62906561 true A co-produced mental imagery intervention to reduce anxiety in people with mild to moderate intellectual disabilities (Co-MAID): a feasibility study Co-MAID feasibility Primary Objective: To investigate the feasibility of implementing a novel anxiety intervention with 40 patients and up to 20 carers Secondary Objectives: 1. Train 15 intellectual disabilities clinicians (e.g. clinical psychologists, learning disability nurses, psychiatrists, occupational therapists) working within specialist intellectual disabilities and mainstream mental health services to deliver Co-MAID and assess fidelity to the treatment. 2. Implement the manualised intervention in NHS services to determine the acceptability of delivering/receiving the intervention for patients, supporters, and clinicians, respectively. 3. Determine treatment adherence and fidelity. 4. Describe factors that facilitate or challenge the implementation of the intervention through NHS services. 5. Further refine the intervention logic model. 6. Determine feasibility of participant recruitment and retention rates. 7. Assess the feasibility of collecting proposed outcome measures for a definitive trial. 8. Assess the acceptability of randomization for participants, supporters and therapists. 9. Assess the acceptability of linking data between patients and their supporters in a future trial. Background and study aims People with intellectual disabilities have difficulties with their thinking, communication, and completing everyday tasks. Many people with intellectual disabilities are also anxious. This can stop them from going out and seriously affect their relationships. There are talking therapies that help anxious people. However, because people with intellectual disabilities have difficulties with thinking and communication, these therapies cannot be used without being adapted. We have worked with people with intellectual disabilities and their families to adapt the ideas behind talking therapy in a new way by using mental images for those with mild to moderate intellectual disabilities. This new therapy is called 'Co-MAID'. Mental images are the pictures we have in our heads. It is easier for people with intellectual disabilities to change their mental images than their verbal thoughts, to help them feel less anxious. Co-MAID teaches people different ways to change upsetting mental images over 9-12 individual, weekly, hour-long sessions with a therapist. Participants are encouraged to involve a supporter to attend therapy sessions and help with homework. People with intellectual disabilities say that Co-MAID is easy to understand and use. The research aims to: (a) To develop a Co-MAID training package, (b) To check whether Co-MAID can be run in the NHS, (c) To see if a larger study to test whether Co-MAID works is possible. Who can participate? 40 adults (aged 18+ years), with mild to moderate intellectual disabilities and clinical anxiety levels. Participants in the intervention arm may also have a carer involved (up to 20 carers). Five therapists, 10 patients, and 10 supporters will be recruited for the process evaluation. What does the study involve? Adults with mild to moderate intellectual disabilities will be allocated to receive the Co-MAID intervention and treatment-as-usual, or only treatment-as-usual. Co-MAID will be delivered by trained therapists over 9-12 sessions. Participants will complete outcome measures at baseline and follow-up. After the intervention study, people with intellectual disabilities, therapists and supporters will participate in interviews to evaluate Co-MAID feasibility. What are the possible benefits and risks of participating? Participants will receive £15 and reimbursed travel expenses for taking part in the intervention study. Participants may receive a novel anxiety intervention which may be provided to them more quickly than treatment-as-usual. Staff trained in the intervention will have new skills and receive additional training and supervision. There is a risk that participants may find some component of the intervention aversive. However, people with intellectual disabilities and stakeholders have been involved throughout the development and initial testing of this intervention and no aversive experiences have yet been experienced. Risk of distress will be mitigated through the intervention being delivered by an experienced healthcare professional familiar with working with people with intellectual disabilities who has received training in the intervention and will receive ongoing supervision throughout delivery. Where is the study run from? Participants will receive the intervention and complete outcome measures in a clinical or residential setting. The study is being run across five NHS trusts in central and southern England. When is the study starting and how long is it expected to run for? October 2026 to December 2027. Who is funding the study? National Institute for Health and Care Research (NIHR), UK. Who is the main contact? Dr Olivia Hewitt, olivia.hewitt@oxfordhealth.nhs.uk. Anxiety the Adapted General Anxiety Disorder-7 (GAD-7) baseline and follow-up (20 weeks after randomization) Anxiety the Glasgow Anxiety Scale for people with intellectual disabilities (GAS-ID) baseline and follow-up (20 weeks after randomization) Depression the Adapted Patient Health Questionnaire-9 (PHQ-9) baseline and follow-up (20 weeks after randomization) Quality of life the European Quality of Life 5 Dimensions 3 Level version (EQ-5D-3L) baseline and follow-up (20 weeks after randomization) Mental imagery the Mental Imagery Questionnaire for people with intellectual disabilities (MIQ-ID) baseline and follow-up (20 weeks after randomization) Resource use the Client Service Receipt Inventory (CSRI) baseline and follow-up (20 weeks after randomization) Ethics approval required North West - Liverpool Central Research Ethics Committee

2 Redman Place, Stratford

London United Kingdom E20 1JQ 26/NW/0187 10.1186/ISRCTN62906561 349099 CPMS: 64636, NIHR: 208933 349099 64636 208933 Interventional Randomized controlled trial Blinded (masking used) Active Parallel Treatment Not applicable Treatment 2027-12-01T00:00:00.000Z 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 Tatchbury Mount Hospital

Calmore

Southampton England SO40 2RZ Hertfordshire Partnership University NHS Foundation Trust

The Colonnades Beaconsfield Close

Hatfield England AL10 8YE RWR@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 Littlemore Mental Health Centre

Sandford Road Littlemore

Oxford England OX4 4XN RNU30@2.16.840.1.113883.2.1.3.2.4.18.48 false 1. Mild to moderate ID diagnosis confirmed by case note review 2. Existing diagnosis of an anxiety disorder confirmed or initially made at screening 3. Capacity to give informed consent to participate in accordance with the Mental Capacity Act (2005) Mixed 18 Years 120 Years All 40 0 1. Currently receiving another psychological therapy 2. Actively suicidal, experiencing hallucinations or delusions 3. Severe or profound intellectual disability diagnosis 2026-10-01T00:00:00.000Z 2027-05-03T00:00:00.000Z Anxiety in people with mild to moderate intellectual disabilities Mental and Behavioural Disorders Design This study aims to test the feasibility of delivering the Co-MIAD intervention in NHS settings. We are testing this out with 40 adults who have mild to moderate intellectual disabilities and anxiety. We will recruit these people from 5 NHS Trusts. Half will be randomly allocated to receive treatment as usual for anxiety (TAU), and half will receive TAU plus the Co-MAID intervention. This feasibility study is being conducted in advance of a full clinical trial of the intervention. Therefore, we are modelling a number of processes such as collecting information about resources for health economic analysis, and randomisation to allow us to investigate the acceptability of this for participants and therapists. Participants may have a supporter to attend sessions with them and help with any between-session tasks, although this is not mandatory. We will train 15 therapists across the 5 NHS trusts to deliver the Co-MAID intervention. We will capture information about the therapist, such as demographic information, professional background, years of experience etc. Randomisation Patients will be randomised using block randomisation on a 1:1 basis to either the intervention or comparator arm. The randomisation list will be produced in advance and will use a block size of 4. Randomisation will be conducted using R version 4.4.1 (2024-06-14) and the ‘blockrand’ package. The study team will communicate the outcome of randomisation for each participant to the site PI. They will then pass on this information to the participant and therapist. How will participants be recruited? All participants will be recruited through NHS services. Clinicians working in the service will identify people who meet the eligibility criteria (having a mild to moderate intellectual disability and anxiety disorder) by checking waiting lists for the service, discussion with other clinicians, searching electronic patient records and checking referrals coming into the service. Any potentially eligible participants (and their supporter if applicable) will be contacted by clinicians in the service and provided with brief information about the study in an accessible format (this study advert will be co-designed by the CDG). Participants and/or supporters can then contact the study team via two routes: (a) Participants (and supporters) tell clinicians that they want their contact details passed to the study team when asked. The study team will receive the details from clinicians and then contact the participants (and supporters). (b) Participants (and supporters) contact the study team directly using the contact information they were provided. Once they have contacted the study team, a research assistant from the study team (or site R&D) will complete screening to determine eligibility and gather informed consent. Timetable Broadly, Phase 1 involves developing project resources alongside our Co-Design Group (CDG), which will take place during months 1-6. These include a therapist's manual, a training package for therapists, a person's workbook, and fidelity checklists. Recruitment of 40 participants will take place in months 7-12, with the intervention being delivered in months 7-15. Process evaluation (including interviews with participants, supporters and therapists) will be conducted in months 12-19. Dissemination, report writing and feedback to funders will occur in months 19-21. Therefore, for participants taking part in the study, their involvement will last for about 6 months in order to screen them for eligibility, collect baseline data, randomise them and deliver the intervention (if applicable) and collect follow-up data 20 weeks post-randomisation. Data collection Data will be gathered from participants at three time points: (1) screening, (2) baseline assessment within 4-weeks of randomisation, and (3) follow-up assessment within 20-weeks of randomisation. The questionnaires that will be administered at these time points include a measure of anxiety (primary outcome measure) and may also include secondary measures such as (a) anxiety diagnosis, (b) symptoms of depression, (c) challenging behaviour, (d) quality of life, (e) wellbeing, and (f) mental imagery. Several potential outcome measures appropriate for this population will be presented to the Co-Design Group, who will make a recommendation to the study team about which measures should be included. Data will be collected by members of the research team, except for the therapists' rated fidelity checklist, which will be completed by therapists themselves and returned to the study team. We will carry out semi-structured interviews with 10 patients, 10 supporters, and 5 therapists to understand what people thought about the intervention and to understand the facilitators and barriers to delivering this intervention in NHS settings. These interviews will be held online or in the person's home or community setting, depending on personal preference. The interviews will be carried out by the research assistant. Data analysis We will recruit up to 40 patients (20 in each treatment arm), and up to 20 supporters. Five therapists will take part in process evaluation interviews. As this is a feasibility study, and the purpose is to provide estimates of key parameters to inform a future pilot trial rather than to power the current study to detect statistically significant differences, a formal a priori power calculation will not be conducted. Descriptive statistics will be reported for the study. Interviews will be audio-recorded, transcribed and analysed using Template Analysis. PPI Input The proposed research focuses on a feasibility study into Co-MAID. Co-MAID has been co-designed with people with intellectual disability and their family members, along with wider stakeholders. A group of 6-8 people with mild or moderate intellectual disability and their family members have formed our PPI group throughout our research and will continue to guide this feasibility study. PPI has been central to the design and preliminary testing of Co-MAID in NHS settings and disseminating findings from prior research stages. The involvement of a PPI co-applicant, Chrissy Marsh, has been central to this application. CM brings a wealth of expertise as the mother of a person with intellectual disability, and through her previous expertise as a teacher within a special educational school. The decision to apply for a feasibility study was made in collaboration with PPI members, and they have provided extensive feedback and support for this proposal. The research team has met with a PPI group regularly (every 6 weeks) over the past 14 months to develop the current application. This group is very familiar with the Co-MAID intervention, and some members of the PPI group have provided input into the project over the past 6 years (since the original inception of the idea for this intervention). Input from this group has included the development and refinement of the plain English summary, refining the research design, structuring the process evaluation (including the topics to be covered in qualitative interviews), designing and planning the input from the Co-Design Group, and feeding into guidance around membership of this group. PPI input has shaped and developed ideas around dissemination, including the use of a dissemination matrix to ensure the needs of all stakeholders will be addressed, and advocating for various innovative and creative methods of dissemination. Without the consistent support from our PPI partners, this research simply would not have been possible, and we continue to rely on their collaboration at each stage of our work. Behavioural Data sharing statement to be made available at a later date

056951c8-7556-47c5-ae1c-de13dc4e894e 2132027b-d8e5-4c96-bb4b-017c6729efcf 0f458c2e-04cc-46b2-a631-18e76c419578 No Olivia Hewitt https://orcid.org/0000-0002-6393-2388 Principal investigator Scientific Public

Oxford Health NHS Foundation Trust House 2, Slade House, Horspath Driftway, Headington

