal or written consent WP1b Psychometric Testing: Service Users Inclusion Criteria: 1. Aged 18 years or over 2. Mild or moderate ID based on service records / clinical notes 3. Are known to community ID services from participating NHS trusts or to voluntary groups for people with ID 4. Can provide informed verbal or written consent WP1b Comparison Testing: Service Users Inclusion Criteria: 1. Aged between 18 and 65 years 2. Under the care of a community psychiatric team or currently an inpatient in a psychiatric hospital in East London NHS Foundation Trust 3. Have a primary diagnosis of a mental health issue 4. Can provide informed verbal or written consent WP2: Service Users Inclusion Criteria: 1. Aged 18 years or over 2. Mild or moderate ID based on service records / clinical notes 3. Current history of behaviour that challenges (at least one incident of self-injurious behaviour, physical or verbal aggression, anger / frustration outbursts, or damage to property in the last 3 months) 4. Living in any setting including the family home and supported living/residential home 5. Can provide informed verbal or written consent WP3: Service Users Inclusion Criteria: 1. Aged 18 years or over 2. Mild or moderate ID based on service records / clinical notes 3. Current history of behaviour that challenges (at least one incident of self-injurious behaviour, physical or verbal aggression, anger / frustration outbursts, or damage to property in the last 3 months) 4. Residing in supported living or residential care 5. Can provide informed verbal or written consent WP1a Clinicians Inclusion Criteria: 1. Aged 18 or over 2. Currently working within a community ID service, intensive support team or in a local authority or social care organisation for people with ID 3. From any profession (e.g. psychology, nursing, speech and language therapy, psychiatry, social work), with a minimum of six months experience working with people with ID 4. Consent to participation WP2 Clinicians Inclusion Criteria: 1. Aged 18 or over 2. Currently working within a community ID service, intensive support team or in a local authority or social care organisation for people with ID 3. From any profession (e.g. psychology, nursing, speech and language therapy, psychiatry, social work), with a minimum of six months experience working with people with ID 4. Consent to participation WP3 Care Workers Inclusion Criteria: 1. Aged 18 or over 2. Have worked in the care home for at least three months 3. Provide at least one day of support per week to service users 4. Consent to participation _____ Previous inclusion criteria as of 16/04/2026: WP1a: Service Users Inclusion Criteria: 1. Aged 18 years or over 2. Mild or moderate ID based on service records / clinical notes 3. Current history of behaviour that challenges (at least one incident of self-injurious behaviour, physical or verbal aggression, temper tantrums / outbursts, or damage to property in the last 3 months) 4. Living in any setting including the family home and supported living/residential home 5. Can provide informed verbal or written consent WP1b Psychometric Testing: Service Users Inclusion Criteria: 1. Aged 18 years or over 2. Mild or moderate ID based on service records / clinical notes 3. Under community ID services from the East London Foundation Trust - Updated 04/11/2025: from participating NHS trusts 4. Can provide informed verbal or written consent WP1b Comparison Testing: Service Users Inclusion Criteria: 1. Aged between 18 and 65 years 2. Living in the community and treated as out-patients by community psychiatric teams from participating NHS trusts 3. Have a primary diagnosis of a mental health issue 4. Can provide informed verbal or written consent WP2: Service Users Inclusion Criteria: 1. Aged 18 years or over 2. Mild or moderate ID based on service records / clinical notes 3. Current history of behaviour that challenges (at least one incident of self-injurious behaviour, physical or verbal aggression, temper tantrums / outbursts, or damage to property in the last 3 months) 4. Living in any setting including the family home and supported living/residential home 5. Can provide informed verbal or written consent WP3: Service Users Inclusion Criteria: 1. Aged 18 years or over 2. Mild or moderate ID based on service records / clinical notes 3. Current history of behaviour that challenges (at least one incident of self-injurious behaviour, physical or verbal aggression, temper tantrums / outbursts, or damage to property in the last 3 months) 4. Residing in supported living or residential care 5. Can provide informed verbal or written consent _____ Previous inclusion criteria: WP1a 1. Service Users Inclusion Criteria: 1. Aged 18 or over 2. Mild or moderate ID based on service records / clinical notes 3. Current history of behaviour that challenges (at least one incident of self-injurious behaviour, physical aggression or damage to property in the last 3 months) 4. Living in any setting including the family home and supported living/residential home 5. Can provide informed verbal or written consent 2. Clinicians Inclusion Criteria: 1. Aged 18 or over 2. Currently working within a community ID service, intensive support team or in a local authority or social care organisation for people with ID 3. From any profession (e.g. psychology, nursing, speech and language therapy, psychiatry, social work), grade 4 and above with a minimum of six months experience working with people with ID 4. Consent to participation 3. Care Workers Inclusion Criteria: 1. Aged 18 or over 2. Have worked in the care home for at least three months 3. Provide at least one day of support per week to service users 4. Consent to participation WP1b 1. Service Users Inclusion Criteria: 1. Aged 18 or over 2. Mild or moderate ID based on service records / clinical notes 3. Under community ID services from the East London Foundation Trust - Updated 04/11/2025: from participating NHS trusts 4. Can provide informed verbal or written consent WP2 1. Service Users Inclusion Criteria: 1. Aged 18 or over 2. Mild or moderate ID based on service records / clinical notes 3. Current history of behaviour that challenges (at least one incident of self-injurious behaviour, physical aggression or damage to property in the last 3 months) 4. Living in any setting including the family home and supported living/residential home 5. Can provide informed verbal or written consent 2. Clinicians Inclusion Criteria: 1. Aged 18 or over 2. Currently working within a community ID service, intensive support team or in a local authority or social care organisation for people with ID 3. From any profession (e.g. psychology, nursing, speech and language therapy, psychiatry, social work), grade 4 and above with a minimum of six months experience working with people with ID 4. Consent to participation 5. Have not participated in other work packages 3. Participant Carers Inclusion Criteria: 1. Aged 18 or over 2. Are paid or unpaid (e.g. family carer); if a paid carer, need to have worked with the person for at least six months and should know the person