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

NHSBT Newcastle Blood Donor Centre Holland Drive

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

Pinewood House Pinewood PLACE

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

Bethlem Royal Hospital Monks Orchard Road

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

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

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

Robert Dolan House 9 Alie Street

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

Trust Headquarters 350 Euston Road Regents PLACE

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

NHS Foundation Trust Carholme Court Long Leys Road

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

Trust Hq Swandean Arundel Road

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

Carew House Beacon Technology Park Dunmere Road

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

Trust Headquarters Redesmere The Countess of Chester Health Park Liverpool Road

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

Trust Headquarters West Park Hospital Edward Pease Way

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

Harper Lane Shenley

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

Goodmayes Hospital 157 Barley Lane

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

18 Mole Business Park Randalls Road

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

Springfield Hospital 61 Glenburnie Road

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

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

London United Kingdom SE5 8AF +44 (0)20 7848 0002 rory.sheehan@kcl.ac.uk Public South London and Maudsley NHS Foundation Trust https://ror.org/015803449 Non-commercial National Institute for Health and Care Research http://dx.doi.org/10.13039/501100000272 55017737 true Investigating the Mechanisms of MIld Cognitive Impairment using Multimodal BiomarkERs and Non-InVAsive Brain Stimulation (MINERVA): a study in older adults with mild cognitive impairment and healthy controls comparing active and sham theta transcranial alternating current stimulation on homeostatic plasticity, neurophysiological biomarkers, and cognitive performance MINERVA Overall Study Objective: The main objective of this study is to explore the role of homeostatic plasticity in the onset and progression of mild cognitive impairment (MCI) using transcranial magnetic stimulation (TMS), while simultaneously examining its relationship with multimodal biomarkers (MRI, EEG, blood NF-L, and tau protein) and assessing the effect of theta transcranial alternating current stimulation (theta-tACS) on behavioral and physiological changes. Specific Objectives: 1. To evaluate the role of homeostatic plasticity in healthy and MCI subjects using a TMS algorithm that incorporates facilitative preconditioning with tDCS and rTMS and to correlate these findings with cognitive performance and multimodal MCI biomarkers. 2. To evaluate the predictive value of active versus sham theta-tACS on behavioral and physiological changes associated with MCI development, with a particular focus on the modulation of homeostatic plasticity parameters. Not provided at time of registration Homeostatic plasticity assessed by changes in motor evoked potential (MEP) amplitude in MCI patients compared to healthy controls, single-pulse TMS measurements - peak-to-peak amplitude of MEPs recorded via surface electromyography (EMG) of the right first dorsal interosseous (FDI) muscle, before and after facilitatory preconditioning (anodal tDCS and 5 Hz rTMS) baseline Homeostatic plasticity assessed by changes in MEP amplitude in MCI patients single-pulse TMS measurements - peak-to-peak amplitude of MEPs recorded via surface electromyography (EMG) of the right first dorsal interosseous (FDI) muscle, before and after facilitatory preconditioning (anodal tDCS and 5 Hz rTMS) baseline and 4 weeks (immediately post-intervention) Cognitive performance global cognitive status assessed by the Montreal Cognitive Assessment (MoCA) and specific cognitive domains (memory, executive functions, attention) measured via computerized tasks: Spatial Paired Associate Learning Task (S-PALT), Digit Span (DS) baseline and at 4 weeks (post-intervention) EEG spectral power and connectivity resting-state electroencephalography (EEG) recording using a 64-channel system, focusing on spectral power changes (specifically in theta and alpha bands) and functional connectivity measures to assess neural oscillation normalization, baseline and at 4 weeks (post-intervention) Plasma levels of neurodegeneration biomarkers concentrations of neurofilament light chain (NF-L) and Tau protein (total tau and p-tau181) measured from peripheral blood samples through Single Molecule Array (Simoa) technology baseline and at 4 weeks (post-intervention) Structural brain changes and white matter integrity magnetic resonance imaging (MRI) assessing hippocampal volume and periventricular white matter hyperintensities (WMH) using 3D T1-weighted and 3D T2-FLAIR sequences baseline and at 4 weeks (post-intervention) Ethics approval required The Ethical Committee of National Institute of Mental Health