Oxford United Kingdom OX3 7JH +44 07775 540151 olivia.hewitt@oxfordhealth.nhs.uk Public Oxford Health NHS Foundation Trust Hospital/treatment centre https://ror.org/04c8bjx39 Commercial National Institute for Health and Care Research http://dx.doi.org/10.13039/501100000272 82078351 true Experiences of feeling exceptional: finding meaning and balance in everyday life - a proof-of-concept multiple baseline single case experimental design series testing the feasibility, acceptability, and potential clinical benefits of treating harmful grandiose delusions EOFE To establish a preliminary indication of the clinical effectiveness and acceptability of a novel intervention to reduce harmful grandiose delusions in patients with psychosis attending NHS mental health services. Feedback from this study will be used to refine the therapy in preparation for a subsequent pilot RCT. Background and study aims Experiences of Feeling Exceptional (often called grandiose delusions by mental health services) are false beliefs about having special powers, mission, wealth or identity. They are experienced by one in three patients diagnosed with severe mental health problems. These beliefs can be very meaningful but they can also come at a cost. For example: - Stephen believed he had superpowers. He crashed his car at speed to try to demonstrate his abilities. - Sophie believed that she was God. She stepped off heights as she expected to fly. - Max believed he was an undercover special forces agent. He tried to conduct arrests and got into fights believing that he had back up from other agents. Current talking therapies and medications do not work well enough for many patients with experiences of feeling exceptional. A new understanding of why these experiences persist for a person has been developed and this has been used to develop the first talking therapy specifically for the treatment of harmful experiences of feeling exceptional. The therapy aims to help people find a personally meaningful focus in life but that comes with fewer costs. The current study will conduct the very first test of this therapy. It will assess the acceptability of the therapy for patients, and provide initial evidence concerning whether the therapy is helpful. Who can participate? Adults aged 16+ years who are receiving care from Oxford Health NHS Foundation Trust’s mental health services for the treatment of affective or non-affective psychosis may be eligible to participate. Participants must have held a persistent experience of feeling exceptional for at least 3 months and be able to give informed consent. What does the study involve? Participants will all receive the talking therapy which will be delivered by a psychologist over 16 weekly one-to-one sessions. Before therapy begins, there will be a baseline (waiting) period of 4 to 6 weeks during which participants will complete brief weekly assessments. The length of this baseline period is randomly assigned. This helps researchers understand whether any changes are due to the therapy rather than the passage of time. Participants will complete the brief weekly measures throughout both the baseline and therapy phases. In addition there will be four more detailed assessment points: at the start of the baseline period, end of the baseline period (just before therapy begins), midway through therapy, and at the end of therapy. There will also be a short follow-up assessment after therapy ends. Participants will also be invited to take part in interview to share their experiences of therapy. What are the possible benefits and risks of participating? At present, since the therapy has not been evaluated before, ther eis no way to say that taking part in the study will benefit participants. It is hoped however that the therapy will help people to be able to live a meaningful and purposeful life whilst reducing difficulties associated with their experience of feeling exceptional. The therapy is not currently available outside of the study, and all participants will receive the therapy. No major risks are anticipate any from taking part. The new therapy has been designed to minimise any risks. However, the research team will check whether there are any potential problems over the course of this research study. Everyone will have the research assessments, and if these are experienced as upsetting then it is possible to reduce the length of these or for the person to withdraw. In addition to having the support of the study therapist, participants will continue to have their usual contact with their NHS care team throughout their time in the study who can offer support if participants experience distress. Where is the study run from? The study is being run within Oxford Health NHS Foundation Trust, and led by a research team based in the Department of Experimental Psychology, at the University of Oxford. When is the study starting and how long is it expected to run for? The study is expected to begin recruitment in May 2026 and will run for approximately 13 months including recruitment, therapy delivery, and follow-up. Who is funding the study? The National Institute for Health and Care Research (NIHR), UK. Who is the main contact? Dr Louise Isham (Clinical Psychologist), louise.isham@oxfordhealth.nhs.uk Grandiose delusion severity the Psychotic Symptom Rating Scale - Delusions subscale (PSYRATS delusions) the start of baseline, the end of baseline, the mid therapy, and the end of therapy Grandiosity severity Specific Psychotic Symptom Rating Scale - Grandiosity Subscale (SPEQ-G) the start of baseline, the end of baseline, the mid therapy, and the end of therapy Grandiose delusion conviction a 0-100% Visual Analogue Scale (VAS) weekly timepoints throughout baseline and therapy phases and at two-week follow-up after therapy completion Repetitive thinking about the grandiose delusions the Thinking about Experiences of Feeling Exceptional Questionnaire (TEEQ) the start of baseline, the end of baseline, the mid therapy, and the end of therapy Immersion Behaviours Immersion Behaviours Questionnaire the start of baseline, the end of baseline, the mid therapy, and the end of therapy Meaning in Grandiose Delusions the Grandiosity Meaning Measure (gram) and Grandiosity Meaning Measure - Sources (grams) the start of baseline, the end of baseline, the mid therapy, and the end of therapy Anomalous experiences the Specific Psychotic Experiences Questionnaire - anomalous experiences (SPEQ-AE) the start of baseline, the end of baseline, the mid therapy, and the end of therapy Mania the Internal State Scale the start of baseline, the end of baseline, the mid therapy, and the end of therapy Subjective harm from grandiose delusions the Subjective Harm from Experiences of Feeling Exceptional Questionnaire (SHEEQ) the start of baseline, the end of baseline, the mid therapy, and the end of therapy Brief idiographic measures (single item visual analogue scales) for repetitive thinking, immersion behaviours, meaning from grandiose delusions, anomalous experiences, mania, and subjective harm the Brief single-item visual analogue scales weekly timepoints throughout baseline and intervention phases and at two-week follow-up after the intervention has finished Depression the Patient Health Questionnaire-9 (PHQ-9) the start of baseline, the end of baseline, the mid therapy, and the end of therapy Anxiety the Generalized Anxiety Disorder-7 (GAD-7) the start of baseline, the end of baseline, the mid therapy, and the end of therapy Paranoia the Revised Green et al Paranoid Thought Scale (RGPTS) the start of baseline, the end of baseline, the mid therapy, and the end of therapy Patient satisfaction an Adapted Client Satisfaction Questionnaire the end of therapy Number of patients completing a dose of therapy (8 sessions is considered a dose of therapy) study data collection the end of therapy Participants' experience of therapy qualitative interviews a two-week follow up after the end of therapy Ethics approval required East of England - Cambridge East Research Ethics Committee

2 Redman Place, Stratford

London United Kingdom EC20 1JQ 26/EE/0015 10.1186/ISRCTN82078351 344160 CPMS: 62659 344160 62659 Interventional N/A: single arm study Open (masking not used) Uncontrolled Single Treatment Not applicable 2027-07-14T00:00:00.000Z United Kingdom England Oxford Health NHS Foundation Trust

Littlemore Mental Health Centre Sandford Road Littlemore

Oxford England OX4 4XN RNU@2.16.840.1.113883.2.1.3.2.4.18.48 false 1. Participant is willing and able to give informed consent for participation in the study 2. Aged 16 years or older 3. Attending NHS mental health services for the treatment of affective or non-affective psychosis 4. Persistent (at least 3 months) grandiose delusion (as defined by the Schedules for Clinical Assessment in Neuropsychiatry), held with at least 60% conviction 5. No planned significant medication changes at the outset of participation Mixed 16 Years 110 Years All 9 0 1. A primary diagnosis of another mental health condition (e.g. substance use disorder) that would be the first clinical priority to treat 2. Current engagement in any other intensive individual psychological therapy or a significant change in medication 3. In forensic settings or Psychiatric Intensive Care Unit (PICU) 4. Command of spoken English inadequate for engaging in the therapy 5. Significant learning difficulties that would prevent the completion of assessments or the therapy 6. A participant may also not enter the trial if there is another factor (for example, current active suicidal plans that need to be the focus of intervention), which, in the judgement of the investigator, would preclude the participant from providing informed consent or from safely engaging with the trial procedures. Reason for exclusion will be recorded 2026-07-06T00:00:00.000Z 2027-02-14T00:00:00.000Z Treating persistent harmful grandiose delusions in patients attending NHS mental health services for the treatment of affective or non-affective psychosis. Mental and Behavioural Disorders The intervention is a psychological therapy designed to precisely target the key mechanisms which drive grandiose delusions and reduce associated harm. Central to the therapy is helping patients find alternative sources of meaning in their lives so that the grandiose delusions can fade. The therapy will be provided in up to 16 sessions. The intervention will be delivered by a mental health staff member (e.g. clinical psychologist, counselling psychologist, or CBT therapist) in up to sixteen one-hour one-to-one sessions over 16 weeks. Behavioural Not expected to be made available Protocol

d61fa88c-891e-4b29-a197-a1f943f27221 79bbc29d-a7fa-439d-a256-2bb5e24ee3a0 25fdf95f-8cd0-4ddd-adba-20bb0d7ef13c No Protocol file 49819_Protocol_V1.2_06May2026.pdf 4e591a2a-fce2-4028-af15-85acd9a8d02b true application/pdf 627143 ba15d38b18e51e6e68527eeacc9c7e06 Louise Isham https://orcid.org/0000-0003-1752-5236 Principal investigator Scientific Public

Department of Experimental Psychology University of Oxford The Life and Mind Building South Parks Road

Oxford United Kingdom OX1 3EL +44 01865 283804 louise.isham@psy.ox.ac.uk Public University of Oxford https://ror.org/052gg0110 Non-commercial National Institute for Health and Care Research http://dx.doi.org/10.13039/501100000272 34358183 true Improving Postpartum Outcomes of Severe mental Illnesses in Ethnically diverse mothers (POSIE) POSIE WP2: To gather and understand the lived experience of mothers who have experienced postpartum SMI through photovoice WP3: To co-design a postpartum SMI care pathway system using insight to improve care experiences Background and study aims People from ethnic minority backgrounds experience poorer outcomes in perinatal mental health care, including higher rates of severe mental illness after childbirth and poorer access to appropriate support. These inequalities can have serious consequences for mothers, babies, and families. This study aims to understand why these inequalities occur and how care can be improved. The study focuses on severe mental illnesses that occur during the first year after birth, such as postpartum psychosis, bipolar disorder, severe depression, and other serious mental health conditions. This stage of the study focuses on Work Package 2 (WP2) and Work Package 3 (WP3): WP2 aims to understand the experiences of people who have received care for postpartum severe mental illness by using a creative research method called Photovoice, where participants share photographs, drawings, and stories about their experiences. WP3 aims to bring together people with lived experience, carers, and professionals to use the findings from WP2 and co-design a culturally safe care pathway that could improve future services and reduce inequalities in care. Who can participate? WP2: 1. Adults aged 18 years or over. 2. People who have experienced postpartum severe mental illness and received care within the last five years from a range of ethnic and social backgrounds. WP3: 1. People who have experienced postpartum severe mental illness. 2. Family members, carers, or supporters of someone who has experienced postpartum severe mental illness. 3. Health and social care professionals, voluntary sector staff, policy makers, and other stakeholders involved in perinatal mental health care. What does the study involve? WP2 involves photovoice workshops where participants will share their experiences of postpartum severe mental illness using photographs. WP3 will review findings from earlier parts of the study and discuss the experiences of care to co-design a novel culturally safe care pathway to be implemented in NHS sites nationally. What are the possible benefits and risks of participating? Participants will have the opportunity to share their experiences and help improve future mental health services. The study may contribute to more equitable, culturally safe, and effective care for people affected by postpartum severe mental illness. Some participants may find it rewarding to contribute to research and service improvement. However, it can be upsetting or emotionally difficult to discuss experiences of mental illness and complete confidentiality in group settings cannot be guaranteed. Where is the study run from? The study is coordinated by the University of Oxford, Department of Psychiatry, and is being conducted in collaboration with NHS organisations, universities, charities, and community partners across England (UK) When is the study starting and how long is it expected to run for? September 2025 to November 2028 Who is funding the study? The study is funded by the National Institute for Health and Care Research (NIHR) through its Health and Social Care Delivery Research (HSDR) Programme (UK) Who is the main contact? Prof. Kamaldeep Bhui, kam.bhui@psych.ox.ac.uk Lived experiences, barriers, facilitators, vulnerabilities, and opportunities for improving care for people with postpartum severe mental illness (PP-SMI), thematic analysis of three photovoice workshops over 3 weeks the four study sites (Oxford, London, Sheffield and Lancashire) WP3: positive and negative experiences of the resources from WP1&2, priority setting meetings of 4–6 people the four study sites Development of a culturally safe co-designed postpartum severe mental illness care pathway and implementation plan, two in-person half-day co-design workshops over 2 months each of the four study sites There are no secondary outcomes Ethics approval required Bromley REC

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- United Kingdom - 26/LO/0304 10.1186/ISRCTN34358183 342441 CPMS: 61810, NIHR: 167329 342441 61810 167329 Non-randomized study Interventional Non randomised study Other 2028-11-30T00:00:00.000Z United Kingdom England Oxford Health NHS Foundation Trust

Littlemore Mental Health Centre Sandford Road Littlemore

Oxford England OX4 4XN RNU@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 Sheffield Health Social Care NHS Foundation Trust

Centre Court Atlas Way

Sheffield England S4 7QQ Lancashire and South Cumbria NHS Foundation Trust

Sceptre Point Sceptre Way Walton Summit

Preston England PR5 6AW RW4@2.16.840.1.113883.2.1.3.2.4.18.48 false 1. Aged 18 years or older 2. Able to communicate sufficiently in English or via approved interpretation support to participate meaningfully 3. Willing to take part in the relevant study activities for the work package 4. Have lived experience of receiving care for perinatal severe mental illness (SMI) within the preceding 5 years (from 12 weeks pregnant to up to a year after pregnancy) 5. Willing and able to participate in photovoice workshops (online or in person), including taking or selecting photographs and engaging in group discussion Mixed 18 Years 100 Years All 380 0 1. Individuals who do not have the capacity to provide informed consent 2026-09-01T00:00:00.000Z 2028-11-30T00:00:00.000Z Perinatal severe mental illness Mental and Behavioural Disorders WP2: Exploring patient priorities for postpartum SMI treatment and outcomes Sample size: 60 mothers with experience of postpartum SMI Recruitment: via NHS Trusts and community organisations Procedure: In each site, we will arrange for three consecutive photovoice workshops to be held in a hybrid model of online and carefully chosen creative environments for accessibility and comfort to facilitate discussion. Patients may bring a carer, a family member, friend, or confidante for support. This accompanying person may wish to remain during the workshops, as preferred by the participant, and so we will gather carer views also within the interpretive narratives. The first workshop of between 2 and 3 hours will introduce the research and explain that we are interested in understanding: 1. Experiences and perceptions around postpartum severe mental illness. 2. The causes and complexities of care. 3. Their experiences of care and recommendations. We will provide support and arrange comfort breaks and tailor the process to individual needs. Participants will be given disposable cameras, notebooks and asked to drop them in a central location local to them a week after the workshop. If they choose the online option they may prefer to use their phones and send the images to a project email address, or they can use their own phone even for face to face workshops. In some instances, participants may wish to use existing photographs which they feel reflect their care experiences. As set out, other creative materials will all be considered within the overall process. In the second and third workshops, participants will be presented with their digitised images and guided through reflections to generate narratives and captions for a minimum of 3-5 chosen images (total of 180-300 items). The second workshop will be a session of at least 2 hours, any time within a 6-8 hour time window, and will occur 2 weeks after the first workshop, and a third workshop will be held a week after the second. These times are flexible and can be adjusted around each participant. Prompt questions will be used to elicit their experiences (adapted from Hergenrather, 2009): Describe what you see in this photo and how it makes you feel. Why did you take a photo of this? What does this photo tell us about you? How can it provide opportunities to improve understanding about your illness and life experiences? Do you have suggestions for improving your care? In your care experiences, what helped and what did not work? How can inequalities arise and be reduced? The third workshop will be a group discussion; there will be no topic guide, but the conversation will be generated by which of their images participants wish to share with the rest of the group. The discussion will be facilitated by the research team, and participants will be encouraged to consider two questions: 1. What made a positive difference to your experience? 2. What could have been done differently? All workshops will be co-facilitated with a peer researcher. WP3: Co-design a care pathway to address inequalities in postpartum SMI treatment Sample size: 16 key stakeholders for priority-setting meetings, 80 key stakeholders for co-design days. Recruitment: via NHS Trusts and WP2 contacts and community settings Procedure: The richly contextualised narrative accounts of life-worlds and care experiences of participants from WP2 and WP1 data (CPRD data analysis) will be summarised, using visual and textual materials, to inform co-production of a culturally inclusive care pathway. In a series of priority-setting meetings (3-6 of these) with small groups (3-6 per group), we will review the photovoice outputs to conceptualise ‘touch points’ that characterise positive and negative experiences of patients with a view to generating consensus about the priorities for service improvement (participants). We understand that trust and relationship building are important for a successful co-design process, so we hope to involve the same core participants throughout the events and activities which comprise both of these key co-design phases. For this core group, we will seek to recruit people with lived experience of postpartum severe mental illness, in addition to those involved in priority setting. We aim to ensure there are at least 10 and up to 20 patients, 10 carers, and 25 professional stakeholders. The purpose is to represent multiple intersectional experiences by identity (age, gender, sexuality, neurodivergence) and place characteristics (rural, semi-rural, urban). We will pay these core participants for their time in attending events and participating in co-design activities. Our research staff, including peer researchers, will prioritise relationship building and attending to different needs and preferences of those attending workshops in order to make them a success and a good experience for participants. We will discuss and agree ground rules at the outset of the process, drawn from existing principles of good practice for co-design and user involvement. We will base the process around a series of group meetings. Depending on the composition and preferences of the group, we will consider face-to-face and online as alternatives. WP4: Evaluate the implementation of a postpartum SMI care pathway Sample size: via NHS Trust Recruitment: 5 professionals from each site and 40 mothers who received the intervention at each site. Procedure: The local teams will implement the newly developed care pathways from WP3 with around 40 mothers over 6-9 months at each study site, as well as two additional sites not involved in co-development, to learn about the role of co-design in the adoption of interventions. We will conduct the NoMAD survey before and after implementation and supplement this with interviews at each site to better understand barriers and facilitators to implementation and explore intervention fidelity. WP5: Developing guidance, dissemination and impact Sample size: 40 key stakeholders Recruitment: via NHS Trusts and Community Organisations Procedure: Key stakeholders (people with lived experience, charitable organisations, NHS leaders, healthcare professionals and policymakers) will be convened for a consensus workshop. They will be provided with the culturally inclusive care pathway for postpartum SMI, a proposed implementation strategy and a summary of the implementation evaluation. The workshop will aim to identify the following: 1. Key changes required to existing pathways; 2. the additional resources and expertise used to support the development and revision of existing pathways; 3. the training of staff to support and iterate the pathway over time whilst retaining the ethos and values base; 4. the type and nature of resources required. Behavioural Data sharing statement to be made available at a later date 3057f22a-1a59-4b1b-8ef1-bb3c1f676ec2 69424a9d-cd31-4887-835d-18706dd0f538 0462766f-094d-43e6-83eb-fa6c116d5e15 08989c08-59ba-4c97-b798-1aed64b0505e a6733cbb-51dc-456f-ac8c-8a27c578d602 No Harsimran Sansoy Scientific Public