well and support the person on a regular basis 3. Consent to participation WP3 1. Service Users Inclusion Criteria: 1. Aged 18 or over 2. Mild or moderate ID based on service records / clinical notes 3. Current history of behaviour that challenges (at least one incident of self-injurious behaviour, physical aggression or damage to property in the last 3 months) 4. Residing in supported living or residential care 5. Can provide informed verbal or written consent 2. Care Homes Inclusion Criteria: 1. Supported living or residential placements for service users with ID in the participating areas 2. Service manager has agreed for the care home to take part 3. Care Workers Inclusion Criteria: 1. Aged 18 or over 2. Have worked in the care home for at least three months 3. Provide at least one day of support per week to service users 4. Consent to participation 5. Have not participated in other work packages Mixed 18 Years 100 Years All 502 472 Current key exclusion criteria as of 01/09/2026: WP1a Clinicians Exclusion Criteria: 1. Under 18 years of age 2. Not currently working within a community ID service, intensive support team or in a local authority or social care organisation for people with ID 3. Less than 6 months experience working with people with ID 4. Do not consent to participation WP1b Psychometric Testing: Service Users Exclusion Criteria: 1. Under 18 years of age 2. Severe ID based on service records/clinical notes 3. Not known to community ID services from participating NHS trusts or to voluntary groups for people with ID 4. Unable to provide informed verbal or written consent WP1b Comparison Testing: 1. Under 18 years of age and over 66 years of age 2. Do not have a primary mental health diagnosis (e.g., substance misuse disorder) 3. Unable to provide informed verbal or written consent WP2 Clinicians Exclusion Criteria: 1. Under 18 years of age 2. Not currently working within a community ID service, intensive support team or in a local authority or social care organisation for people with ID 3. Less than 6 months experience working with people with ID 4. Do not consent to participation WP3 Care Workers Exclusion Criteria: 1. Under 18 years of age 2. Have worked in the care home for less than 3 months 3. Do not provide at least one day of support per week to service users 4. Do not consent to participation _____ Previous exclusion criteria as of 16/04/2026: WP1b Psychometric Testing: Service Users Exclusion Criteria: 1. Under 18 years of age 2. Severe ID based on service records/clinical notes 3. Not under community ID services from the East London Foundation Trust - Updated 04/11/2025: from participating NHS trusts 4. Unable to provide informed verbal or written consent WP1b Comparison Testing: 1. Under 18 years of age and over 66 years of age 2. Currently in an inpatient in a psychiatric hospital 3. Do not have a primary mental health diagnosis (e.g., substance misuse disorder) 4. Unable to provide informed verbal or written consent _____ Previous exclusion criteria: WP1a 1. Service Users Exclusion Criteria: 1. Under 18 years of age 2. Severe ID based on service records / clinical notes 3. Likely to move out of borough within the next 3 months or at imminent risk of hospital admission 4. Unable to provide informed verbal or written consent 2. Clinicians Exclusion Criteria: 1. Under 18 years of age 2. Not currently working within a community ID service, intensive support team or in a local authority or social care organisation for people with ID 3. Below grade 4 and less than 6 months experience working with people with ID 4. Do not consent to participation 3. Care Workers Exclusion Criteria: 1. Under 18 years of age 2. Have worked in the care home for less than 3 months 3. Do not provide at least one day of support per week to service users 4. Do not consent to participation WP1b 1. Service Users Exclusion Criteria: 1. Under 18 years of age 2. Severe ID based on service records / clinical notes 3. Not under community ID services from the East London Foundation Trust - Updated 04/11/2025: from participating NHS trusts 4. Unable to provide informed verbal or written consent WP2 1. Service Users Exclusion Criteria: 1. Under 18 years of age 2. Severe ID based on service records / clinical notes 3. Already participating in WP3 or involved in another clinical trial 4. Likely to move out of borough within the next 6 months or at imminent risk of hospital admission 5. Unable to provide informed verbal or written consent 2. Clinicians Exclusion Criteria: 1. Under 18 years of age 2. Not currently working within a community ID service, intensive support team or in a local authority or social care organisation for people with ID 3. Below grade 4 and less than 6 months experience working with people with ID 4. Do not consent to participation 5. Have participated in other work packages 3. Participant Carers Exclusion Criteria: 1. Under 18 years of age 2. If a paid carer and have worked with the person for less than six months and/or do not know the person well and/or support the person on a regular basis 3. Do not consent to participation WP3 1. Service Users Exclusion Criteria: 1. Under 18 years of age 2. Severe ID based on service records / clinical notes 3. Already participating in WP2 or involved in another clinical trial 4. Likely to move out of the care home within the next six months or are at imminent risk of hospital admission 5. Unable to provide informed verbal or written consent 2. Care Homes Exclusion Criteria: 1. Not supported living or residential placements for service users with ID and/or not in the participating areas 2. Service manager does not agree for the care home to take part 3. Care Workers Exclusion Criteria: 1. Under 18 years of age 2. Have worked in the care home for less than 3 months 3. Do not provide at least one day of support per week to service users 4. Do not consent to participation 5. Have participated in other work packages 2025-08-07T00:00:00.000Z 2026-11-30T00:00:00.000Z Mild to moderate intellectual disability Mental and Behavioural Disorders Current interventions as of 16/04/2026: An adapted version of DIALOG+ (a brief, low-cost solution-focused intervention that improves the therapeutic effectiveness of routine clinical meetings between patients and clinicians) for individuals with learning disability will be piloted for 2-4 weeks, the adapted scale tested for psychometric properties at 2 timepoints (within 24 hours-1 week) and comparison tested with the original DIALOG scale, and delivered in clinical and care home feasibility studies for 6 months. _____ Previous interventions: An adapted version of DIALOG+ (a brief, low-cost solution-focused intervention that improves the therapeutic effectiveness of routine clinical meetings between patients and clinicians) for individuals with learning disability will be piloted for 4-6 weeks, tested for psychometric properties at 2 timepoints (within 24 hours-1 week), and delivered in clinical and care home feasibility studies for 6 months. Behavioural Data sharing statement to be made available at a later date Protocol