Topolová 748

Klecany Czech Republic 250 67 113/25 10.1186/ISRCTN55017737 Interventional Randomized controlled trial Blinded (masking used) Placebo Parallel Diagnostic Treatment Not applicable 2029-06-01T00:00:00.000Z Czech Republic Germany true MCI: 1. Males and females aged 65 years and older with single- and multiple-domain amnestic MCI 2. Meet Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-V) criteria for Mild Neurocognitive Disorder as determined by Structured Clinical Interview for DSM-V (SCID-5) 3. The mental ability to understand and sign the Informed Consent Form 4. Montreal Cognitive Assessment (MoCA) score from 19 to 25 Age-matched controls: 1. Healthy males and females aged 65 years and older without single- and multiple-domain amnestic MCI and without subjective cognitive decline 2. The mental ability to understand and sign the Informed Consent Form 3. MoCA score ≥26 Senior 65 Years 100 Years All 120 0 1. Psychiatric comorbidity on axis I and II according to DSM-V 6 months before enrolment in the study 2. Personality disorder that makes participation in the trial difficult 3. History of substance dependence in the last year except for nicotine 4. Contraindications of TMS and tES: history of epilepsy or any neurologic condition likely to increase risk of seizure, mass brain lesions, cerebrovascular accident, metal in the head, a history of major head trauma with unconsciousness longer than 5 minutes), skin diseases (contraindications to tES) 5. Subjects with severe somatic disorders (cardiovascular disease, neoplasms, endocrinological disorders, etc) 6. Subjects treated with electroconvulsive therapy less than 3 months before enrollment or suffering from neurologic disorder (e.g., epilepsy, head trauma with loss of consciousness) and subjects using any treatment which can strongly affect EEG 7. Substantial suicidal risk as judged by the treating psychiatrist 8. Sensory and motor impairment precluding the participation on computer tests 9. Claustrophobia 2026-06-01T00:00:00.000Z 2028-06-01T00:00:00.000Z Diagnosis and treatment of mild cognitive impairment (MCI) in older adults Mental and Behavioural Disorders Observational Phase: Participants (older adults with Mild Cognitive Impairment [MCI] and healthy age-matched controls) undergo a series of baseline diagnostic measurements. These include cognitive performance testing (Montreal Cognitive Assessment [MoCA] and computerized tests: Paired Associate Learning Task, Digit Span, Tower of London), structural magnetic resonance imaging (MRI; 3D T1 and 3D T2-FLAIR), resting-state electroencephalography (EEG), and blood sample collection for neurofilament light chain (NF-L) and tau protein analysis. Additionally, participants undergo transcranial magnetic stimulation (TMS) measurements to assess cortical excitability and homeostatic plasticity, utilizing short intracortical inhibition (SICI), intracortical facilitation (ICF), and long intracortical inhibition (LICI) protocols, paired with anodal transcranial direct current stimulation (tDCS) and repetitive TMS (rTMS) preconditioning. Interventional Phase: Participants with MCI are randomly allocated to one of two parallel groups using a permuted block design with a fixed block size of 4. Active Intervention Group: Participants receive active theta transcranial alternating current stimulation (theta-tACS). The stimulation is applied via round conductive rubber electrodes at the F3-F4 EEG electrode positions. A current of up to 2 mA peak-to-peak (based on individualized current density estimation) at 4 Hz is administered for 20 minutes per session. Control Group: Participants receive placebo (sham) tACS. Electrodes are placed in the same F3-F4 positions, but