Department of Psychiatry, University of Oxford, Warneford Hospital

Oxford United Kingdom OX3 7JX - harsimran.sansoy@psych.ox.ac.uk Public Kamaldeep Bhui Principal investigator

Warneford Hospital, Warneford Ln, Headington

Oxford United Kingdom OX3 7JX - kam.bhui@psych.ox.ac.uk Public Roisin Mooney Scientific Public

Warneford Hospital, Warneford Ln, Headington

Oxford United Kingdom OX3 7JX - roisin.mooney@psych.ox.ac.uk Public University of Oxford Hospital/treatment centre https://ror.org/052gg0110 Non-commercial National Institute for Health and Care Research http://dx.doi.org/10.13039/501100000272 74790966 true Randomised parallel trial comparing the efficacy of focused cognitive behavioural therapy versus treatment as usual for obsessive compulsive disorder The primary aim of the present study is to address the following question: Is there a difference in how much participants' OCD symptoms improve between individuals with OCD who receive focused CBT from trained psychological wellbeing practitioners (PWPs) compared to those who receive treatment as usual (TAU) at two NHS Talking Therapies services? The secondary research question is as follows: Is there a difference in how much participants' general mental health improves (anxiety, depression, and general functioning) between individuals with OCD treated with focused CBT compared to TAU? Background and study aims Obsessive compulsive disorder (OCD) is a severe mental health condition that affects around 2.3% of the population. OCD can cause high levels of distress, make it harder for people to cope in their day-to-day lives, and lead to significant healthcare costs. People with OCD repeatedly experience unwanted and distressing thoughts/images (known as obsessions) and engage in repetitive behaviours (known as compulsions) to reduce their anxiety, which leads to significant distress. Individuals with OCD rarely get better on their own, indicating the need for effective treatments. The cognitive model of OCD suggests that intrusive thoughts are common to everyone, but in OCD they are appraised as highly threatening and personally significant. Individuals with OCD tend to overestimate responsibility for preventing harm, leading to intense anxiety. Compulsive behaviours are used to neutralise perceived danger and responsibility, but these safety-seeking behaviours prevent learning that the feared outcome would not occur, thereby maintaining OCD symptoms. NICE Guidelines recommend cognitive behavioural therapy (CBT) as the first-line treatment for OCD. Numerous research papers support the use of CBT, with clinical studies indicating that CBT is more effective than no intervention (waitlist control) and drug interventions. Despite the availability of effective treatments, symptoms often go untreated for several years, with only a minority of obsessional patients receiving appropriate CBT. National Health Service Talking Therapies (NHSTT) services (formerly known as Improving Access to Psychological Therapies (IAPT)) were developed to address health inequalities and increase access to evidence-based psychological interventions in line with NICE recommendations. Through a stepped-care model, patients with ‘mild to moderate’ OCD symptoms are initially offered with Step Two (low-intensity) interventions (computerised (c)CBT) or guided self-help (GSH), while patients with ‘severe’ OCD are offered Step Three (high-intensity) interventions. NHSTT services currently report reliable improvement rates of 53%, with recovery rates likely to be around 30%, which is significantly lower than those reported clinical studies. This study aims to improve OCD recovery rates by training Psychological Wellbeing Practitioners (PWPs) in two NHSTT services to deliver a new low-intensity intervention for OCD, termed ‘focused CBT’. The focused CBT sessions are supported by workbook modules, with treatment involving the development of a shared understanding of their OCD difficulties and the introduction of cognitive and behavioural strategies aimed at addressing factors maintaining OCD symptoms. The secondary aim of the study is to compare groups on general mental health outcomes (anxiety, depression, and general functioning). Who can participate? Qualified psychological wellbeing practitioners (PWPs) working at the two participating NHSTT services. Adult patients aged 18 years and over with OCD as their main problem accepted in two NHSTT services. What does the study involve? Invites for participation will be sent to the PWPs from the service leads. Therapists will express their interest in the trial and provide informed consent via an online form before being randomly allocated (by chance) to deliver either treatment as usual (TAU) or focused CBT. Those in the focused CBT condition will receive training on how to deliver this treatment. Patient referrals to the services will be assessed using their standard triage and assessment procedures, where a main problem description is identified by the assessing clinician. Participants (people with OCD as their main difficulty) will be allocated to a treatment condition randomly (by chance) and have treatment sessions with PWPs. Random allocation will be completed on a 1:1 ratio in blocks of four using an online system such as Sealed Envelope. What are the possible benefits and risks of participating? The present study may help to improve OCD recovery rates in local NHSTT and psychological treatment for OCD. This could significantly impact the lives of patients accessing NHSTT for OCD.The present trial is not anticipated to cause any harm, with all participants receiving an active intervention (focused CBT or TAU). Services will manage risk (e.g. safeguarding and self-harm concerns) according to standard NHS talking therapy policies. In line with routine clinical care, clinical treatment notes will be recorded on participants’ electronic NHS care records, and consent forms will be uploaded. Where is the study run from? This study is being conducted at two NHS Talking Therapy services. When is the study starting and how long is it expected to run for? June 2026 to September 2027. Who is funding the study? Oxford NIHR Biomedical Research Centre, UK. Who is the main contact? 1. Roberta McGuinness, roberta.mcguinness@newc.ox.ac.uk 2. Professor Paul Salkovskis, paul.salkovskis@hmc.ox.ac.uk 3. Dr Saarim Aslam, saarim.aslam@psy.ox.ac.uk Severity of OCD symptoms the Obsessive Compulsive Inventory (OCI) assessment and every intervention session Severity of depression symptoms the Patient Health Questionnaire (PHQ-9) assessment and every intervention session Severity of anxiety symptoms the Generalised Anxiety Disorder (GAD-7) Questionnaire assessment and every intervention session General functioning the Work and Social Adjustment Scale (WSAS) assessment and every intervention session Ethics approval required London - Riverside Research Ethics Committee

2 Redman Place, Stratford

London United Kingdom E20 1JQ 26/LO/0107 10.1186/ISRCTN74790966 357922 357922 Interventional Randomized controlled trial Open (masking not used) Active Parallel Treatment Not applicable 2027-09-27T00:00:00.000Z United Kingdom England Oxford Health NHS Foundation Trust

Littlemore Mental Health Centre Sandford Road Littlemore

Oxford England OX4 4XN false 1. Aged 18+ 2. Any gender 3. Problem descriptor of OCD both at triage and confirmed at first assessment with their therapist 4. Clinical level OCD symptoms on OCI total and/or subscales 5. Sufficient understanding of English to complete questionnaires and workbooks Mixed 18 Years 120 Years All 68 0 Pre-enrolment exclusion criteria as set by services will be the following: 1. Lack of capacity to consent 2. Alcohol or substance misuse that would impact therapy and which the individual is unwilling to reduce Trial exclusion criteria will be: 1. Acute suicide or safeguarding risk that cannot be managed 2. Current enrolment in another research study 3. Introduction or altered dose of antidepressant or anti-anxiety medication within the past month 4. Presence of a long-term health condition as their main problem 5. Inability to access study materials (e.g. no access to the internet) 2026-06-01T00:00:00.000Z 2027-06-27T00:00:00.000Z Patients with a primary problem descriptor of obsessive compulsive disorder as identified at triage and confirmed at first assessment with therapist. Mental and Behavioural Disorders The present randomised control trial aims to compare the efficacy of focused CBT with treatment as usual for OCD at two NHS Talking Therapy services . Focused CBT draws on the methodology outlined by Clark et al. (1999), Aslam et al. (2025), and Johnsen et al. (2025). Focused CBT sessions are supported by workbook modules, with treatment involving the development of a shared understanding of patients' OCD difficulties and the introduction of cognitive and behavioural strategies aimed at addressing factors maintaining OCD symptoms. Treatment will involve six to eight 30-minute sessions delivered online or face-to-face by psychological wellbeing practitioners. Treatment as usual at the services includes Guided Self-Help (GSH) and/or computerised CBT (cCBT). Interventions at both services can be delivered via phone, face-to-face, or MS Teams, depending on the individual’s preference. Both GSH and cCBT are classified as low- intensity, Step Two interventions. GSH involves a treatment planning session lasting up to 45 minutes, followed by six to eight 30-minute sessions with a PWP. Self-help materials are provided between sessions, with treatment focusing on psychoeducation and cognitive and behavioural skills. Meanwhile, cCBT is an online intervention delivered via the ‘SilverCloud’ platform. An initial ‘set-up’ call, lasting up to 20 minutes, is offered to explain the OCD programme. Patients then access the programme online, working through modules independently. Throughout the programme, patients are offered up to six online reviews, lasting up to 15 minutes each. Patients will be randomly allocated (using sampling without replacement) to either the intervention (focused CBT) or TAU (cCBT or GSH) condition on a 1:1 ratio in blocks of four using an online system called ‘Sealed Envelope’. A central randomisation system will be used to ensure allocation concealment, with an independent member of the research team not involved in the consent process, assigning participants to their treatment conditions. Clinical teams will be informed of the participant’s intervention condition, with services assigning therapists randomised to the condition. It will not be possible to blind therapists or participants to the intervention. Behavioural Not expected to be made available 3b8a317d-6c2d-490b-a9e0-757c3a77ae90 deda7b5b-b516-4d55-b5f4-b35601dad4fa daa73349-03f4-4d3e-889d-adc07f698a5c 5f74323f-d143-43d4-9939-00f059046972 79b3d64c-73dc-4a4b-932b-8de1e3f990af No Roberta McGuinness Principal investigator

Isis Education Centre, Warneford Hospital, Headington

Oxford United Kingdom OX3 7JX +44 (0)7919886360 roberta.mcguinness@newc.ox.ac.uk Public Saarim Aslam Scientific Public

Isis Education Centre, Warneford Hospital, Headington

Oxford United Kingdom OX3 7JX +44 (0)7919819678 saarim.aslam@oxfordhealth.nhs.uk Public Paul Salkovskis Scientific