086586ae-3919-40ae-b565-48eaf7fd7840 5bfd6e0a-f6be-42db-af32-79e65800296e 174d80bc-3550-48b2-8785-521553bef35e bd3c8ad4-709e-4148-8736-f221f3b481aa No Protocol file 47564 ICONIC_ WP1 2 and 3 Protocol v1.0 30.05.2025.pdf 6003dfb0-844c-4af6-a553-045bcb24459d true application/pdf 651827 4568e0d65fbd906a796445e923b512a4 Protocol file ISRCTN11440256_PROTOCOL_V3.0_14Oct2025.pdf 7969177c-3c73-44d2-8686-e72b1ec0a78e true application/pdf 746942 3152c1ad486bbc76c7d41a04e951bc25 Protocol file ISRCTN11440256_WP1 2 and 3_PROTOCOL_V5.0_02Apr2026.pdf 4f2b9443-e9af-4f49-9086-51d2b8b13c3d true application/pdf 784320 096cbe3095124bcd27c3728b1f59aa94 Protocol file ISRCTN11440256 ICONIC_WP1 2 and 3 protocol v7.0 07.08.2026.pdf f4e82e02-6c9d-4771-b8bb-e7ce9f38ac7b true application/pdf 679559 508e1db2b92f3a1d7372b6369bbd9c49 Protocol file ISRCTN11440256_PROTOCOL_V8.0_16Sep2026.pdf e806e700-96ca-4eec-b82d-e3047e0cc8a3 true application/pdf 785067 5b5323785ca6ea45878d669d18fae9a0 Laura Miller https://orcid.org/0000-0001-8802-3554 Public Scientific