the current remains close to 0 mA, except for a 90-second duration at the beginning and end of the session to mimic the physical sensation of active stimulation. Administration and Follow-Up: For both interventional arms, the schedule consists of 3 sessions per week, totalling 12 sessions over a 4-week period. After initial training in the laboratory, subsequent tACS applications are self-administered by the participant at home with online assistance from a researcher. All participants (both MCI and healthy controls) undergo follow-up cognitive testing at 1 year post-intervention. Description of Visits: Screening Visit (V-1) [Day -20 to -1] The following procedures/assessments will be performed: 1. Signed informed consent 2. Confirmation of inclusion and exclusion criteria 3. Demographic data collection 4. Anamnesis (environmental factors) and complete Medical History 5. Documentation of medication (check for adequate maintenance medication) 6. Assessment of Montreal Cognitive Assessment (MoCA) scale Between Screening Visit and Day 1, an MRI examination (Visit M) will be performed as a separate procedure prior to the baseline. Baseline Visit (V0) [Day 0 to 1] The following procedures/assessments will be performed for all participants: 1. Documentation of medication 2. Assessment of MoCA scale 3. Cognitive tests 4. EEG measurement 5. TMS measurement (including preconditioning tDCS and rTMS) 6. Blood collection WP2 (MCI group only): Randomization (permuted block design with a fixed block size of 4 to active or sham tACS group) The tES questionnaire and potentially the first tACS session may occur during this visit. Intervention Visits (T1 – T12) [Days 2 – 30] Applies only to WP2 (MCI group) The following procedures/assessments will be performed: 1. Study treatment administration (tACS) 2. tES questionnaire (recording of side/adverse events) Intervention: 12 sessions in total (three sessions per week) Intervention parameters: Duration: 20 minutes/session Area of stimulation: F3-F4 EEG electrode positions Patient position of application: sitting position Active group: 2 mA peak-to-peak current intensity, frequency 6 Hz - 80 Hz. Sham group: Current close to 0 mA, except for a 90s ramp-up/ramp-down duration at the beginning and the end of the session. End-of-Intervention Visit (V1) [Day 30 ± 2] The following procedures/assessments will be performed: 1. Assessment of MoCA scale 2. Cognitive tests 3. EEG measurement 4. TMS measurement (including preconditioning tDCS and rTMS) 5. Blood collection 6. WP2 (MCI group only): Side/adverse effect questionnaire (tES questionnaire) completion (if not fully completed at the end of T12). WP2: Follow-up Visit (V2) [1-year FU] The following procedures/assessments will be performed: 1. Documentation of medication 2. Assessment of MoCA scale 3. Cognitive tests If the patient withdraws consent within follow-up (late drop-out), an unscheduled visit X-FU will be carried out to exclude side effects or worsening of clinical status and to record reasons for withdrawal. Device Not Applicable HDCStim stimulator (NeuroConn) The datasets generated during and/or analysed during the current study will be available upon request and will be published as a supplement to the results publication. Data will be made available following study completion through the European Open Science Cloud (EOSC) Portal (https://eosc-portal.eu/) in accordance with FAIR principles. Data will be stored pseudonymised in RedCap (NIMH) and secuTrial® (UMG) databases, accessible only to authorised personnel in compliance with EU GDPR. Data types include behavioural data, assessment scales, electrophysiological data (EEG, TMS), MRI/fMRI, and physiological data. Available on request