Isis Education Centre, Warneford Hospital, Headington

Oxford United Kingdom OX3 7JX +44 (0)1865226369 paul.salkovskis@hmc.ox.ac.uk Public Oxford Health NHS Foundation Trust https://ror.org/04c8bjx39 Non-commercial NIHR Oxford Biomedical Research Centre http://dx.doi.org/10.13039/501100013373 37191564 true A feasibility study of a virtual reality café for people with eating disorders The aim of this study is to establish whether it is feasible to recruit, retain and follow-up participants with eating disorders to receive our newly developed virtual reality (VR) café intervention in addition to their normal treatment. We will also assess the feasibility of collecting outcome data and assess the completeness of these data. We will assess: 1. Recruitment: the number and proportion of patients who are potentially eligible, approached for consent, and consent to participate (routes via which participants were approached or contacted the relevant NHS research team will be documented) 2. Retention: the number and proportion of participants completing the study 3. Demographic, diagnosis and service use data on the individuals we recruit and what other treatment they receive 4. The numbers of sessions of VR completed, and the pattern of use of the VR intervention 5. The acceptability of the intervention, including via qualitative interviews 6. Any adverse experiences in relation to the VR intervention We will collect both qualitative and quantitative data from participants, parents of younger participants, and clinicians, as well as attempting to collect demographic and qualitative data from potential participants who decide not to participate. We will also passively collect eye-tracking data to enable us to have a more detailed understanding of what participants attend to within the VR environment. Background and study aims Eating disorders are serious mental health conditions. Many people with eating disorders find social eating settings, like cafes and restaurants, challenging. This can affect their life and can make recovery more difficult. The aim of this study is to find out whether it is possible to offer a new kind of treatment in the NHS to help people with eating disorders who find places like cafes difficult. The treatment we are inviting people to try out is a virtual reality (VR) café, where people with eating disorders can practise situations they find difficult, like ordering food or interacting with café staff, in a safe and controlled way. The treatment has been developed with people who have current and past experience of eating disorders and clinicians who are experienced in treating eating disorders. We want to find out whether people will take part in a study like this, whether they will stay in the study until it ends, and whether they find the VR café useful. Who can participate? People aged 14-25 years who are currently receiving treatment for any eating disorder in one of two participating NHS trusts can participate What does the study involve? The study involves attending up to six 1-hour sessions using the VR café, with support from a trained clinician. People who take part will attend these sessions as well as carrying on with their usual treatment for their eating disorder. VR café sessions will take place where participants usually see their eating disorder team or at their NHS mental health trust’s research base. We’ll collect information about how many people agree to take part, how many people complete the VR sessions, and how useful people find the VR café. Participants will be asked to complete some questionnaires before they start VR sessions, at the end of their first VR session, 6 weeks after their first VR session, and 3 months after their first VR session. We’ll also collect information about how people engage with the VR environments, and some types of information from health records to help us understand which people try out the VR café. To find out more about people’s experiences of participating, we’ll interview some of the young people who try out the VR café, some of their parents/carers, and some of the clinicians who support people using the treatment. We’ll also interview some of the people who didn’t want to take part in the study to understand why this might be. What are the possible benefits and risks of participating? As this is the first time the VR café has been used in the NHS, we don’t know whether everybody will benefit, but participants may find the treatment helpful for practising challenges related to going into and ordering food and drink in social eating environments such as cafés. Some people can experience motion sickness while using a VR headset. We believe that this risk is very small because participants will be seated while using the VR café. Some participants might also find reflecting on their experience of having an eating disorder distressing or find trying out the treatment challenging. Clinicians will support participants at all times during their use of the VR café, and participants can choose to take off the VR headset or stop VR café sessions altogether at any time. Where is the study run from? University of Bristol (UK) When is the study starting and how long is it expected to run for? June 2026 to October 2027 Who is funding the study? National Institute for Health and Care Research (NIHR) (UK) Who is the main contact? Dr Helen Bould, Helen.Bould@bristol.ac.uk Feasibility of recruitment and retention will be measured by assessing the number of potentially eligible patients in the clinical settings during the study period, the number of patients approached to participate via each recruitment route during the study period, the number of participants consenting to participate during the study period, the number of potential participants declining to participate (and reasons given) during the study period, and the number of participants who consent to participate who remain in the trial at 3-month follow-up. The Feasibility of Assessment Battery will be measured by assessing the number of participants completing all measures at baseline and the number of participants completing all measures at the end of session 1 and at 6-week and 3-month follow-ups. Feasibility of the intervention will be measured by: 1. Documenting which clinician delivers the intervention (patient’s own clinician or a member of the NHS research team with experience of working in mental health) during the study period 2. Assessing VR engagement metrics, including: 2.1. Participant goal-setting re which scenarios they want to try and how many times they want to try it, captured at the end of the study period 2.2. Number (and which) VR sessions are completed, captured at the end of the study period 2.3. Time spent using VR, captured at the end of the study period 2.4. How often scenarios are repeated, captured at the end of the study period 2.5. Whether participants and clinicians think further sessions would have been useful for each participant, captured at the end of the study period Fidelity to the treatment will be measured by asking both the participant and the clinician to complete a brief measure, documenting whether they (1) set goals in relation to the VR scenario they would try, (2) tried one or more VR scenarios, and (3) discussed the experience of completing the scenario and reviewed their goals, completed at the end of each VR session. 1. Acceptability of the VR intervention to participants, through the proxy measures above, as well as by questions on satisfaction, perceived burden, ease of use and likelihood of recommending to others, collected 6 weeks after the first VR session. 2. Any adverse reactions to VR (e.g., motion sickness; stopping a session due to distress), collected during the study period. Questionnaire measures: 1. Anxiety and avoidance in relation to cafes will be measured using a bespoke questionnaire at baseline, end of VR session 1, 6 weeks after the first session, and at the 3-month follow-up 2. Self-efficacy in relation to cafes will be measured using a bespoke questionnaire at baseline, end of VR session 1, 6 weeks after the first session, and at the 3-month follow-up 3. Behaviours in relation to visiting cafés will be measured using a bespoke questionnaire at baseline, end of VR session 1, 6 weeks after the first session, and at the 3-month follow-up 4. Eating disorder symptoms will be measured by the Eating Disorder Examination Questionnaire (EDEQ) at baseline, 6 weeks after the first session, and at the 3-month follow-up 5. Symptoms of Avoidant/Restrictive Food Intake Disorder (ARFID) will be measured by the Short ARFID questionnaire at baseline, 6 weeks after the first session, and at the 3-month follow-up 6. Impact of having an eating disorder on life will be measured by the Clinical Impairment Assessment (CIA) at baseline, 6 weeks after the first session, and at the 3-month follow-up 7. General anxiety will be measured by the General Anxiety Disorder-7 (GAD-7) (18-25 year olds) or Revised Children’s Anxiety and Depression Scale (RCADS) (14-17 year olds) at baseline, 6 weeks after the first session, and at the 3-month follow-up 8. Depression will be measured by the Patient Health Questionnaire-9 (PHQ-9) (18-25 year olds) or Revised Children’s Anxiety and Depression Scale (RCADS) (14-17 year olds) at baseline, 6 weeks after the first session, and at the 3-month follow-up 9. VR side effects will be measured by the Simulator Sickness Questionnaire (SSQ) at baseline and at the end of each VR session 10. Sense of presence/place illusion will be measured at the end of the first VR session Service use measures: Service use measures will be gathered from electronic health records encompassing the study period until the 3-month follow-up: 1. Recorded diagnosis, comorbidities and prescribed medication 2. Nature of “treatment as usual” being received 3. Number and timing of clinical contacts within the eating disorders team, by professional group, before and after consenting to study participation 4. Number and timing of clinical contacts within the mental health trust, by professional group before and after consenting to study participation 5. BMI/% weight for height at the point of (1) starting treatment, (2) joining the study and (3) at 3-month follow-up (to help inform whether, for those for whom weight restoration is part of treatment, there is an optimum time during weight restoration to engage in this treatment) 6. Number of GP contacts during study participation 7. Number of contacts with other health professionals during study participation 8. Number of A&E contacts during study participation 9. Duration of admission [for inpatients] before and after consenting to study participation 10. Legal status of admission [for inpatients] before and after consenting to study participation VR headset measures: 1. Head, hand and eye-tracking data will be collected via VR headsets in all VR sessions during the study period Qualitative data collection: 1. Qualitative interviews will be conducted with a subset of trial participants, decliners, parents/carers, and clinicians during the study period Ethics approval required West of Scotland REC 5

West of Scotland Research Ethics Service Level 2, Administration Building Gartnavel Royal Hospital 1055 Great Western Road

Glasgow United Kingdom G12 0XH 25/WS/0200 10.1186/ISRCTN37191564 362410 CPMS: 70226, NIHR: 302271 362410 70226 302271 Non-randomized study Interventional Non randomised study Treatment 2027-10-30T00:00:00.000Z United Kingdom England Gloucestershire Health and Care NHS Foundation Trust

Edward Jenner Court 1010 Pioneer Avenue Gloucester Business Park

Gloucester England GL3 4AW RTQ@2.16.840.1.113883.2.1.3.2.4.18.48 Oxford Health NHS Foundation Trust

Littlemore Mental Health Centre Sandford Road Littlemore

Oxford England OX4 4XN RNU@2.16.840.1.113883.2.1.3.2.4.18.48 false 1. Aged 14-25 years, with any eating disorder 2. Find social eating challenging 3. Currently accessing treatment for an eating disorder in a participating NHS mental health service 4. People aged 16 years or older who consent to participate 5. People aged 14-15 years old who assent to participate and for whom someone with parental responsibility consents to their participation. Mixed 14 Years 25 Years All 30 0 1. People who lack capacity to consent to participate as assessed during the consent process 2. People who are not able to travel to VR Cafe sessions 3. People who are not fluent in spoken English 4. Members of the project Patient and Public Involvement (PPI) group 2026-06-01T00:00:00.000Z 2027-05-29T00:00:00.000Z Eating disorders Mental and Behavioural Disorders The VR intervention will involve sessions of up to 1 hour in length, in which the participant will use the VR café scenarios with support from the clinician. The clinician will work with the participant to plan, support and debrief from the VR café intervention. The intervention can be delivered either by the participant’s own clinician within the Eating Disorder team (if they have been trained to do so) or by a member of the relevant NHS research team with experience of working in mental health, according to clinician availability and participant preference. Behavioural The datasets generated during and/or analysed during the current study will be stored in a publicly available repository (https://data.bris.ac.uk/data). Anonymised VR usage data, questionnaire data, and qualitative data will be made available (restricted access) to bona fide researchers on request. The data will become available after the study ends, data analysis is complete, and reports have been written. Participants’ consent will be obtained for data sharing and all shared data will be anonymised. Stored in publicly available repository Protocol

4f74db27-c62b-4b23-a22f-a61426f1d7c5 4d427d67-4dfd-42c9-a07b-777642aba698 dca05b50-9a7d-44c4-8210-f723553e751a a4ed2e15-34db-45c5-a099-fd4e8098dc15 81cf8ed2-8f31-4415-a620-8bf9ff680aa3 Yes Protocol file 49310_PROTOCOL_V1.1_07Jan2026.pdf 1ea02766-37a8-4430-bd5b-ff239b4a2403 true application/pdf 1259052 e9919400e0d5897d7fadb3f2c45661fb Laura Chapman Public

Bristol Medical School University of Bristol Canynge Hall 39 Whatley Road

Bristol United Kingdom BS8 2PS - laura.chapman@bristol.ac.uk Public Helen Bould https://orcid.org/0000-0001-8163-3210 Principal investigator Scientific

Bristol Medical School University of Bristol Canynge Hall 39 Whatley Road

Bristol United Kingdom BS8 2PS +44 (0)1174553864 Helen.Bould@bristol.ac.uk Public Laura Chapman Public

Bristol Medical School University of Bristol Canynge Hall 39 Whatley Road

Bristol United Kingdom BS8 2PS - vr-eatingdisorders-project@bristol.ac.uk Public University of Bristol Hospital/treatment centre https://ror.org/0524sp257 Non-commercial National Institute for Health and Care Research http://dx.doi.org/10.13039/501100000272 43471225 true Improving talking therapies treatment of panic disorder: a randomised parallel trial 1. Can we replicate previous study findings with a new, larger sample? That is, a difference in the clinical outcome of panic severity between individuals with panic disorder who receive focused CBT compared to those who receive Step Two Treatment As Usual (TAU). 2. Is there a difference in the clinical outcomes of depression, anxiety and one’s daily functioning between individuals with panic disorder who receive focused CBT compared to those who receive Step Two Treatment As Usual (TAU) on a larger scale? 3. Does agoraphobic avoidance and panic cognitions improve in line with panic outcomes and do they predict outcomes in panic severity? Background and study aims Panic disorder is often treated in NHS talking therapies services by psychological well-being practitioners (PWPs) at Step Two, also known as 'low intensity'. There is a need to improve recovery rates for panic disorder nationally in NHS talking therapies services. A previous pre-registered trial the authors conducted (now published) found a more specific psychological treatment for panic disorder (known as Focused CBT) was more effective than the current treatment as usual for panic disorder in NHS Talking Therapies services. Therefore, this study is being conducted to build on the previous research to examine if these same effects can be observed on a larger scale. The research also aims to examine if focused CBT can result in further improvements on panic and agoraphobic specific measures including fearful panic thoughts and agoraphobic avoidance. Who can participate? Individuals who are 18+ years of age, of any sex and where panic disorder with or without agoraphobia is the main problem. What does the study involve? People with panic disorder at the NHS talking therapies service are asked if they would like to take part in the study. If so, they will be randomly placed (determined by chance) into either the 'focused CBT' treatment or the current treatment provided for panic disorder at the NHS talking therapies services. Participants will then receive the treatment they have been randomly allocated to. The symptoms and severity of the participant's panic, depression, anxiety and the participant's daily functioning are measured before they start treatment, during each treatment session and at the end of treatment. Panic fearful thoughts and agoraphobic avoidance are measured before treatment begins, mid-way through treatment and at the end of treatment. What are the possible benefits and risks of participating? Taking part could help improve the current psychological treatment for panic disorder with or without agoraphobia. It could also help with wider implementation of this focused CBT if deemed more effective. In addition, it would also mean participants will obtain psychological treatment for panic disorder with or without agoraphobia which may help with their difficulties with panic. The research team do not anticipate any risk associated with taking part. Where is the study run from? Oxford Health NHS Foundation Trust (UK) When is the study starting and how long is it expected to run for? February 2026 - December 2027 Who is funding the study? Biomedical Research Centre NIHR - Oxford Health NHS Foundation Trust (UK) Who is the main contact? 1. Dr Saarim Aslam, saarim.aslam@psy.ox.ac.uk 2. Professor Paul Salkovskis, paul.salkovskis@hmc.ox.ac.uk Panic symptom severity Panic Disorder Severity Scale (PDSS) pre treatment, at each treatment session and end of treatment. Depression PHQ-9 pre treatment, at each treatment session and end of treatment Anxiety GAD-7 pre treatment, at each treatment session and end of treatment Work and social adjustment scale Work and Social Adjustment Scale (WSAS) pre treatment, at each treatment session and end of treatment Agoraphobia Modified Agoraphobic Cognitions Questionnaire pre, mid and end of treatment Mobility Mobility Inventory pre, mid and end of treatment Ethics approval required South West - Cornwall & Plymouth Research Ethics Committee