Unit for Adult Mental Health and Wellbeing Centre for Psychiatry and Mental Health (CPMH) Wolfson Institute of Population Health Queen Mary University of London Yvonne Carter Building, 58 Turner Street

London United Kingdom E1 2AB +44 7352 980401 l.miller@qmul.ac.uk Public Afia Ali https://orcid.org/0000-0002-0104-9370 Principal investigator

Unit for Adult Mental Health and Wellbeing Centre for Psychiatry and Mental Health (CPMH) Wolfson Institute of Population Health Queen Mary University of London Yvonne Carter Building, 58 Turner Street

London United Kingdom E1 2AB +44 7836 584017 afia.ali@qmul.ac.uk Public North East London NHS Foundation Trust Hospital/treatment centre https://ror.org/023e5m798 Non-commercial NIHR Central Commissioning Facility (CCF) 20868432 true Being kind to ourselves: A randomised controlled trial of compassion focused therapy (CFT) to improve symptoms of depression and anxiety in dementia Secondary study objectives: The aims/objectives will be to: 1. Evaluate the efficacy of CFT in improving depression (primary outcome, measured by the Cornell Scale for Depression in Dementia, anxiety, quality of life, cognition, self-compassion, and the caregiver-patient relationship in people with dementia, compared to TAU; at 16 weeks and 6 months. 2. Evaluate caregiver burden and caregiver perception of the caregiver-patient relationship (if caregiver is available to participate), compared to TAU, at 16 weeks and 6 months. 3. Assess the cost-effectiveness of group CFT compared to TAU at 16 weeks by estimating the incremental cost per ‘Quality Adjusted Life Year’ (QALY) gained. 4. Explore: 4.1. Differences in outcomes between face-to-face and online groups 4.2. Participants’ preferences for delivery format and 4.3. Potential predictors of success in the intervention (such as baseline mood, cognitive impairment, engagement (or not) of a caregiver and demographic factors) as part of a secondary, exploratory analysis. Previous study objectives: As this is an unpowered feasibility study, we are not hypothesising significant changes in any outcomes. However, we will explore changes in outcomes pre- and post-intervention, comparing the treatment and control groups (TAU), and may expect some positive trends. We are also exploring the differences between online and f2f groups and have no current hypothesis in terms on superiority. The main objectives of the study are: 1. To undertake a feasibility Randomised Controlled Trial (RCT) to assess critical elements of a full RCT of Compassion Focused Therapy (CFT) in dementia. These include eligibility rates, recruitment and attrition rates, data collection and intervention delivery; 2. To establish acceptability of CFT as an online or face-to-face intervention for people with dementia; 3. To assess intervention fidelity; 4. To establish preliminary intervention efficacy; 5. To establish suitability of study outcome measures including cost-effectiveness measures; 6. To gather data to inform the decision of the primary outcome for a full RCT and obtain estimates of parameters to inform the calculation of the required sample size for a full RCT; 7. To use qualitative and quantitative findings to modify the treatment manual (if required). Background and study aims Of the 850,000 people with dementia in the UK, many experience depression, anxiety or both. This can worsen cognition (e.g., memory and language) and behavioural problems, lead to relationship difficulties, and increase care home admissions. With medications for mood in dementia often ineffective, recent trends have moved towards nondrug interventions. However, the lack of interventions available with proven effects results in significant unmet needs. Compassion Focused Therapy is a talking therapy which addresses feelings of shame and stigma. Our team tested Compassion Focused Therapy with seven people with dementia, finding small improvements in depression, anxiety and self-criticism. One person said: “I have accepted the fact that I have a ‘memory problem’ and am happy being me. I do not blame myself anymore for something that’s not my fault.” This project will assess Compassion Focused Therapy in the form of a randomised controlled trial, following encouraging results from our feasibility study. Participants will be randomly allocated to either the intervention (twelve sessions of group Compassion Focused Therapy, delivered online or face-to-face) or the control group (usual care only). The outcome measures will be depression, anxiety, quality of life, cognition, self-compassion, relationship between caregiver and caregiver burden (where relevant) and costs, measured before and after the intervention period. These will be assessed at the start of the study, after the intervention, and at the 6-month follow-up. We will also explore participants’ preferences for how the therapy is delivered, differences between online and face-to-face groups, and factors that may influence how well the intervention works. This randomised controlled trial builds directly on our earlier feasibility study, with that data included as part of the final analysis. Our aim is to see whether Compassion-Focused Therapy helps people with dementia who are experiencing low mood and whether it is a cost-effective approach. Who can participate? A person can put themselves forward to the research team if they: 1. Have been diagnosed with mild to moderate dementia 2. Experience symptoms of anxiety or depression 3. Have capacity to consent to take part in research 4. Can communicate in English 5. Have access to WiFi, enabling them to partake in online Compassion Focused Therapy groups, OR the ability to attend a face-to-face group 6. Are not participating in another interventional research programme concurrently 7. Have sufficient hearing to engage in group discussions (with or without hearing aids) 8. Aged 18 years and over 9. People can be included whether or not they have a caregiver What does the study involve? If a participant chooses to take part, they will be randomly assigned to either the Compassion Focused Therapy group or a ‘control’ group. There is an equal, 50/50 chance of them being in either group. If they are in the control group, they will not receive any additional treatment. The participants' preference towards virtual or face-to-face meetings will be recorded and we will aim to allocate delivery of these Compassion Focused Therapy sessions accordingly. If the participant is randomly allocated to the intervention group, they will be invited to attend twelve, 60-minute online or face-to-face small group Compassion Focused Therapy sessions. These will occur once a week for twelve weeks. The sessions will involve meeting with a clinical professional and other people with dementia to discuss topics such as low mood, memory problems, and coping mechanisms. During the sessions the participant will also do activities such as gentle breathing and self-compassion exercises. There will be time to reflect as a group on the emotional experience of living with dementia. Sessions will end with suggesting home practices, with participants given session summaries. There will be time for social interaction before and after the session, either over a video conference platform or face-to-face. If the participant is randomised to the Compassion Focused Therapy group, we will run a brief workshop for carers/supporters (if applicable) around the beginning of the Compassion Focused Therapy programme. This will provide information on the principles of Compassion Focused Therapy, an outline of what we intend to do in sessions and tips on what can be done at home to support the person receiving therapy in between sessions. Regardless of which group the participant is allocated to (Compassion Focused Therapy or control), they will continue to have access to their usual care, including input from health and social care professionals, dementia medication, and their usual day activities. Following discussion of any questions they may have with a researcher and signing the consent form, all participants will be asked to: 1. Meet with a researcher for approximately 1.5 hours to answer questions about their mood, anxiety, quality of life, and thinking. If applicable, we will also invite carers/supporters to attend this meeting. 