b6603f26-ea8a-455c-a8ae-52069f8f686a ed6c0091-8056-452e-b237-bbd0b7789b9a fe939974-464d-49d2-abcd-47e4880da6b3 Yes Statistical Analysis Plan 49592_SAP.pdf e209468a-5d89-42d3-a45b-8dbd5925e795 true application/pdf 153923 89518d9aee43f8323717a84172f5b7cb Monika Klírová https://orcid.org/0000-0002-8092-9586 Scientific Principal investigator Public

Topolová 748

Klecany Czech Republic 250 67 +420 (0)283088148 monika.klirova@nudz.cz Public National Institute of Mental Health https://ror.org/05xj56w78 Non-commercial Ministry of Health of the Czech Republic 18103637 true Examining the effectiveness, cost-effectiveness and mechanisms of 'Learning Together for Mental Health' on mental health outcomes: a nested, cluster randomised controlled trial in English secondary schools The study aim is to examine the effectiveness, cost-effectiveness and mechanisms of the 'Learning Together for Mental Health' (LTMH) whole-school intervention in terms of its mental health outcomes in a cluster randomised controlled trial and answer the following research questions: 1. What are the effects of LTMH in intention-to-treat (ITT) analyses on student-reported psychological difficulties (primary outcome), and various pre-hypothesised secondary mental health outcomes? 2. Are effects moderated by student baseline mental health, sex, gender, ethnicity, deprivation or sexual orientation, or school characteristics? 3. Are effects greater in analyses accounting for intervention fidelity? 4. What are the effects for pre-specified subgroups (students eligible for free school meals, students with higher reported psychological difficulties at baseline, student with non-white ethnicity, sexual minorities, girls and boys)? 5. Is the intervention cost-effective? 6. What do qualitative and quantitative data suggest about mechanisms by which the intervention generates mental health impacts? 7. What do the trial findings suggest about the intervention theory of change and transferability? Background and study aims Adolescence is an important period when many mental health problems emerge. These problems tend to worsen during secondary school. Poor mental health in adolescence can lead to problems such as self-harm, suicide, drug and alcohol dependence, poor school attendance and lower educational achievement. Mental health problems in adolescence can also have lasting effects for physical, social and mental wellbeing in adulthood. Programs in schools that target the context and culture, rather than individual students, are a promising way to improve student mental health. Some years ago, we tested such a program (called Learning Together) to reduce bullying in English secondary schools. We found that this program not only reduced bullying but also improved student mental health and GCSE results. We worked with the latest research, teachers and students, to adapt this program so it directly focused on mental health. We called it ‘Learning Together for Mental Health’ (LTMH). We also tested this new LTMH program in four secondary schools. We found it was well-liked and considered useful by teachers and students. An educational charity, the Education Endowment Foundation (EEF), is running large study with 140 schools to see if LTMH can improve educational achievement. We want to embed a mental health study, looking at effect of LTMH on mental health, in all these schools. EEF will not measure the mental health effect of LTMH as that is out-of-scope for them. It would represent very good value to also learn mental health effects within the same study. As a part of the mental health study, we aim to examine whether the LTMH program can improve student mental health, whether it works better for certain types of schools or students, and whether is offers a good value for money. We also aim to understand how it works, for whom and under what circumstances and how best it can be used in other settings, if needed. Who can participate? All state-funded, mainstream secondary schools in England can take part in the study so long as the senior leadership team is able to commit to participation for the whole duration of the program and pay the participation costs. What does the study involve? LTMH is a whole school program and involves training teachers to use a method call restorative practice. This differs from punishment-based methods by focusing instead on building relationships. It helps teachers model empathic conversation and manage conflict. The persons in a conflict can explain how they feel and take responsibility to find a way ahead. This helps heal relationships and prevents future problems. LTMH also involves setting-up of an ‘action group’ in each school, made up of teachers and students. Teacher and students work together to look at information collected from the students about their mental health alongside a manual with effective things to do for mental health. The action group then plan and make changes so the school feels more supportive. To study the impact of the program on student mental health, students in year-7 or year-8 in all 140 schools will fill-out a questionnaire about their mental health (this will be collected as a part of the EEF study). Through random choice, 70 schools will then get the LTMH program, while 70 will carry on with their normal approach. Schools that get the LTMH program will get staff training for restorative practice, support to deliver action groups and a manual. We will make sure LTMH is inclusive and accessible to all students. Three years later, students in all 140 schools (now in year-10) will fill-out a questionnaire again. We will compare results to see if students in the schools that got the LTMH program report better mental health. We will also look at how much the program costs, and talk to teachers and students about their thoughts on LTMH. This will help us know whether LTMH works, whether it’s good value for money and whether it could be used in secondary schools across the country. What are the possible benefits and risks of participating? If LTMH works, it could be used in schools across England to help improve mental health for thousands of young people. We will share our findings widely with schools, teachers, parents, students, charities, policymakers and the government to make sure they lead to real change. Participating schools will also get some financial compensation for taking part. Risks of participation are minimal but may include individuals feeling upset about something while completing the questionnaires or interviews. We have protocols in place to provide support to participants if this should happen. Where is the study run from? The mental health study is being led by a team of research from the London School of Hygiene & Tropical Medicine and University College London. The study of educational impacts of the LTMH programme is being done by a team of researchers from Anna Freud and Ipsos. When is the study starting and how long is it expected to run for? School recruitment for EEF’s large study on educational impacts began in March 2026 and is currently ongoing. The mental health study that we are embedding in this large study will use information collected from EEF’s study and will begin in September 2026. Who is funding the study? The embedded mental health study is funded by the National Institute of Health and Care Research, UK. The LTMH program is being funded by EEF as a part of their large study. Who is the main contact? Dr. Neisha Sundaram, London School of Hygiene & Tropical Medicine Psychological difficulties Strengths and Difficulties Questionnaire (SDQ) Total Difficulties score Year 10 through endline surveys Emotional problems, conduct problems, peer problems and hyperactivity SDQ subscales Year 10 through endline surveys Mental wellbeing Short Warwick-Edinburgh Mental Well-being Scale Year 10 through endline surveys Eating problems and weight and shape cognitions Eating problems and weight and shape cognitions (EDE-QS) Year 10 through endline surveys Bullying victimization Gatehouse Bullying Scale Year 10 through endline surveys Ethics approval required

10.1186/ISRCTN18103637 NIHR: 506643 506643 Interventional Randomized controlled trial Open (masking not used) Active Cluster Prevention Not applicable 2029-12-31T00:00:00.000Z United Kingdom England Schools in England