2 Redman Place Stratford

London United Kingdom E20 1JQ 25/SW/0156 10.1186/ISRCTN43471225 363155 363155 Interventional Randomized controlled trial Open (masking not used) Active Parallel Treatment Not applicable 2027-12-31T00:00:00.000Z United Kingdom England Oxford Health NHS Foundation Trust

Littlemore Mental Health Centre Sandford Road Littlemore

Oxford England OX4 4XN RNU@2.16.840.1.113883.2.1.3.2.4.18.48 false 1. Age 18+ 2. English speaking and able to complete questionnaires and workbooks in English 3. Any gender 4. The presence of recurrent panic attacks whereby some are unexpected 5. Panic disorder with or without agoraphobia is the main problem as identified in the problem descriptor Mixed 18 Years 110 Years All 94 0 1. Panic is not the primary difficulty 2. Individual does not have capacity to consent 3.Those with long term physical health conditions 4. Those who are involved in another research project 5. Risk/safeguarding cannot be managed 6. Substance/alcohol use that would impact on therapy and individual unwilling to work to reduce this use 7. Inability to access materials, for example, technology barriers 2026-02-20T00:00:00.000Z 2027-08-31T00:00:00.000Z Panic disorder with or without agoraphobia Mental and Behavioural Disorders 1. Focused CBT: This will involve six-eight sessions, delivered by Qualified Psychological Wellbeing Practitioners (PWPs). Participants randomly allocated to this treatment will receive workbook modules to complete which will introduce each session's topic. They will be required to complete the workbook modules before each session as these workbooks will be used by the PWPs with the participants during the treatment sessions. The workbook modules and treatment sessions will use cognitive behavioural therapy (CBT) techniques tailored to panic disorder to help participants with their panic symptoms. 2. Treatment as usual has two different treatments which are currently provided by the NHS Talking Therapies Services taking part. These are (i) Guided Self Help (GSH) and (ii) computerised CBT (cCBT). GSH involves a consultation with a PWP followed by six-eight treatment sessions whereby the participant will be guided through different skills and techniques to help with the panic symptoms and difficulties. They are also given workbooks to complete prior to the sessions. cCBT is delivered on an online platform which involves seven modules teaching participants skills to help with their panic symptoms and involves online reviews by a PWP. Random allocation: Participants will be randomly allocated to either focused CBT or treatment as usual. Randomisation is being stratified by site and using blocked randomisation. The tool used will be an online randomisation tool such as ‘Sealed Envelope’. If participants are randomly allocated to treatment as usual, they will follow normal NHS Talking Therapies service procedures for allocation to either cCBT or GSH which involves a discussion of these options with the participant and an agreement between the participant and clinician of which is the most suitable option for them. This is the normal procedure for TAU in these services. Administration: Focused CBT is administered face-to-face or online via MS Teams. Both cCBT and GSH are administered either face to face, online via MS Teams or by telephone. This is based on participant preference and clinical need. Duration: Focused CBT intervention is a total of 6-8 weeks which is dependent upon the individual's panic presentation. Treatment as usual which is both Guided Self Help and Computerised CBT is also for 6-8 weeks. There is no follow up for this study. Behavioural Not expected to be made available 8b698d3e-349e-4fc1-a9b9-a404d756191e 9aa72daa-f64c-455b-8a80-bf45a7706d41 ebf30a83-dffa-403b-92c3-43e0f33f09c2 8ea2387c-3608-412b-b152-73c6d77c6bde No Saarim Aslam https://orcid.org/0000-0001-7488-904X Public Scientific Principal investigator

University of Oxford, Department of Experimental Psychology Oxford Health NHS Foundation Trust Isis Education Centre Warneford Hospital

Oxford United Kingdom OX3 7JX +44 (0)7919819678 saarim.aslam@psy.ox.ac.uk Public Paul Salkovskis https://orcid.org/0000-0002-2951-2283 Public Scientific

The Oxford Institute of Clinical Psychology Training and Research University of Oxford, Department of Experimental Psychology Oxford Health NHS Foundation Trust Isis Education Centre Warneford Hospital

Oxford United Kingdom OX3 7JX +44 (0)1865 226 369 paul.salkovskis@hmc.ox.ac.uk Public Oxford Health NHS Foundation Trust https://ror.org/04c8bjx39 Non-commercial NIHR Oxford Biomedical Research Centre http://dx.doi.org/10.13039/501100013373 23087950 true Systematic Assessment of the Medical Utility of Radiology Artificial Intelligence (SAMURAI) in Fracture Detection SAMURAI-Fracture Primary Objective: To evaluate whether implementation of an AI fracture detection tool reduces the proportion of patients having unnecessary NHS healthcare contacts as a result of incorrect diagnoses, i.e. false positive/negative conclusions. Secondary Objectives: To assess the technical performance of an AI fracture detection tool, and its impact on clinician experience, overall patient care experience and service provision. Background and study aims Broken bones (fractures) are commonly misdiagnosed in emergency departments, which can lead to patients experiencing delayed recovery, prolonged pain, and unnecessary follow-up visits to the NHS. In the UK, around 3.7 to 8.7% of suspected fractures are misdiagnosed, primarily because busy emergency staff incorrectly interpret X-rays. This can also lead to patients without fractures being incorrectly told they have a broken bone, resulting in unnecessary treatments. This study aims to test whether using artificial intelligence (AI) software to help clinicians identify fractures on X-rays can reduce these diagnostic errors and improve patient care. The AI tool automatically analyses X-ray images and highlights areas where fractures might be present, helping doctors and nurses make more accurate diagnoses. Who can participate? Anyone aged 2 years or older who attends an emergency department or minor injuries unit and has an X-ray taken for a suspected fracture can be included in this study. This includes both children and adults. Patients cannot participate if they are under 2 years old, need X-rays for suspected child abuse, or require imaging of the skull, facial bones, teeth, or neck spine. Children under 18 with suspected lower back fractures are also excluded. Patients can opt out by using the national NHS data opt-out system or by completing an opt-out form displayed in the emergency department. What does the study involve? The study will run across several NHS hospitals and minor injuries units in the Thames Valley region. During the 6-month study period, AI software will be installed at each site. The AI tool will alternate between being switched on and off each month, so doctors sometimes have access to the AI assistance and sometimes do not. Most patients will simply receive their normal emergency care. The study team will collect information from medical records to see whether the AI reduces misdiagnoses and unnecessary follow-up appointments. No additional X-rays or tests are needed. A small number of patients (30 at each hospital) will be asked if they are willing to be contacted one month after their visit to complete a short questionnaire about their experience. Staff at participating hospitals will also be invited to complete questionnaires about their experience using the AI tool. What are the possible benefits and risks of participating? The AI tool may help clinicians detect fractures more accurately, which could mean patients receive the right treatment more quickly and have fewer unnecessary follow-up visits. Patients might also experience less pain and recover more quickly if their fracture is correctly identified early on. For patients without fractures, there may be less chance of being incorrectly diagnosed and receiving unnecessary treatment. The study involves minimal risk to patients. The AI software is a support tool only and does not replace the doctor's judgement. Clinicians will still make the final decision about diagnosis and treatment. The main risk is that the AI might occasionally make errors, but the study team will carefully monitor the tool's performance to ensure it is working safely. There are no physical risks as patients receive standard care with no additional procedures. Where is the study run from? The study is run from Oxford University Hospitals NHS Foundation Trust, with the main coordination happening at Headley Way, Oxford OX3 9DU. The study will take place across four hospital trusts in the Thames Valley region: 1. Oxford University Hospitals (John Radcliffe Hospital and Horton General Hospital emergency departments) 2. Oxford Health NHS Foundation Trust (minor injuries units) 3. Royal Berkshire NHS Foundation Trust (Royal Berkshire Hospital emergency department and associated minor injuries units) 4. Buckinghamshire Healthcare NHS Trust (Stoke Mandeville Hospital emergency department and associated minor injuries units) When is the study starting and how long is it expected to run for? The study is expected to start in December 2025 and run until December 2026, lasting approximately 12 months in total. Patient recruitment will take place over a six-month period from December 2025 to July 2026. Who is funding the study? The study is funded by Radiobotics, the company that manufactures the AI fracture detection software being tested. Who is the main contact? Prof. Alex Novak, Alex.Novak@ouh.nhs.uk Unnecessary NHS contacts measured via electronic patient record audit of composite endpoints (phone consultations, repeat ED attendances, additional imaging, GP consultations, late fracture clinic referrals, inappropriate early clinical use, unnecessary imaging, immobilization, and sick leave) compared between periods when AI system is active ("On") versus inactive ("Off") throughout the entire 6-month study period (December 2025 – May 2026), with comparison occurring monthly during the alternating On/Off periods. Patient Impact: 1. False negative fracture detection rate measured by comparison of AI algorithm output versus final radiology report at each X-ray during AI "On" periods (December 2025 – May 2026) 2. False positive fracture detection rate measured by comparison of AI algorithm output versus final radiology report at each X-ray during AI "On" periods (December 2025 – May 2026) 3. Number of inappropriate interventions (unnecessary treatments/referrals) measured via electronic patient record audit comparing AI "On" versus AI "Off" periods throughout the 6-month study period 4. Patient-reported outcomes measured using the EQ-5D questionnaire at 1 month post-initial ED/MIU presentation (December 2025 – May 2026) Clinician Impact: 1. Clinician satisfaction and confidence with the AI tool measured using a 5-point Likert scale questionnaire at baseline (December 2025) and 6 months (May 2026) Service Impact: 1. Number of patients referred to Fracture Clinic from ED/MIU measured via electronic patient record and RIS audit comparing AI "On" versus AI "Off" periods throughout the 6-month study period 2. Number of patients admitted to hospital with suspected fractures measured via electronic patient record audit comparing AI "On" versus AI "Off" periods throughout the 6-month study period 3. Number of patients recalled to ED due to missed fractures (false negatives) measured via electronic patient record audit comparing AI "On" versus AI "Off" periods throughout the 6-month study period 4. Number of unplanned reattendances for the same injury measured via electronic patient record audit comparing AI "On" versus AI "Off" periods throughout the 6-month study period 5. Length of Stay (LoS) in ED/MIU for patients with suspected fractures (measured in minutes from registration to discharge) via electronic patient record audit comparing AI "On" versus AI "Off" periods at each patient visit throughout the 6-month study period Technical Performance: 1. Sensitivity and specificity of the AI algorithm measured by comparison of algorithm output to final radiology report as gold standard at each X-ray during AI "On" periods (December 2025 – May 2026) 2. Sensitivity and specificity by subgroup (anatomical region, fracture type, patient demographics, age, ethnicity, and comorbidities) measured by comparison of algorithm output to final radiology report by subgroup during AI "On" periods (December 2025 – May 2026) 3. Number of X-rays rejected or not processed by the AI algorithm (among those within intended use) measured via comparison of vendor algorithm processing logs versus hospital EPR/RIS imaging requests throughout the AI "On" periods (December 2025 – May 2026) Ethics approval required UK Health Research Authority

2 Redman Place, Stratford

London United Kingdom E20 1JQ 357391 Joint Research Office, Oxford University Hospitals NHS Foundation Trust

Second Floor, OUH Cowley Unipart House Business Centre, Garsington Road

Oxford United Kingdom OX4 2PG PID18979-SI001 South Central – Oxford C Research Ethics Committee

Oxford University Hospitals NHS Foundation Trust Unipart House Business Centre, Garsington Road

Oxford United Kingdom OX4 2PG 25/SC/0252 10.1186/ISRCTN23087950 348658 CPMS: 64480 348658 64480 Prospective cluster randomized cross over trial (ABAB/BABA) Interventional Cluster randomised trial Diagnostic 2026-12-31T00:00:00.000Z United Kingdom England Oxford University Hospitals NHS Foundation Trust

John Radcliffe Hospital Headley Way Headington

Oxford England OX3 9DU RTH@2.16.840.1.113883.2.1.3.2.4.18.48 Oxford Health NHS Foundation Trust

Littlemore Mental Health Centre Sandford Road Littlemore

Oxford England OX4 4XN RNU@2.16.840.1.113883.2.1.3.2.4.18.48 Royal Berkshire NHS Foundation Trust

Royal Berkshire Hospital London Road

Reading England RG1 5AN RHW@2.16.840.1.113883.2.1.3.2.4.18.48 Buckinghamshire Healthcare NHS Trust