2. Meet with a researcher again after the 12 Compassion-Focused Therapy sessions to answer the same questions as before and again 6 months after the initial assessment. Each follow-up will take approximately 1.5 hours. What are the possible benefits and risks of participating? We appreciate that when an individual experiences memory problems, it may be hard to talk about things like mood and quality of life. The researchers carrying out the assessment, intervention, and interview have clinical experience and are working under supervision. The participant will be encouraged but never forced to take part in a particular activity during the sessions. Overall, the risks of taking part in this study are minimal. However, some people find that certain types of therapy do not help them or make them feel worse. If a participant finds any part of the study distressing, let us know and we can try to resolve the difficulty together or discuss other options of support. The participant is always free to withdraw from the study at any point. If the participant loses capacity to consent, they will be withdrawn from the study and no further data will be collected; however, data collected up until that point will be retained for use in the study. Withdrawing from the study will not affect the standard of care the participant receives. If a participant takes part in the study and is allocated to the intervention group, we hope that their attendance at the sessions is a helpful experience. Previous research into compassion suggests that people can experience greater awareness, acceptance, control, improved coping and wellbeing. Regardless of whether the participant receives the intervention or not, the information we get from this study may help us to support people with dementia and their carers/supporters better in future. Where is the study run from? Recruitment will primarily take place through the NHS Foundation Trusts of North East London, Oxford Health, Norfolk and Suffolk, Black Country Healthcare, Central and North West London, Lincolnshire Partnership, Cheshire and Wirral Partnership and Devon Partnership. We will also recruit through ‘Join Dementia Research’, an online recruitment platform. When is the study starting and how long is it expected to run for? November 2023 to October 2028 Who is funding the study? National Institute for Health and Research, the Research for Patient Benefit Programme (UK) Who is the main contact? Melissa Melville, Melissa.melville@nelft.nhs.uk Current primary outcomes as of 26/03/2026: Symptoms of depression measured by the Cornell Scale for Depression in Dementia (Cornell) at 16 weeks (post-intervention) Previous primary outcomes: Feasibility outcomes: 1. Feasibility of recruitment and retention, assessed by: 1.1. Successful recruitment of the target sample (50 people) in 14-months 1.2. Retention rate of at least 75% of participants to 16 week follow up. We will also evaluate how feasible it is to recruit anxious people to a group intervention how anxiety impacts upon uptake. 2. Acceptability of the intervention, assessed by: 2.1. Overall attendance and retention rates amongst the CFT participants (over 60%) 2.2. Any negative or adverse events related to the intervention 2.3. Level of engagement in the sessions, measured using participation forms developed alongside the CFT manual, (d) preference of virtual or face-to-face. 3. Fidelity, assessed by: 3.1. Therapist completion of the fidelity checklist following each session and 3.2. Audio recording all sessions and an independent researcher rating fidelity with a random 10% of the recordings. A total, mean fidelity score and percentage will be calculated for each CFT session. These scores will be compared across site and provider. We will also compare self-report with observer ratings, providing some idea about the utility of self-report in a future trial. Current secondary outcomes as of 26/03/2026: 1. Symptoms of depression measured by the Cornell Scale for Depression in Dementia (Cornell) at 6 months 2. Symptoms of anxiety measured by the Rating Anxiety in Dementia Scale (RAID) at 16 weeks (post-intervention) and 6 months 3. Quality of life and proxy quality of life measured by the Dementia Quality of Life Scale (DEMQOL) at 16 weeks (post-intervention) and 6 months 4. Health-related quality of life measured by the EQ-5D-5L at 16 weeks (post-intervention) and 6 months 5. Cognitive function measured by the Montreal Cognitive Assessment (MoCA) at 16 weeks (post-intervention) and 6 months 6. Self compassion measured by the Short Self-Compassion Scale (SCS-SF) at 16 weeks (post-intervention) and 6 months 7. Relationship with caregiver measured by the Quality of Caregiver and Patient Relationship scale (QCPRS) at 16 weeks (post-intervention) and 6 months 8. Resource use measured by the Client Service Receipt Inventory (CSRI) at 16 weeks (post-intervention) and 6 months 9. Relationship with caregiver, from both the perspective of the person with dementia and the caregiver, measured by the 10. Quality of Caregiver and Patient Relationship scale (QPCR) at 16 weeks (post-intervention) and 6 months 11. Caregiver burden measured by the Zarit Burden Interview (ZBI) at 16 weeks (post-intervention) and 6 months Previous secondary outcomes: 1. Symptoms of depression are measured by the Cornell Scale for Depression in Dementia, at baseline (pre-intervention), 16 weeks (post-intervention) and 6 months. 2. Symptoms of anxiety is measured using the Rating Anxiety in Dementia Scale (RAID) scale, at baseline (pre-intervention), 16 weeks (post-intervention) and 6 months 3. Quality of life is measured using the EQ-5D-5L scale, at baseline (pre-intervention), 16 weeks (post-intervention) and 6 months 4. Quality of life is measured using the DEMQOL scale, DEMQOL-proxy is collected from the carer (if available), at baseline (pre-intervention), 16 weeks (post-intervention) and 6 months 5. Carer burden is measured using the Zarit Burden Interview scale, at baseline (pre-intervention), 16 weeks (post-intervention) and 6 months 6. Resource use is measure by the Client Service Receipt Inventory, at baseline (pre-intervention), 16 weeks (post-intervention) and 6 months 7. Relationship with caregiver is measured by the Quality of Caregiver and Patient Relationship scale (QCPR) at baseline (pre-intervention), 16 weeks (post-intervention) and 6 months 8. Self compassion is measured by the Short-Self-Compassion Scale (SCS-SF), at baseline (pre-intervention), 16 weeks (post-intervention) and 6 months 9. Cognitive function is measured by the Montreal Cognitive Assessment (MoCA), at baseline (pre-intervention), 16 weeks (post-intervention) and 6 months 10. Secondary outcomes also include the post intervention qualitative interviews with carers /supporters, service managers, clinical professionals facilitating CFT and participants receiving CFT. Qualitative interviews will be used to gather participant, carer/ supporter and clinician perspectives on the value, acceptability and feasibility of the intervention. We will conduct semi-structured, audio-recorded interviews (performed over videoconferencing software or face-to-face) with up to 20 participants with dementia (including up to 10 control group participants with dementia, in order to explore trial procedures from perspective of those who did not participate in the intervention). We will also interview up to 15 carers / supporters (including those who did not attend the workshop to better explore barriers to attendance). We will approach and plan to interview up to 10 NHS personnel (including group facilitators and service managers) for qualitative interviews to determine feasibility of implementation. Qualitative analysis will follow Braun and Clarke’s methods of thematic analysis and will be done using NVivo. Ethics approval required London Riverside