England

England England England true 1. State-funded, mainstream secondary schools in England 2. Senior leadership team (SLT) is able to commit to intervention, pay participation costs and sign Memorandum of Understanding (The impact evaluation will include students in year 7 for schools that completed baseline surveys in the summer term of 2026, or students in year 8 for schools that complete baseline surveys in the autumn term of 2026) Mixed 10 Years 70 Years All 140 0 1. The school’s most recent Ofsted rating is inadequate (based on the previous Ofsted grading). If the school has had an inspection since January 2026 with the new Ofsted grading criteria, schools that do not meet minimum safeguarding expectations and schools that receive an ‘urgent improvement’ grade in the ‘leadership and governance’ evaluation area will be excluded. Those schools will not be included, as the research has shown that schools require a minimum level of institutional capacity to implement the intervention. 2. The school is enrolled in another mental health or wellbeing intervention study. Note that schools involved in descriptive surveys or small pilot projects (e.g. with psychology students) will not be excluded 3. The school is enrolled in any other EEF trial currently that is also focused on mental health 4. The schools involved in the LTMH feasibility study 2026-03-02T00:00:00.000Z 2026-10-31T00:00:00.000Z Preventing mental health problems and improving wellbeing among secondary school students Mental and Behavioural Disorders This study involves a cluster randomised controlled trial (RCT) to examine the effectiveness, cost-effectiveness and mechanisms of the 'Learning Together for Mental Health' (LTMH) program in terms of its mental health outcomes for students, nested within the Education Endowment Foundation (EEF)'s trial assessing the impact of LTMH on educational outcomes. As part of the EEF trial, all pupils in Year 7 (Spring/Summer 2026) or Year 8 (Autumn 2026) in 140 schools will be invited to take part in an online survey completed in school. Schools are the unit of randomisation and are allocated on a 1:1 basis to the intervention and control arms, stratified by school-level factors: school-level deprivation (% students eligible for FSM below or above the median in England for the year); special education needs (SEN) status (proportion of students with SEN and disabilities); and attainment (Progress 8 score school average above and below median of 0 for England), by a researcher not involved in the statistical analysis from the Education Trial evaluation team. A first set of schools that completed ≥ 80% of responses on the baseline survey by the end of the summer term 2026 were randomised simultaneously in a block in late July 2026. Schools that complete their baseline surveys after this are being randomised on a weekly rolling (sequential) basis. Intervention: Learning Together for Mental Health (LTMH) is a whole-school, multicomponent, facilitated intervention that involves four key elements in each school. a) Formation of student and staff co-led Action Group (AG). It is empowered to modify school mental health and disciplinary policy. The AG will be facilitated by Place2Be staff. The AG will meet twice per term across each year of implementation, meeting more frequently if needed. The AG can draw on the following: (i) A student needs assessment report (NAR), drawing on the instruments and measures included in the baseline student survey. This provides the AG with data on their school’s prevalence of various needs, such as psychological problems, conduct problems, peer relationship problems, self-harm, eating problems, bullying, substance use and anti-social behaviour; (ii) An intervention manual including an evidence-based menu of effective mental health actions and strategies at the school level which have been previously shown to improve aspects of menatal health and wellbeing in young people. The Place2Be facilitator will guide the AG in using the menu and selecting actions from the menu that address the priorities identified for the school. The manual will also provide guidance on setting up and running inclusive AGs. b) Facilitation: The AGs are facilitated by a trained facilitator with expertise in school mental health, employed, supervised and trained by Place2Be. Place2Be will employ a lead facilitator who will manage and supervise these facilitators. Each school will receive seven half-day sessions of in-person facilitation in the first year of implementation and six sessions in the second year, supported by the same facilitator across the intervention. Online support from facilitators will be available to schools between in-person visits. In the third year of implementation, AG chairs will facilitate the AGs, supported by Place2Be where required. c) All-staff introductory training in restorative practice (RP) which aims to prevent and address conflict and thereby improve mental health via improving relationships. All staff are trained to implement primary RP through empathic communication and working ‘with’ students. d) In-depth training in RP for selected staff to facilitate meetings in which bullying victims are empowered to communicate harms, while perpetrators are encouraged to acknowledge these and take responsibility for their behaviour to repair relationships and prevent future conflict, thus contributing to improved mental health. The intervention will be a three-year programme, fully facilitated by Place2Be for the first two years and with light-touch support for schools from Place2Be in year 3. Schools will be encouraged to continue implementation independently in a fourth year, after which the educational evaluation will take place. Control: Control schools will continue their usual practice regarding existing relationships, sex and health education and mental health provision to maximise trial external validity A process evaluation (PE) will be conducted to explore mechanisms underlying mental health impacts and implementation. For this, in four case study schools, two staff members will be invited to participate in interviews every year for three years of the intervention. Students will also be invited to participate in two student focus groups per year of the intervention in each of the four case-study intervention schools. Behavioural Not expected to be made available ee405987-105e-4f45-b0f6-86d0687ed655 28327406-ca08-41d3-91c3-b26cc864b31d 1451ff06-9e7e-492e-a868-5682c9b8270f 254155fd-3877-47a0-b530-63e46bae3867 No Neisha Sundaram https://orcid.org/0000-0003-4159-9518 Principal investigator Public Scientific