Amersham Hospital Whielden Street

Amersham England HP7 0JD RXQ@2.16.840.1.113883.2.1.3.2.4.18.48 Patient All patients undergoing X-Rays in ED or MIU for a suspected fracture will be eligible for inclusion Mixed 2 Years 100 Years All 45000 0 1. Patients under 2 years old 2. Skeletal survey conducted to assess for non-accidental injury 3. Skull, facial bone, dental, and cervical spine X-rays 4. Thoracolumbar spine X-rays in patients under 18 years old 5. Patient has opted out of data sharing on the National Data Opt-Out 6. Patient completes the opt out questionnaire displayed on posters in the waiting room 2026-02-24T00:00:00.000Z 2026-07-30T00:00:00.000Z Patients undergoing X-ray for suspected fracture in the emergency department or minor injuries unit Injury, Occupational Diseases, Poisoning The trial will involve installing a MHRA- and CE-approved AI fracture detection software at each site for 6 months. Clinicians will be able to view AI annotated images to aid in diagnosis when reviewing X-rays for suspected fracture. Sites will be randomly assigned to begin the trial with the AI algorithm either active ("On") or inactive ("Off") during the first month. Thereafter, the algorithm status will alternate each month (“AI On” and “AI Off”) for the remaining 5 months. This crossover design ensures that each site experiences both conditions multiple times, allowing within-site comparisons of outcomes under AI-assisted versus standard practice. This study will be conducted across four sites, divided into three clusters: Cluster 1: Oxford University Hospitals NHS Foundation Trust: John Radcliffe Hospital ED (Level 1 ED) Horton General Hospital ED (Level 1 ED) Oxford Health Trust: MIUs (Level 3 EDs) Cluster 2: Royal Berkshire NHS Foundation Trust: Royal Berkshire Hospital ED (Level 1 ED) Associated MIUs (Level 3 ED) Cluster 3: Buckinghamshire Healthcare NHS Trust: Stoke Mandeville Hospital ED (Level 1 ED) Associated MIUs (Level 3 ED) All patients undergoing an X-ray for suspected fracture will be eligible for the study. Dedicated research teams at each site will extract data from Electronic Patient Records and share the anonymised data with the central trial team for evaluation of primary and secondary outcomes. We will gather feedback from patients and clinical staff through electronic surveys at each site. These sites will allow for sufficient patient heterogeneity (socioeconomic, geographical, population, ethnicity) as per the INCLUDE guidance to ensure that our results are generalisable to the wider UK population. Device Not Applicable RBFracture The datasets generated during and/or analysed during the current study will be available upon request to Prof. Alex Novak, Chief Investigator, alex.novak@ouh.nhs.uk. Type of data to be shared: Anonymised imaging data (X-ray images processed by RBFracture™ algorithm) and associated anonymised demographic, clinical, and outcome metadata Timing of availability: Data will become available upon publication of the primary results manuscript, anticipated within 12 months of study completion Duration of availability: Data will be made available for a minimum of 5 years post-publication Access criteria and sharing mechanism: Access will be restricted to bona fide researchers undertaking research aligned with the study objectives. Requests will be reviewed by the study steering group. Data will be shared via secure transfer mechanisms compliant with UK GDPR and NHS information governance requirements Participants' consent for data sharing: Participants were not explicitly consented to data sharing, however, the use of routine clinical data via EPR/RIS and an opt-out consent model supports secondary use for research aligned with the original study purpose Data anonymisation: All data will be fully anonymised with the removal of identifiable information; re-identification will not be possible Ethical and legal restrictions: Data sharing will comply with UK GDPR, NHS information governance protocols, and ethical approval conditions. No ethical restrictions are anticipated beyond these standard requirements Additional comments: This dataset of ~45,000 fracture cases will support future post-market surveillance, algorithm validation studies, comparative evaluations of fracture-detection AI tools, and health economic analyses. Available on request 2026 Protocol article in https://pubmed.ncbi.nlm.nih.gov/42629153/ (added 25/08/2026) Protocol

33be037d-4f13-43e1-9453-de95088336c4 ad31c802-1b41-4577-bab1-4d7cbb5aaa72 f9aeff56-2a4b-4bbc-9352-2c83c0e3d883 Yes Alex Novak https://orcid.org/0000-0002-5880-8235 Public Scientific Principal investigator

Headley Way Headington

Oxford United Kingdom OX3 9DU +44 (0)1865 231550 Alex.Novak@ouh.nhs.uk Public Oxford University Hospitals NHS Trust Hospital/treatment centre https://ror.org/03h2bh287 Non-commercial Radiobotics 17122014 true REal world internet COgnitiVE theRapy for Social Anxiety Disorder (RECOVER-SAD) RECOVER-SAD Primary objective: To compare the effectiveness of iCT-SAD to treatment as usual (TAU) in reducing self-reported social anxiety Secondary Objectives: 1. To compare iCT-SAD to TAU on the binary outcomes commonly reported by NHS TT services (reliable improvement and reliable recovery) 2. To compare the effectiveness of iCT-SAD to TAU in reducing symptoms of depression and general anxiety, reducing interference with life due to mental health problems, and improving quality of life 3. To compare changes in employment status/ benefits of iCT-SAD to TAU 4. To compare the therapist time needed and cost-effectiveness of iCT-SAD to TAU Process analyses: 1. To compare the credibility, working alliance, acceptability and treatment satisfaction of iCT-SAD to TAU 2. To compare changes in unhelpful cognitions, safety behaviours and avoidance of iCT-SAD to TAU 3. To explore patient and therapist experience with iCT-SAD Background and study aims Social anxiety disorder (SAD) is a common and distressing mental health problem that can persist for many years and hold people back in life. Cognitive therapy based on the Clark & Wells (1995) model helps people recover and rebuild their lives. Clinical trials have shown it is more effective than alternative treatments (Clark et al, 2003, 2006; Ingul, Aune, & Nordahl, 2013; Mörtberg, Clark, Sundin, & Åberg Wistedt, 2007; Stangier, Heidenreich, Peitz, Lauterbach, & Clark, 2003: Stangier, Schramm, Heidenreich, Berger, & Clark, 2011; Leichsenring et al., 2013; Nordahl et al., 2016). However, many people cannot access the treatment due to shortage of therapists or because they are unable to attend clinic-based therapy during working hours. To overcome these problems, the group who developed cognitive therapy for SAD created an internet version. Instead of attending weekly 90-minute therapy sessions in a clinic, patients learn how to overcome their difficulties by working through an engaging and media-rich internet programme they can access from home at any time. A therapist supports them through the programme, but sessions are by video link or phone and much shorter than usual, as people have already learned many of the lessons of therapy from their online study. Preliminary research shows many patients find the internet cognitive therapy acceptable (Clark, et al, 2023). So far, the reported outcomes are at least as good (often better) than those seen with traditionally delivered therapy in NHS services. These promising findings led the National Institute for Care and Clinical Excellence (NICE) to recommend the internet programme for use in the NHS while further data is being collected to unambiguously assess its value NICE (2023a). NHS resources are limited and need to be spent wisely. NICE (2023b) therefore wishes to know how the internet therapy compares with clinic-based treatment when delivered by NHS staff to people with similarly disabling conditions. This randomized controlled trial will answer NICE’s question. People who are seeking treatment for SAD in six NHS Talking Therapy services and are willing to participate will receive internet cognitive therapy or usual NHS treatment. Comparisons between the treatments will look at how many people recover, how their symptoms and quality of life change, the therapist time needed to deliver the treatments, cost-effectiveness, how satisfied patients and therapists are with the internet treatments and how they describe their experience. Who can participate? 1. People with social anxiety disorder who receive treatment at one of the participating NHS Talking Therapies (NHS TT) services and agree to participate in the study 2. About 20 therapists from participating NHS TT services who will deliver the internet-assisted treatment. What does the study involve? Participating patients will be allocated by chance to receive either the iCT-SAD treatment programme supported by a NHS TT therapist or treatment as usual (TAU) with an NHS TT therapist. It also involves completing questionnaires about their symptoms, thoughts, ways of coping, and quality of life at initial assessment and 22, 44 and 66 weeks after allocation (and at the end of treatment if this is later than 22 weeks). They also rate once how credible they find the treatment they receive, and how satisfied they are with the treatment and with working with their therapist. Some will be invited to attend an interview about their experience with iCT-SAD. Participating therapists will be trained to guide and support patients during the iCT-SAD treatment programme. They will then treat patients with social anxiety participating in the trial. At the end of the study they will complete a questionnaire on their experience with delivering the treatment. Some therapists will be invited to attend an interview about their experience with iCT-SAD. What are the possible benefits and risks of participating? All participants will receive a psychological treatment for their social anxiety disorder that has been shown to be effective. The NHS therapists who deliver the treatments have received training and have regular supervision. As with any psychological treatment, it cannot be guaranteed that every participant will benefit. Undertaking treatment for social anxiety disorder can be challenging. Treatment encourages participants to reflect on their difficulties to understand how social anxiety works and supports them in tackling situations that they may have previously avoided. While doing this may temporarily increase distress, facing these challenges is an important step towards overcoming social anxiety disorder. Treatment will be personalised for each patient. Where is the study run from? University of Oxford (UK) When is the study starting and how long is it expected to run for? March 2024 to December 2028 Who is funding the study? National Institute for Health and Care Research (NIHR) (UK). Who is the main contact? Dr Donna Winston, donna.winston@psy.ox.ac.uk 1. Social anxiety symptoms measured with the Social Phobia Inventory (SPIN) completed at baseline, 22 weeks, 44 weeks and 66 weeks post-randomisation, and actual end of treatment if different from 22 weeks. 1. Reliable improvement and reliable recovery as defined in NHS TT manual based on cut-offs on the Social Phobia Inventory (SPIN) and Patient Health Questionnaire (PHQ-9) completed at 22 weeks after randomisation, and actual end of treatment if different from 22 weeks. 2. Depression symptoms measured with the Patient Health Questionnaire PHQ-9 completed at baseline, 22 weeks, 44 weeks and 66 weeks, and actual end of treatment if different from 22 weeks. 3. Anxiety symptoms measured with the Generalised Anxiety Disorder Questionnaire (GAD-7) completed at baseline, 22 weeks, 44 weeks and 66 weeks, and actual end of treatment if different from 22 weeks. 4. Interference with life due to mental health difficulties as measured with the Work and Social Adjustment Scale (WSAS) completed at baseline, 22 weeks, 44 weeks and 66 weeks, and actual end of treatment if different from 22 weeks. 5. Changes in employment and benefits status measured by patient demographics questionnaire at baseline, 22 weeks, 44 weeks and 66 weeks, and actual end of treatment if different from 22 weeks 6. Quality of life measured by the Recovering Quality of Life (ReQoL) at baseline, 22 weeks, 44 weeks and 66 weeks, and actual end of treatment if different from 22 weeks. 7. Therapist time involved in iCT-SAD and TAU as measured by number of sessions and their duration. 8. Cost effectiveness of iCT-SAD and TAU as measured by EuroQol EQ-5D-5L, Client Service Receipt Inventory, and iMTA Productivity Cost Questionnaire completed at baseline, 22 weeks, 44 weeks, 66 weeks, and actual end of treatment if different from 22 weeks. Process measures: 9. Treatment acceptability and patient satisfaction with treatment assessed with the NHS TT Patient Experience Questionnaire (PEQ), Acceptability Scale and interviews with some iCT-SAD patients at the end of treatment. 10. Credibility of treatment measured with the Borkovec and Nau Credibility scale after the second session with therapist. 11. Quality of therapeutic relationship as measured with the Working Alliance Scale completed by patients and therapists after the second session with therapist. 12. Changes in unhelpful cognitions, safety behaviours, and avoidance as measured by the Social Cognitions Questionnaire, Social Behaviour Questionnaire, Social Attitudes Questionnaire-short, Liebowitz Social Anxiety Scale, and Social Summary Scale at baseline, 22 weeks, 44 weeks, 66 weeks, and actual end of treatment if different from 22 weeks. User experience with iCT-SAD: 13. Therapists’ experience with delivering iCT-SAD assessed with the Therapist Experience Questionnaire and, for some, interview at end of study. 14. Patients’ experience assessed through ratings of helpfulness and free comments provided at the end of each module and, for some, interview at end of study. Ethics approval required London Bloomsbury Ethics Committee

85 Tottenham Ct Road

London United Kingdom W1T 4TQ REC ref: 25/LO/0574 10.1186/ISRCTN17122014 352935 CPMS: 67316 352935 67316 Interventional multisite randomized controlled trial Interventional Randomised controlled trial Treatment 2028-12-31T00:00:00.000Z United Kingdom England Oxford Health NHS Foundation Trust

Littlemore Mental Health Centre Sandford Road Littlemore

Oxford United Kingdom OX4 4XN RNU@2.16.840.1.113883.2.1.3.2.4.18.48 Hertfordshire Partnership University NHS Foundation Trust

The Colonnades Beaconsfield Close

Hatfield United Kingdom AL10 8YE RWR@2.16.840.1.113883.2.1.3.2.4.18.48 Greater Manchester Mental Health NHS Foundation Trust

Prestwich Hospital Bury New Road Prestwich

Manchester United Kingdom M25 3BL RXV@2.16.840.1.113883.2.1.3.2.4.18.48 Homerton Healthcare NHS Foundation Trust

Homerton Row

London United Kingdom E9 6SR RQX@2.16.840.1.113883.2.1.3.2.4.18.48 Health professional Patient Patients: 1. Social Anxiety Disorder is the main psychological problem, and the patient's priority to work on in therapy 2. Any gender, aged 18 years or above with no upper age limit. 3. Willingness to be allocated by chance to either iCT-SAD or NHS TT non-digital psychological treatment as usual (TAU) 4. Able to read and write in English 5. Access to the internet at home (or another safe location) and availability of tablet or laptop/computer, access to a mobile phone that can receive text messages Clinicians: 1. High Intensity CBT therapist or Psychological Well-Being practitioner working within a participating NHS TT service 2. Trained in the delivery of iCT-SAD 3. Willing to participate 4. Clinical capacity and managerial approval to participate Adult 18 Years All 240 Patients: 1. Social Anxiety Inventory (SPIN) score below clinical caseness ( < 19) 2. Acute suicide risk 3. Substance dependence Clinicians: 1. No exclusion criteria 2025-11-24T00:00:00.000Z 2027-03-31T00:00:00.000Z Social anxiety disorder Mental and Behavioural Disorders Participants will be allocated by chance using an online randomisation system (SealedEnvelope) to one of two treatments. - Half of the participants will receive a therapist-assisted internet version of cognitive therapy for social anxiety disorder. Cognitive therapy for social anxiety disorder based on the Clark & Wells model (1995) is recommended by NICE (2013) and international treatment guidance. It is usually delivered in one-to-one sessions. A therapist-assisted internet-delivered version (iCT-SAD) has been found to be efficacious and acceptable to patients. Patients are guided through the online treatment programme by a NHS CBT therapist. Patients work through the therapy modules of iCT-SAD on a secure website, as well as completing treatment-related tasks and activities as part of their daily routine. The therapist releases the modules that are relevant to the individual patient and supports them through messages and video or phone calls. Treatment will be usually be delivered over a period of 3 to 5 months. After treatment and discharge from the service, participants will complete follow-up questionnaires at 44 and 66 weeks after randomisation. - The other half of participants will receive treatment as usual in NHS Talking Therapies services, which usually involves one-to-one video or in-person sessions of an evidence-based psychological treatment for social anxiety disorder with a NHS CBT therapist. Treatment will be usually be delivered over a period of 3 to 5 months. After treatment and discharge from the service, participants will complete follow-up questionnaires at 44 and 66 weeks after randomisation. Behavioural The data sharing plans for the current study are unknown and will be made available at a later date Data sharing statement to be made available at a later date 8f7582b6-64f2-4eda-8fa7-85d29d0843c2 910c64ae-e81f-42b8-8a91-fe02591aeaf8 06a34647-b098-488f-b267-8699625d1d4d de2be7fb-feea-419e-b96b-4e98f17ecf93 No Donna Winston https://orcid.org/0000-0001-6517-6240 Public