2 Redman Place, Stratford

London United Kingdom E20 1JQ 23/LO/0535 10.1186/ISRCTN20868432 327086 CPMS: 57107, NIHR: 203524 327086 57107 203524 Interventional randomized controlled trial Interventional Randomised controlled trial Treatment 2028-10-31T00:00:00.000Z United Kingdom England Wales North East London NHS Foundation Trust

West Wing C E M E Centre Marsh Way

Rainham England RM13 8GQ RAT@2.16.840.1.113883.2.1.3.2.4.18.48 Oxford Health NHS Foundation Trust

Warneford Hospital Warneford Lane Headington

Oxford England OX3 7JX RNU@2.16.840.1.113883.2.1.3.2.4.18.48 Norfolk and Suffolk NHS Foundation Trust

Drayton High Rd

Norwich England NR6 5BE Black Country Healthcare NHS Foundation Trust

2nd Floor, Trafalgar House, 47-49 King St

Dudley England DY2 8PS Central and North West London NHS Foundation Trust

Trust Headquarters 350 Euston Road Regents PLACE

London England NW1 3AX RV3@2.16.840.1.113883.2.1.3.2.4.18.48 Lincolnshire Partnership NHS Foundation Trust

St George's Long Leys Road

Lincoln England LN1 1FS RP7@2.16.840.1.113883.2.1.3.2.4.18.48 Cheshire and Wirral Partnership NHS Foundation Trust

Trust Headquarters Redesmere The Countess of Chester Health Park Liverpool Road

Chester England CH2 1BQ RXA@2.16.840.1.113883.2.1.3.2.4.18.48 Devon Partnership NHS Trust