15-17 Tavistock Place London School of Hygiene & Tropical Medicine

London United Kingdom WC1H 9SH +44 (0)20 7636 8636 neisha.sundaram@lshtm.ac.uk Public Russell Viner https://orcid.org/0000-0003-3047-2247 Principal investigator

University College London, UCL Great Ormond St. Institute of Child Health, UK, 30 Guilford St.

London United Kingdom WC1N 1EH +44 (0) 20 7679 2000 r.viner@ucl.ac.uk Public London School of Hygiene & Tropical Medicine https://ror.org/00a0jsq62 Non-commercial National Institute for Health and Care Research http://dx.doi.org/10.13039/501100000272 90928609 true A multicenter implementation study of the Multifamily intervention in Guatemala and Bolivia CONECTA 1. Identify the barriers and facilitators to implementing the Multifamily Group (MFG) intervention, including social prescribing, in community and primary healthcare settings in Bolivia and Guatemala 2. Assess the acceptability, adoption, appropriateness and feasibility of implementing the MFG intervention, including social prescribing, in these settings 3. Explore the initial penetration of the MFG intervention, including social prescribing, in these settings 4. Assess changes in clinical and wellbeing outcomes among patients and their caregivers following participation in the MFG intervention Background and study aims Long-term physical conditions such as diabetes, obesity and high blood pressure are very common, and people living with them often also experience anxiety, depression or a low quality of life. Current healthcare tends to focus on the physical illness alone, even though family support and community connections can make a big difference to how well people manage their condition. This study will introduce and test "Multifamily Groups" (MFG), where several families facing similar health challenges meet regularly with one or two trained facilitators to share experiences, learn from one another and build coping strategies. The programme also includes "social prescribing", connecting participants with helpful non-medical services in their community. The study will find out whether this approach is acceptable, adopted, appropriate and feasible in community and primary healthcare settings in Bolivia and Guatemala, and whether it is associated with changes in participants' wellbeing. Who can participate? Adults (18 years or older) who have a physical non-communicable disease (diabetes, obesity or hypertension) and who also have a low quality of life or signs of anxiety or depression, together with a caregiver, family member or friend who is willing to take part with them. Health professionals and community members who will facilitate the group sessions may also take part. What does the study involve? Participants will be screened and complete some short questionnaires about their health, wellbeing and quality of life. Families will then take part in Multifamily Group sessions over about six months, meeting regularly to discuss topics they choose, with support from trained facilitators. Participants will also be linked to relevant community resources through social prescribing. Questionnaires and interviews will be repeated at 6 and 9 months to see how participants and the programme are getting on. What are the possible benefits and risks of participating? The study is expected to carry a low risk of physical or mental harm. Some of the topics discussed in sessions, or the questions asked in interviews, may occasionally be sensitive or cause some distress; support and referral arrangements are in place if this happens. Participants may benefit from peer support, improved coping strategies, and connection to helpful community resources, although this cannot be guaranteed as this is a study of how the programme works in practice rather than a treatment trial. Where is the study run from? Community and primary healthcare settings in Bolivia (Santa Cruz de la Sierra metropolitan region and San José de Chiquitos) and Guatemala (Alta Verapaz, Quetzaltenango and Guatemala City), led by Universidad Privada Franz Tamayo (Bolivia) and Universidad Rafael Landívar (Guatemala), in partnership with Queen Mary University of London (UK) and Pontificia Universidad Javeriana (Colombia). When is the study starting and how long is it expected to run for? October 2026 to September 2027. Who is funding the study? The National Institute for Health and Care Research (NIHR), through its Global Health Research Centre programme (grant NIHR203266). Who is the main contact? juan_marin@javeriana.edu.co Barriers and facilitators to implementation of the Multifamily Group (MFG) intervention semi-structured interviews and focus groups with patients, caregivers and moderators, analysed deductively using the Consolidated Framework for Implementation Research (CFIR) 6 and 9 months after baseline Acceptability of the Multifamily Group (MFG) intervention acceptability of Intervention Measure (AIM), self-completed by patients, caregivers and moderators; supplemented by semi-structured interviews 6 months after baseline Appropriateness of the Multifamily Group (MFG) intervention Intervention Appropriateness Measure (IAM), self-completed by patients, caregivers and moderators 6 months after baseline Feasibility of the Multifamily Group (MFG) intervention Feasibility of Intervention Measure (FIM), self-completed by patients, caregivers and moderators; supplemented by semi-structured interviews 6 months after baseline Adoption of the Multifamily Group (MFG) intervention semi-structured interviews and focus groups with patients, caregivers and moderators, analysed deductively using the implementation outcomes taxonomy of Proctor et al. 6 months after baseline Initial penetration of the Multifamily Group (MFG) intervention follow-up semi-structured interviews and focus groups with patients, caregivers and moderators, analysed deductively using CFIR Domain V and Proctor's penetration construct; social prescribing referral and uptake records 9 months after baseline (6-9 month maintenance period) Health-related quality of life in patients and caregivers EQ-5D-5L and MANSA , interviewer-administered Baseline and 6 months after baseline Treatment adherence in patients Treatment Adherence Visual Analogue Scale (VAS), interviewer-administered Baseline and 6 months after baseline Lifestyle in patients FANTASTIC Lifestyle Assessment Scale, interviewer-administered Baseline and 6 months after baseline Caregiver burden Zarit Burden Interview (short version), interviewer-administered Baseline and 6 months after baseline Depressive symptoms in patients and caregivers Patient Health Questionnaire-8 (PHQ-8), interviewer-administered Baseline and 6 months after baseline Anxiety symptoms in patients and caregivers Generalized Anxiety Disorder-7 (GAD-7), interviewer-administered Baseline and 6 months after baseline Ethics approval required Institutional Research Bioethics Committee, Dr. Mario Ortiz Suarez Children's Hospital