Oxford Centre for Anxiety Disorders and Trauma (OxCADAT) Department of Experimental Psychology University of Oxford Life and Mind Building South Parks Rd

Oxford United Kingdom OX1 3EL +44 1865281382 donna.winston@psy.ox.ac.uk Public Anke Ehlers https://orcid.org/0000-0002-8742-0192 Scientific Principal investigator

Oxford Centre for Anxiety Disorders and Trauma (OxCADAT) Department of Experimental Psychology University of Oxford Life and Mind Building South Parks Rd

Oxford United Kingdom OX1 3EL +44 (0)1865618600 anke.ehlers@psy.ox.ac.uk Public University of Oxford University/education https://ror.org/052gg0110 Non-commercial National Institute for Health and Care Research http://dx.doi.org/10.13039/501100000272 10554928 true REal world internet COgnitiVE theRapy for PTSD (RECOVER-PTSD) RECOVER-PTSD Primary objective: To compare the effectiveness of digitally enabled cognitive therapy for PTSD (iCT-PTSD) to treatment as usual (TAU) in reducing PTSD symptoms Secondary objectives: 1. To compare iCT-PTSD to TAU on the binary outcomes commonly reported by NHS TT services (reliable improvement and reliable recovery) 2. To compare the effectiveness of iCT-PTSD to TAU in reducing ICD-11 complex PTSD symptoms 3. To compare the effectiveness of iCT-PTSD to TAU in reducing symptoms of depression and general anxiety, reducing interference with life due to mental health problems, and in improving quality of life 4. To compare therapist time needed and cost-effectiveness of iCT-PTSD to TAU. Process analyses: 1. To compare the credibility, working alliance, acceptability and treatment satisfaction of iCT-PTSD to TAU 2. To compare changes in unhelpful cognitions and safety behaviours of iCT-PTSD to TAU 3. To explore patient and therapist experience with iCT-PTSD Background and study aims Posttraumatic Stress Disorder (PTSD) is a common and distressing mental health problem that can develop after extremely stressful events, may persist for many years and hold people back in life. Cognitive therapy based on Ehlers & Clark’s (2000) model of PTSD helps people recover and rebuild their lives. Clinical trials have shown it is very effective and acceptable to patients and more effective than a range of other treatments (Ehlers et al., 2003, 2005, 2014, 2023). However, many people cannot access the treatment due to shortage of therapists or because they are unable to attend clinic-based therapy during working hours. To overcome these problems, the group who developed cognitive therapy for PTSD created an internet version (iCT-PTSD). Instead of attending weekly 90-minute therapy sessions in a clinic, patients learn how to overcome their difficulties by working through an engaging and media-rich internet programme they can access from home (or another safe place) at any time. A therapist supports them through the programme. Sessions are by video link or phone and shorter than usual sessions, as people have already learned many of the lessons of therapy from their online study. Previous research shows that many patients with PTSD find the internet cognitive therapy acceptable (Ehlers et al, 2023). So far, the reported outcomes are at least as good (often better) than those seen with traditionally delivered therapy in NHS services. These promising findings led the National Institute for Clinical and Care Excellence (NICE) to recommend the internet programme for use in the NHS while further data is being collected to unambiguously assess its value (NICE, 2023a). NICE (2023b) wishes to know how the internet therapy compares with clinic-based treatment when delivered by NHS staff to people with similarly disabling PTSD. This randomised controlled clinical trial will answer NICE’s question. People who are seeking treatment for PTSD in NHS Talking Therapies for anxiety and depression services in 4 NHS Trusts in England and are willing to participate will receive internet cognitive therapy (iCT-PTSD) or usual NHS treatment. Comparisons between the treatments will look at how their symptoms and quality of life change, how many people recover, the therapist time needed to deliver the treatments, cost-effectiveness, how satisfied patients and therapists are with the internet treatments and how they describe their experience. Who can participate? 1. People with posttraumatic stress disorder who receive treatment at one of the participating NHS Talking Therapies (NHS TT) services and agree to participate in the study 2. About 20 therapists from participating NHS TT services who will deliver the internet-assisted treatment. What does the study involve? Participating patients will be allocated by chance to receive either either the iCT-PTSD treatment programme supported by a NHS TT therapist or treatment as usual (TAU) with an NHS TT therapist. It also involves completing questionnaires about their symptoms, thoughts, ways of coping, and quality of life at initial assessment and 22, 44 and 66 weeks after allocation (and at the end of treatment if this is later than 22 weeks). They also rate once how credible they find the treatment they receive, and how satisfied they are with the treatment and with working with their therapist. Some will be invited to attend an interview about their experience with iCT-PTSD. Participating therapists will be trained to guide and support patients during the iCT-PTSD treatment programme. They will then treat patients with PTSD participating in the trial. At the end of the study they will complete a questionnaire on their experience with delivering the treatment. Some therapists will be invited to attend an interview about their experience with iCT-PTSD. What are the possible benefits and risks of participating? All participants will receive a psychological treatment for their PTSD that has been shown to be effective. The NHS therapists who deliver the treatments have received training and have regular supervision. As with any psychological treatment, it cannot be guaranteed that every participant will benefit. Undertaking treatment for PTSD can be challenging. Treatment encourages participants to reflect on their difficulties to understand how PTSD works and supports them in tackling situations that they may have previously avoided. While doing this may temporarily increase distress, facing these challenges is an important step towards overcoming PTSD. Treatment will be personalised for each patient. Where is the study run from? University of Oxford (UK) When is the study starting and how long is it expected to run for? March 2024 to December 2028 Who is funding the study? National Institute for Health and Care Research (NIHR) (UK). Who is the main contact? Dr Donna Winston, donna.winston@psy.ox.ac.uk 1. PTSD symptoms measured with the PCL Symptom Checklist for DSM-5 (PCL-5) completed at baseline, 22 weeks, 44 weeks and 66 weeks post-randomisation, and actual end of treatment if different from 22 weeks. 1.. Reliable improvement and reliable recovery as defined in NHS TT manual based on by cut-offs on the PTSD Symptom Checklist for DSM-5 (PCL-5) and Patient Health Questionnaire (PHQ-9) at 22 weeks after randomisation, and actual end of treatment if different from 22 weeks. 2. Complex PTSD symptoms measured with the International Trauma Questionnaire (ITQ) at baseline, 22 weeks, 44 weeks and 66 weeks, and actual end of treatment if different from 22 weeks. 3. Depression symptoms measured with the Patient Health Questionnaire (PHQ-9) completed at baseline, 22 weeks, 44 weeks and 66 weeks, and actual end of treatment if different from 22 weeks, and actual end of treatment if different from 22 weeks. 4. Anxiety symptoms measured with the Generalised Anxiety Disorder Questionnaire (GAD-7) completed at baseline, 22 weeks, 44 weeks, 66 weeks and actual end of treatment if different from 22 weeks. 5. Interference with life due to mental health difficulties as measured with the Work and Social Adjustment Scale (WSAS) completed at baseline, 22 weeks, 44 weeks and 66 weeks, and actual end of treatment if different from 22 weeks.. 6. Changes in employment and benefits status measured by patient demographics questionnaire at baseline, 22 weeks, 44 weeks and 66 weeks, and actual end of treatment if different from 22 weeks. 7. Quality of life measured by the Recovering Quality of Life (ReQoL) at baseline, 22 weeks, 44 weeks and 66 weeks, and actual end of treatment if different from 22 weeks. 8. Therapist time involved in iCT-PTSD and TAU as measured by number of sessions and their duration. 9. Cost effectiveness of iCT-PTSD and TAU as measured by EuroQol EQ-5D-5L, Client Service Receipt Inventory, and iMTA Productivity Cost Questionnaire completed at baseline, 22 weeks, 44 weeks, 66 weeks, and actual end of treatment if different from 22 weeks. Process measures: 10. Treatment acceptability and patient satisfaction with treatment assessed with the NHS TT Patient Experience Questionnaire (PEQ), Acceptability Scale and interviews with some iCT-PTSD patients at the end of treatment. 11. Credibility of treatment measured with the Borkovec and Nau Credibility scale after the second session with therapist. 12. Quality of therapeutic relationship as measured with the Working Alliance Scale completed by patients and therapists after the second session with therapist. 13. Appraisals of the trauma and its aftermath as measured with a short version of the Posttraumatic Cognitions Inventory (PTCIs) given at baseline, 22 weeks, 44 weeks and 66 weeks, and actual end of treatment if different from 22 weeks. 14. Qualities of trauma memories measured with a short version of the trauma memory questionnaire (TMQ) given at baseline, 22 weeks, 44 weeks and 66 weeks, and actual end of treatment if different from 22 weeks. 15. Responses to intrusive memories measured with the Response to Intrusions Questionnaire (RIQ) given at baseline, 22 weeks, 44 weeks and 66 weeks, and actual end of treatment if different from 22 weeks. 16. Safety behaviours measured with the Safety Behaviours Questonnaire (SBQ) given at baseline and at baseline, 22 weeks, 44 weeks and 66 weeks, and actual end of treatment if different from 22 weeks and actual end of treatment if different from 22 week 17. Dissociation measured with a short version of the Trait-State Dissociation Questionnaire (TDSQ) given at baseline at baseline, 22 weeks, 44 weeks and 66 weeks . 18. Patient activity on the online iCT-PTSD programme such as time spent on the programme and modules completed, recorded during treatment User experience with iCT-PTSD: 1. Therapists’ experience with delivering iCT-PTSD assessed with the Therapist Experience Questionnaire and, for some, interview at end of study. 2. Patients’ experience assessed through ratings of helpfulness and free comments provided at the end of each module, and, for some, interview at end of study. Ethics approval required London Bloomsbury Ethics Committee

85 Tottenham Ct Road

London United Kingdom W1T 4TQ 25/LO/0575 10.1186/ISRCTN10554928 354700 CPMS ID 67297 354700 CPMS ID 67297 Interventional multisite randomized controlled trial Interventional Randomised controlled trial Treatment 2028-12-31T00:00:00.000Z United Kingdom England Oxford Health NHS Foundation Trust

Littlemore Mental Health Centre Sandford Road Littlemore

Oxford United Kingdom OX4 4XN RNU@2.16.840.1.113883.2.1.3.2.4.18.48 Hertfordshire Partnership University NHS Foundation Trust

The Colonnades Beaconsfield Close

Hatfield United Kingdom AL10 8YE RWR@2.16.840.1.113883.2.1.3.2.4.18.48 Greater Manchester Mental Health NHS Foundation Trust

Prestwich Hospital Bury New Road Prestwich

Manchester United Kingdom M25 3BL RXV@2.16.840.1.113883.2.1.3.2.4.18.48 Homerton Healthcare NHS Foundation Trust

Homerton Row

London United Kingdom E9 6SR RQX@2.16.840.1.113883.2.1.3.2.4.18.48 Health professional Patient Patients: 1. Post-Traumatic Stress Disorder is the main psychological problem, and the patient's priority to work on in therapy 2. Any gender, aged 18 years or above with no upper age limit 3. Access to an internet-enabled device at home or another safe location with a reliable internet connection; access to a mobile phone that can receive text messages 4. Able to speak, read and write English 5. Willingness to be allocated by chance to either iCT-PTSD or NHS TT non-digital psychological treatment as usual (TAU) Clinicians: 1. High intensity CBT therapist working within a participating NHS TT service 2. Trained in the delivery of iCT-PTSD 3. Willing to participate 4. Clinical capacity and managerial approval to participate Adult 18 Years All 240 Patients: 1. PTSD Checklist 5 (PCL-5) score below clinical caseness (< 32) 2. Acute suicide risk 3. Substance dependence Clinicians: 1. No exclusion criteria 2025-11-24T00:00:00.000Z 2027-03-31T00:00:00.000Z Posttraumatic stress disorder Mental and Behavioural Disorders Participants will be allocated by chance using an online randomisation system (SealedEnvelope) to one of two treatments. - Half of the participants will receive a therapist-assisted internet version of cognitive therapy for PTSD. Cognitive therapy is a trauma-focused cognitive behavioural treatment for PTSD recommended by NICE (2018) and international treatment guidelines. It focuses on core factors maintaining PTSD according to Ehlers and Clark’s (2000) model: Personal meanings of the trauma and its aftermath, disjointed trauma memories and unhelpful cognitive and behavioural coping strategies. It is usually delivered in one-to-one sessions. The therapist-assisted internet delivered version (iCT-PTSD) has been found to be efficacious and acceptable to patients. Patients are guided through the online treatment programme by a NHS CBT therapist. Patients work through the therapy modules on a secure website, as well as completing treatment-related tasks and activities as part of their daily routine. The therapist releases the modules that are relevant to the patient and supports them through messages and weekly video or phone calls. Treatment will be usually be delivered over a period of 3 to 5 months; the duration will depend on the number of traumas that will be addressed in therapy. After treatment and discharge from the service, participants will complete follow-up questionnaires at 44 and 66 weeks after randomisation. - The other half of participants will receive treatment as usual in NHS Talking Therapies services usually involves one-to-one video or in-person sessions of an evidence-based psychological treatment for PTSD with a NHS CBT therapist. Treatment will be usually be delivered over a period of 3 to 5 months; the duration will depend on the number of traumas that will be addressed in therapy. After treatment and discharge from the service, participants will complete follow-up questionnaires at 44 and 66 weeks after randomisation. Behavioural The data sharing plans for the current study are unknown and will be made available at a later date Data sharing statement to be made available at a later date 6fb47899-1a1b-465b-b7c2-a0d92c6cbe96 71b72903-f957-41f6-a53a-a78eaf33f13b d331747c-45e5-49f6-a7a5-acd524f4b16c feaba928-c902-471e-a52c-5d7d18a5426e No Donna Winston Public

Oxford Centre for Anxiety Disorders and Trauma (OxCADAT) Department of Experimental Psychology University of Oxford Life and Mind Building South Parks Rd

Oxford United Kingdom OX1 3EL +44 1865281382 donna.winston@psy.ox.ac.uk Public Anke Ehlers https://orcid.org/0000-0002-8742-0192 Scientific Principal investigator

Oxford Centre for Anxiety Disorders and Trauma (OxCADAT) Department of Experimental Psychology University of Oxford Life and Mind Building South Parks Rd