Wonford House Hospital Dryden Road

Exeter England EX2 5AF RWV@2.16.840.1.113883.2.1.3.2.4.18.48 Patient Current inclusion criteria as of 26/03/2026: 1. Meet Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) for dementia of any type 2. Mild to moderate dementia as determined by the following: 2.1. A confirmed dementia diagnosis based on DSM-IV criteria for any type of dementia, AND 2.2. A Clinical Dementia Rating (CDR) score of 0.5, 1, or 2 (Morris, 1997). 3. Experience symptoms of depression and/or anxiety as determined by either: 3.1. A HADS score ≥ 8 on the anxiety and/or depression subscale (Zigmond & Snaith, 1983), OR 3.2. A HADS score of 5–7, accompanied by evidence of low mood as reported by a caregiver or clinician, OR 3.3. Significant psychological distress, as assessed by a clinician or researcher, regardless of the HADS score. 4. Have capacity to consent to take part in research 5. Can communicate in English 6. Have access to WiFi, enabling them to partake in virtual CFT groups, OR the ability to attend a face-to-face group 7. Are not participating in another interventional research programme concurrently 8. Have sufficient hearing to engage in group discussions (with or without hearing aids). 9. Aged 18 years and over 10. People can be included whether or not they have a caregiver. Previous inclusion criteria as of 05/09/2024: 1. Meet Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) for dementia of any type 2. Mild to moderate dementia as determined by the Clinical Dementia Rating (CDR) 3. Experience symptoms of depression and/or anxiety (8 ≥) as measured by the Hospital Anxiety and Depression Scale (HADS) OR a minimum score of 5 and experience of depression and/or anxiety as reported by either the caregiver or clinician 4. Have capacity to consent to take part in research 5. Can communicate in English 6. Have access to WiFi, enabling them to partake in virtual CFT groups, OR the ability to attend a face-to-face group 7. Are not participating in another interventional research programme concurrently 8. Aged 18 years and over 9. People can be included whether or not they have a caregiver. Original inclusion criteria: 1. Meet Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) for dementia of any type 2. Mild to moderate dementia as determined by the Clinical Dementia Rating (CDR) 3. Experience symptoms of depression and/or anxiety (8 > = ) as measured by the Hospital Anxiety and Depression Scale (HADS); 4. Have capacity to consent to take part in research; 5. Can communicate in English, 6. Have access to WiFi, enabling them to partake in virtual CFT groups, OR the ability to attend a face-to-face group; 7. Are not participating in another interventional research programme concurrently. 8. Aged 18 years and over 9. People can be included whether or not they have a caregiver. Mixed 18 Years 100 Years All 304 0 1. Communication is significantly impaired by cognitive decline 2. Unable to speak English 3. The participant is currently participating in another interventional research programme. 4. The participant has severe cognitive impairment as measured by the Clinical Dementia Rating scale. 2023-11-08T00:00:00.000Z 2027-09-30T00:00:00.000Z Dementia Mental and Behavioural Disorders Current interventions as of 26/03/2026: This will be a single-blind randomised controlled trial of group CFT versus treatment as usual (TAU). 304 participants will be randomised to either the intervention group or control group (TAU). Randomisation will occur after baseline assessments are completed. Where possible, assessments will be collected by a researcher who is blind to group allocation. Assessments will be delivered virtually or face-to-face, depending on patient preference. Demographics and general information will be collected including age, gender, ethnic group, use of medication (including antidepressants, anxiolytics and cholinesterase inhibitors), treatment preference, participation in other activities and presence / absence of a carer/ supporter. Baseline assessments will include measures of quality of life, symptoms of depression and symptoms of anxiety, a measure of self-compassion, cognitive function, resource use, relationship with caregiver and caregiver burden (if applicable). Each arm will have approximately 150 participants and they will be allocated to one CFT group with up to 7 participants in each group. The duration of the intervention will be 15 weeks, consisting of 12 CFT therapy sessions. Given that it can prove difficult to always fit the 12 sessions into 12 consecutive weeks (due to factors such as weather issues, therapist annual leave, strikes, illness), the additional 3 weeks provides a buffer and may increase the likelihood that participants could receive all 12 sessions. There will be assessments at baseline during the week prior to randomisation, and at the end of the intervention at 16 weeks and at 6 months follow-up. Twelve, 60-minute virtual or face-to-face group CFT sessions including three phases. Phase 1 involves setting up and introducing CFT including psychoeducation on emotion regulation systems, formulation and goal setting. Phase 2 teaches people techniques to develop self-compassion, including imagery and the writing of compassionate letters. Phase 3 teaches techniques to tolerate difficult feelings, focusing on ending and maintaining benefits. Sessions will include a core CFT practice, for example ‘soothing rhythm breathing’ which involves slowing and deepening the breath. Each session will introduce a new concept, such as the qualities of compassion, mindful awareness and understanding the function of self-criticism. There will be time to reflect on the emotional experience of living with dementia, e.g., how the diagnosis can be experienced as a ‘threat’ to the self and future, triggering fear, anxiety and disconnection. Sessions will end with suggesting home practices, with participants given session summaries. CFT will be adapted to compensate for cognitive changes, including frequent repetition and use of visual and verbal information. Building on the experience of running CST groups, groups will consist of approximately five people. We will factor in time for social interaction before and after the session, either virtually or face-to-face. Additional carer/supporter workshop: we will run a brief workshop (flexibility for online or face-to-face) for primary carers/supporters (if available) towards the beginning of the CFT programme. This will educate carers on the principles of CFT, providing an outline of what we intend to do in the sessions and giving people tips on what can be done at home to encourage and support the therapy (for example, reminding the person to do breathing or relaxation exercises). The intervention group will continue to have access to their usual care, which includes input from health and social care professionals, anti-dementia medication and their usual day activities. Control group: Defined as standard treatment available to people with dementia and depression and/or anxiety, which might include medication, other therapies, day care, input from health and social care professionals such as psychiatrists, psychologists and social workers or no treatment. We will collect information on all health and care services used by people with dementia (which we can compare with ongoing observational studies such as IDEAL) to describe what TAU involves for each participant; this can be taken into account in a future, fully powered trial. As both groups will have access to TAU, this study will look at the additional impact of CFT. For those who do not own a tablet and wish to complete the online intervention, ten tablets will be purchased and lent to those participants, aiming to maximise inclusivity. Previous interventions: This will be a single blind, feasibility randomised controlled trial of group CFT versus treatment as usual (TAU). Fifty participants will be randomised to either the intervention group or control group (TAU). Randomisation will occur after baseline assessments are completed. Where possible, assessments will be collected by a researcher who is blind to group allocation. Assessments will be delivered virtually or face-to-face, depending on patient preference. Demographics and general information will be collected including age, gender, ethnic group, use of medication (including antidepressants, anxiolytics and cholinesterase inhibitors), treatment preference, participation in other activities and presence / absence of a carer/ supporter. Baseline assessments will include measures of quality of life, symptoms of depression and symptoms of anxiety, a measure of self-compassion, cognitive function, resource use, relationship with caregiver and caregiver burden (if applicable). Each arm will have approximately 25 participants and they will be allocated to one CFT group with up to 5 participants in each group. The duration of the intervention will be 15 weeks, consisting of 12 CFT therapy sessions. Given that it can prove difficult to always fit the 12 sessions into 12 consecutive weeks (due to factors such as weather issues / therapist annual leave, strikes, illness), the additional 3 weeks provides a buffer and may increase the likelihood that participants could receive all 12 sessions. There will be assessments at baseline during the week prior to randomisation, and at the end of the intervention at 16 weeks and at 6 months follow-up. Twelve, 60-minute virtual or face-to-face group CFT sessions including three phases. Phase 1 involves setting up and introducing CFT including psychoeducation on emotion regulation systems, formulation and goal setting. Phase 2 teaches people techniques to develop self-compassion, including imagery and the writing of compassionate letters. Phase 3 teaches techniques to tolerate difficult feelings, focusing on ending and maintaining benefits. Sessions will begin with a core CFT practice, for example ‘soothing rhythm breathing’ which involves slowing and deepening the breath. Each session will introduce a new concept, such as the qualities of compassion, mindful awareness and understanding the function of self-criticism. There will be time to reflect on the emotional experience of living with dementia, e.g., how the diagnosis can be experienced as a ‘threat’ to the self and future, triggering fear, anxiety and disconnection. Sessions will end with suggesting home practices, with participants given session summaries. CFT will be adapted to compensate for cognitive changes, including frequent repetition and use of visual and verbal information. Building on the experience of running CST groups, groups will consist of approximately five people. We will factor in time for social interaction before and after the session, either virtually or face-to-face. Additional carer/supporter workshop: we will run a brief workshop (flexibility for online or face-to-face) for primary carers/supporters (if available) towards the beginning of the CFT programme. This will educate carers on the principles of CFT, providing an outline of what we intend to do in the sessions and giving people tips on what can be done at home to encourage and support the therapy (for example, reminding the person to do breathing or relaxation exercises). The intervention group will continue to have access to their usual care, which includes input from health and social care professionals, anti-dementia medication and their usual day activities. Control group: Defined as standard treatment available to people with dementia and depression and/or anxiety, which might include medication, other therapies, day care, input from health and social care professionals such as psychiatrists, psychologists and social workers or no treatment. We will collect information on all health and care services used by people with dementia (which we can compare with ongoing observational studies such as IDEAL) to describe what TAU involves for each participant; this can be taken into account in a future, fully powered trial. As both groups will have access to TAU, this study will look at the additional impact of CFT. For those who do not own a tablet and wish to complete the online intervention, ten tablets will be purchased and lent to those participants, aiming to maximise inclusivity. Qualitative interviews will be used to gather participant, carer/supporter and clinician perspectives on the value, acceptability and feasibility of the intervention. Behavioural The datasets generated during and analysed during the current study will be available upon request from Professor Aimee Spector (aimee.spector@nelft.nhs.uk). The data will be pseudonymised and uploaded into a repository. Professor Spector will consult with NELFT as the sponsor on a case-by-case basis regarding each data request received. Available on request 2024 Protocol article in https://pubmed.ncbi.nlm.nih.gov/39627126/ (added 04/12/2024) Protocol