Santa Barbara Street, between Buenos Aires and Seoane - Pilot

Santa Cruz de la Sierra Bolivia - Ref. CBI-HNMOS 006/2026 (International Code: FWA0002426) Ethics Committee of the Faculty of Health Sciences, Universidad Rafael Landívar

Campus Central, Vista Hermosa III, Zone 16, Building "L", Office L-308, 3rd Floor

Guatemala City Guatemala 01016 CE-FCCSS/URL-(NIRH-QMUL-P.I_PS27072026) Queen Mary University of London Ethics Committe

Research Services, Dept. W, 69-89 Mile End Rd

London United Kingdom E1 4UJ 2688 10.1186/ISRCTN90928609 Interventional N/A: single arm study Open (masking not used) Uncontrolled Single Health services research Treatment Not applicable 2027-09-10T00:00:00.000Z Bolivia Guatemala false Patients: 1. Aged 18 years or older 2. A low MANSA quality-of-life score (≤5) or a high GAD-7 or PHQ-8 score (≥10) 3. A known prior diagnosis of a physical non-communicable disease (diabetes, obesity or hypertension) 4. Have at least one caregiver or family member/friend who can be invited to participate 5. Able to speak and understand Spanish 6. Receiving treatment or management for their non-communicable disease through a public or private primary healthcare centre, outpatient service or community healthcare setting Caregivers: 1. Self-identify as a caregiver or support person (family member, friend or non-professional caregiver) of an enrolled patient 2. Aged 18 years or older 3. Able to speak and understand Spanish Moderators: 1. A health professional or community member (community leader or community health worker, including traditional healers) 2. The lead moderator must be a health professional, with a community member able to act as co-moderator Mixed 18 Years 100 Years All 120 0 Patients and caregivers: 1. Current participant in the DIALOG+ trial 2. Current participant in a trial involving any psychosocial or psychological intervention 3. Current participant in a trial involving the testing of any psychiatric medication Caregivers (additional): 1. Professional caregiver (a trained and paid person providing health-related or personal care as part of a formal paid role) 2. Previous participation in the Latin American Multifamily Group Intervention pilot study Moderators: 1. A temporary employee or a person not planning to remain in the clinical service for 6 months 2. Health workers under 18 years of age 2026-10-15T00:00:00.000Z 2026-12-31T00:00:00.000Z Physical non-communicable diseases (diabetes, obesity or hypertension) with comorbid psychological distress (anxiety and/or depression) or low quality of life Other Multifamily Group (MFG) intervention: brings together 5 to 8 families of patients with similar non-communicable disease and mental health/wellbeing problems in a structured group setting, facilitated by one or two trained moderators. Regular sessions are conducted over a six-month implementation period through a three-way dialogue between moderators, patients and family members/caregivers. Meetings focus on topics selected by the group, such as family dynamics, illness-related stigma, medication, psychological treatment options, crisis management, social integration and vocational support. Moderators guide psychoeducation, problem-solving and mutual support, while ensuring equitable participation, adherence to ground rules, confidentiality and coherent group organisation; additional experts may be invited when appropriate. The final session includes an assessment of participants' experiences, followed by encouragement for the group to hold at least two participant-led meetings during a subsequent three-month period without the research team present. The intervention also incorporates social prescribing, with the moderator (who may act as a link worker) connecting participants with non-medical community resources and services addressing the social determinants of their health and wellbeing. Behavioural Not expected to be made available 5d7b6e4b-7713-4e17-bf1a-79eb7a49ce74 8454035a-96b1-4d34-a8d8-44cf27f9a727 a10b40d3-fb00-43ce-97af-2dfaa4735e63 4938e17a-25e5-4fbb-9f97-3b0b4be51cba 54c13ca2-4762-4ebd-821c-085ed145f190 4bac3d6f-baf9-4aef-8667-04345268ee48 72781c1e-4d63-427e-8c48-dbc3dedd9df7 No Victoria Bird https://orcid.org/0000-0002-2053-7679 Principal investigator