Oxford United Kingdom OX1 3EL +44 1865618600 anke.ehlers@psy.ox.ac.uk Public University of Oxford University/education https://ror.org/052gg0110 Non-commercial National Institute for Health and Care Research http://dx.doi.org/10.13039/501100000272 86601865 true Developing and testing an intervention for shift work sleep disorder in NHS workers: a feasibility and acceptability study OxBIS As this is a feasibility study, there is no study hypothesis. Background and study aims Shift work can often lead to significant sleep disruption because the work schedule overlaps with the usual time for sleep and can be confusing for our body clock. Significant problems with falling asleep and staying asleep, or excessive sleepiness due to shift work is called shift work sleep disorder (SWD) and this can have a considerable impact on health and well-being. We aim to develop and test an intervention for SWD in shift workers employed in the National Health Service (NHS). This feasibility study will examine whether the intervention can be delivered in a safe and acceptable way. Who can participate? NHS shift workers who meet the study criteria for SWD from local NHS Trusts What does the study involve? Eligibility will be checked in two stages: an online questionnaire followed by a brief interview. Questionnaires on sleep, fatigue, quality of life, mental health and overall health will be collected at baseline (online or telephone). Participants will also be asked to complete a sleep diary and wear an acti-watch (wrist-worn device similar to a Fitbit that measures movement) for 14 consecutive days; and place a mattress sensor under their bed for the entire study period for sleep estimation. They will then receive six fortnightly, one-to-one, online sessions of the behavioural sleep intervention. Each session will last around one hour and will be delivered by a trained research nurse/member of the research team (termed ‘facilitator’). Questionnaires will be collected at the end of the intervention. A small group of participants and facilitators will be interviewed (online or by telephone) about their experience of the intervention and the study. Data on people coming into and staying in the study and their use of the intervention will be recorded. Based on the study results, a decision will be made on whether we can proceed to a larger trial. What are the possible benefits and risks of participating? Benefits: The participants may benefit from improved sleep by taking part in this study. They will also contribute to research, which may help develop better treatments for people experiencing sleep problems because of working shifts. Risks: We will make clear in participant-facing documents that, if a participant is in any way concerned about their health, they should consult with their GP directly. The participant information sheet will also make it clear that study participation will in no way affect usual care. The intervention provided as part of this study is in addition to usual care and therefore participants will be able to access/continue to access support relevant to their health during the study. The intervention proposed for this study is considered low risk and, therefore, the likelihood of serious adverse events is low. Previous similar research on CBT-I and sleep hygiene education has not reported any serious adverse events attributed to treatment. Few potential risks have been identified and steps taken to address these are outlined below: Emotional discomfort: There is a small chance that the participants may find answering questions about their sleep problems and/or health upsetting. If they do not feel comfortable answering such questions, we would discourage them from participating in the study or taking part in the online screening phase. Risk of suicide or acute mental distress: Suicidal ideation with intent or recent suicide attempt is part of the study exclusion criteria and will be assessed at the eligibility phase via interview (stage 2 screening). Should we identify participants with current suicidal ideation with intent (or acute mental distress) we will provide them with standardised information on where to seek support and inform the participant’s GP practice so that appropriate follow-up can take place. Study consent will require participants to agree to the research team contacting their practice if there is concern about their health at any point during the study. Short-term increase in sleepiness: As the intervention targets sleep and sleepiness, it is anticipated that participants will encounter improvements in sleep quality and/or alertness. However, changes to the sleep pattern may engender short-term increases in sleepiness for some participants. All participants will be alerted to this possibility and be provided with advice in relation to managing sleepiness (which is also a target of the intervention) as well as avoiding activities that require a high degree of vigilance, such as driving. If the facilitators believe excessive sleepiness is conferring an increased risk within the participants’ roles, they will recommend that the participants speak with their line managers/occupational health services. Contraindications for phototherapy: During the stage 2 screening, participants will be asked about conditions that may be exacerbated by using phototherapy. This includes, but is not limited to, eye disease, photosensitive migraines, and photosensitive epilepsy. Although not an exclusion criterion, if the participant indicates a contraindication, light goggles will not be sent in the intervention material pack. Regardless, before initiating phototherapy using the goggles in session 2 of the intervention, the facilitators will recheck for conditions that could be exacerbated using phototherapy. If indicated, the participant will be told not to use the light goggles and focus on natural sources of light instead. Acti-watch skin irritation: The acti-watch can occasionally cause localised skin irritation for some participants. If this happens, we will encourage them to stop using the device(s) and contact the research team. If participants have any concerns in relation to the topics raised in the study or if they believe that they require immediate help during the study, we will advise them to contact their general practitioner or visit their local emergency healthcare services. The helpline number of Samaritans will also be provided. Where is the study run from? University of Oxford (UK) When is the study starting and how long is it expected to run for? April 2023 to June 2026 Who is funding the study? This research programme of work on shift work sleep disorder is funded by the National Institute for Health and Care Research (NIHR) as part of their Programme Grants for Applied Research programme (NIHR203667). Who is the main contact? 1. Dr Thava Priya Sugavanam, priya.sugavanam@ocdem.ox.ac.uk 2. Dr Forrest Tin Wai Cheung, forrest.cheung@ndcn.ox.ac.uk Feasibility: 1. Participant recruitment will be measured by the number of participants recruited per month and the total time taken to reach full recruitment at the end of the study 2. Participant retention will be measured by the proportion of participants who complete the end-of-study assessments at the end of the study 3. Intervention engagement will be measured by the proportion of sessions attended by participants at the end of the study 4. Intervention fidelity will be measured by the proportion of the intervention components covered by the facilitators during the delivery of the intervention at the end of the study Acceptability and experiences: 1. Acceptability will be measured by the adapted theoretical framework of acceptability (TFA) questionnaire at post-intervention 2. Adverse events will be measured by the custom adverse events questionnaire at post-intervention 3. Experiences of participants will be explored through semi-structured interviews at the end of the study 4. Experience of facilitators will be explored through semi-structured interviews at the end of the study Process measures: 1. Pre-sleep arousal will be measured by the Pre-Sleep Arousal Scale (PSAS) at baseline and post-intervention 2. Sleep hygiene behaviours will be measured by the Sleep Hygiene Index (SHI) at baseline and post-intervention Indicators of clinical effectiveness: 1. Self-rated insomnia severity will be measured by the Insomnia Severity Index (ISI) at baseline and post-intervention 2. Self-rated sleepiness will be measured by the Epworth Sleepiness Scale (ESS) at baseline and post-intervention 3. Self-rated fatigue will be measured by the Flinders Fatigue Scale (FFS) at baseline and post-intervention 4. Self-rated health-related quality of life (HRQoL) will be measured by the EuroQoL (EQ-5D-5L) plus the sleep bolt-on at baseline and post-intervention 5. Self-reported depression symptoms will be measured by the Patient Health Questionnaire-9 (PHQ-9) at baseline and post-intervention 6. Impairment will be measured by the Work Productivity and Activity Impairment questionnaire (WPAI) at baseline and post-intervention 7. Sleep onset latency (SOL), wake time after sleep onset (WASO), total sleep time (TST), time in bed (TIB), sleep efficiency (SE), and sleep quality (Likert scale) will be obtained from the sleep diaries at baseline and post-intervention 8. Sleep onset latency (SOL), wake-time after sleep onset (WASO), total sleep time (TST), time in bed (TIB), and sleep efficiency (SE) will be obtained from the acti-watches at baseline and post-intervention 9. Measures of time in bed regularity, sleep stability, sleep structure, and sleep continuity will be collected from the under-mattress sensor at baseline and post-intervention Exploratory: 1. The use of services and resources will be measured by the Adapted Client Service Receipt Inventory (CSRI) at post-intervention Old ethics approval format Approved 20/03/2025, Medical Sciences Interdivisional Research Ethics Committee (MS IDREC) (Research Governance, Ethics & Assurance, Research Services, University of Oxford, Boundary Brook House, Churchill Drive, Headington, Oxford, OX3 7GB, UK; Tel: not applicable; ethics@medsci.ox.ac.uk), ref: 961131 10.1186/ISRCTN86601865 350739 CPMS: 67765, NIHR: 203667 350739 67765 203667 Non-randomized; Interventional; Design type: Treatment, Complex Intervention, Other Interventional Non randomised study Treatment 2026-06-30T00:00:00.000Z United Kingdom England Oxford University Hospitals NHS Foundation Trust

John Radcliffe Hospital Headley Way Headington

Oxford England OX3 9DU RTH@2.16.840.1.113883.2.1.3.2.4.18.48 Oxford Health NHS Foundation Trust

Littlemore Mental Health Centre Sandford Road Littlemore

Oxford England OX4 4XN RNU@2.16.840.1.113883.2.1.3.2.4.18.48 Health professional 1. Willing and able to give informed consent for participation in the study 2. Aged 18 years or above 3. Employed by the NHS 4. Meets criteria for SWD according to self-reported items on the shift work disorder index (SWDI) and semi-structured interview: 4.1. Evidence of insomnia and/or sleepiness attributed to shift work 4.2. Evidence of distress or impairment to occupational/social functioning 4.3. Working non-standard hours (defined as shifts that involve working after 6 pm or before 7 am) for a minimum of 1-3 times a week for at least 3 months 5. Has stable internet access Facilitators must be willing and able to give informed consent to participate in the follow-up interviews Mixed 18 Years 70 Years All 35 35 1. Sleep difficulty explained by another co-occurring health condition or other factor (e.g., caring responsibilities) 2. Not currently working (e.g. long-term absence due to illness or paternity/maternity) 3. Currently receiving formal psychological treatment for sleep difficulties from a healthcare professional 4. Untreated co-morbid sleep disorder (e.g., sleep disordered breathing or sleep-related movement disorder). Comorbid sleep disorders are permitted provided they are actively managed. 5. Diagnosis of bipolar disorder or schizophrenia-spectrum disorders 6. Diagnosis of mild cognitive impairment or dementia 7. Current suicidal ideation with intent OR attempted suicide within the past 12 months 8. Currently pregnant or pregnancy planned in the next 5 months 9. Currently receiving cancer treatment 10. Planned major surgery during the next 5 months 11. Unable to understand spoken or written English 12. Taking part in another research study that may affect the outcomes of the present study 13. Unable or unwilling to provide informed consent for the study 14. Unable or unwilling to comply with the study procedures and/or intervention 15. Non-NHS employed staff (e.g., agency staff, students on placement, honorary staff, contractors) There are no specific exclusion criteria for the facilitators to participate in the follow-up interviews. 2025-06-23T00:00:00.000Z 2026-02-04T00:00:00.000Z Shift work sleep disorder Mental and Behavioural Disorders The aim of our study is to develop and test a new behavioural intervention for NHS shift workers who experience sleep problems due to working shifts. This feasibility study will examine whether the intervention is acceptable to participants and will help prepare for a larger trial to assess its impact on sleep and other aspects of health. The study will use a single-arm, mixed-methods feasibility and acceptability design. Up to 30 participants will be recruited from two NHS Trusts in Oxford (Oxford University Hospitals NHS Foundation Trust and Oxford Health NHS Foundation Trust). The study will be promoted to all shift workers in both Trusts through the communication team via existing channels (e.g., weekly staff bulletin, trust social media platforms such as X) and recruitment posters displayed in the staff areas. Eligibility will be assessed in two stages; first through an online screening questionnaire, followed by a brief interview with the research team (for those identified as potentially eligible from stage 1). Baseline assessments (online or over the phone) will be arranged for eligible participants. During this assessment, informed consent will be obtained, and baseline questionnaires will be completed. Following the baseline assessment, participants will be asked to complete a sleep diary and wear an acti-watch for 14 consecutive days, and place a mattress sensor under their bed for the entire study period. The first intervention session will be scheduled following the return of the baseline equipment (sleep diary and acti-watch). There will be six online intervention sessions with approximately one session every two weeks, depending on the participant’s shift schedule. The duration of each session will be approximately one hour. The intervention will be delivered by trained NIHR Research Delivery Network (RDN) nurses, Research Nurses or a member of the research team (termed ‘facilitator’). At the end of the intervention, the research team will contact the participant to complete the post-intervention outcome measures (online or over the phone), including 14-day sleep diary and an acti-watch. Semi-structured interviews on the experience of the intervention and the study procedures will be conducted by one of the researchers with purposively selected participants (n = 15) following completion of the post-intervention assessment. Interviews will last for approximately 45 to 60 minutes and will be audio recorded. Similar semi-structured interviews on the experience of delivering the intervention will be conducted with the facilitators (n = approximately 5) at the end of the study by one of the researchers. The study will be using an online survey provider that is recognised as UK General Data Protection Regulation (UK GDPR) secure for the screening questionnaire and for the collection of outcome measures at baseline and post-intervention (REDCap or Qualtrics). Behavioural Data sharing statement to be made available at a later date

df420539-4602-43ab-970b-f2fd8775eb6c 029b0f45-170d-4907-93ab-66acbc20aa2f 649cf231-8d0c-4f89-879c-35b9d8ee976c 30962d07-7261-49f1-aab6-be52d4dcf756 No Participant information sheet 47462_PIS_V2.0_17Apr25.pdf 6251d494-8d7c-4b8e-a220-bfe4ca093d04 true application/pdf 343709 a0cebac28ba69549f0af07803b4c7419 Thava Priya Sugavanam https://orcid.org/0000-0002-3033-2028 Scientific

Oxford Centre for Diabetes, Endocrinology, and Metabolism (OCDEM) University of Oxford Churchill Hospital Headington

Oxford United Kingdom OX3 7LE -+44 1865 857264 priya.sugavanam@ocdem.ox.ac.uk Public Forrest Tin Wai Cheung https://orcid.org/0000-0003-4462-9639 Scientific

Sir Jules Thorn Sleep and Circadian Neuroscience Institute Nuffield Department of Clinical Neurosciences Dorothy Crowfoot Hodgkin Building University of Oxford South Parks Road

Oxford United Kingdom OX1 3QU +44 (0)1865 618697 forrest.cheung@ndcn.ox.ac.uk Public University of Oxford University/education https://ror.org/052gg0110 Non-commercial NIHR Central Commissioning Facility (CCF)