d34c42f7-91a5-4433-a2e9-cc481d5e17d7 a59a7449-72fc-495f-b20f-98dd2fb117c2 d61b73c6-d02a-400a-9d1a-bbc252ca2a16 Yes Participant information sheet 44126 PIS v2.0 08Aug2023.pdf 14a7428e-4c88-41bc-891b-b99b56de1296 true application/pdf 244386 461565e84be2c77e4138bea7676a5a43 Protocol file 44126 CFT_Protocol_V2.0_09.08.23.pdf ed16c5b5-755f-4205-9ae6-2a4d3d82ff6d true application/pdf 1506618 85747b50b0bdaa58d44c13ab8b9b6096 Protocol file ISRCTN20868432_Protocol_V7.0_27Aug2024.pdf 9be35850-a51a-4e41-b823-965c2e9ba1af true application/pdf 708284 f497040bac88eabe665e112dd58b7e33 Participant information sheet ISRCTN20868432_PIS_V3.0_04Oct2023.pdf 2797baae-be93-4879-9b2e-0cf329b5c12a true application/pdf 186747 6649781fefedee9abe86fda8b9b46f5e Protocol file ISRCTN20868432_PROTOCOL_V12_21Jan2026.pdf 63356482-1428-4da8-b39b-4b999bd98896 true application/pdf 949424 9376094a3ab4c0f3a3d6eba1f363dc7b Participant information sheet ISRCTN20868432_PIS_CarerSupporter_V1.0_02Feb2026.pdf 75a170ee-3417-4466-87d4-991b8fbe09bc true application/pdf 281346 0c8cfc7fa8130c04f33ecd822a8059a9 Participant information sheet ISRCTN20868432_PIS_Participant_V1.0_02Feb2026.pdf 24f136d9-ba49-4f5f-9537-a71282f76c59 true application/pdf 288369 9f027482750f4e0a03616b62fc6637a0 Melissa Melville Scientific

North East London Foundation Trust Research and Development Department 1st Floor Maggie Lilley Suite Goodmayes Hospital Barley Lane

Ilford United Kingdom IG3 8XJ +44 300 300 1748 Melissa.melville@nelft.nhs.uk Public North East London NHS Foundation Trust University/education https://ror.org/023e5m798 Non-commercial NIHR Central Commissioning Facility (CCF)