Wivenhoe Park

Colchester United Kingdom CO4 3SQ - v.bird@essex.ac.uk Public Juan Marin Scientific Public

Unit for Adult Mental Health & Wellbeing  Centre for Psychiatry and Mental Health  Wolfson Institute of Population Health  Queen Mary University of London Yvonne Carter Building

London United Kingdom E1 2AB  - j.c.marin@qmul.ac.uk Public Sana Sajun Public Scientific

Unit for Adult Mental Health & Wellbeing  Centre for Psychiatry and Mental Health  Wolfson Institute of Population Health  Queen Mary University of London Yvonne Carter Building

London United Kingdom E1 2AB  - s.sajun@qmul.ac.uk Public Edgar Miguel Lopez Alvarez https://orcid.org/0000-0002-6619-4149 Principal investigator

Ciudad de Guatemala

Guatemala Guatemala 9999 +502 (0)40173026 emlopeza@url.edu.gt Public Ronald Fernando Tapia Pijuan Principal investigator

Santa Cruz de la Sierra

Santa Cruz de la Sierra Bolivia 999 +591 (0)78510007 ronaldfernandotp@hotmail.com Public Queen Mary University of London https://ror.org/026zzn846 Non-commercial National Institute for Health and Care Research http://dx.doi.org/10.13039/501100000272 54091957 true PuntoCare: Digital post-diagnosis support platform for MCI and early dementia Primary objective: To assess the feasibility of implementing PuntoCare within NHS memory services. This includes: 1. The ability to recruit the target number of participants across sites 2. Participant retention over the 24-week intervention period 3. Feasibility of integrating the platform within routine clinical pathways Secondary objectives: 1. To evaluate the usability and acceptability of PuntoCare amongst patients, carers, and clinicians 2. To assess participant engagement with the platform, including usage patterns and feature utilisation 3. To generate preliminary health economics data through a cost-consequence analysis conducted from an NHS perspective 4. To explore the impact of PuntoCare on CST-equivalent support, including programme offer, uptake, completion, dropout, and total sessions delivered 5. To explore the potential impact of PuntoCare on memory service waiting lists, including changes in waiting list size and average waiting time Exploratory objectives: 1. To estimate key parameters to inform a future definitive effectiveness trial (e.g. quality of life, carer burden, and service costs) Background and study aims After diagnosis with mild cognitive impairment (MCI) or dementia, many people in the UK receive little structured support. Only 16% of people with dementia say they get adequate support from memory clinics, GPs, or charities. Over half of families experience a dementia-related crisis within a year, and carers often feel stressed and anxious. PuntoCare is a smartphone app designed to help people with MCI or early dementia, and their carers, manage life after diagnosis. It provides daily personalised activities, including memory exercises, physical activity, educational information, and a symptom diary to track changes over time. This study will test whether PuntoCare can work well within NHS memory services. We'll check if people can be recruited and stay in the study, if the app fits into routine care, and if people find it acceptable and easy to use. Who can participate? You can participate if you: • Are aged 50 years or over • Are able to give informed consent • Have one of the following: subjective memory concerns, mild cognitive impairment, mild dementia, or no memory concerns (as a healthy comparison volunteer) • Have sufficient English to complete the study procedures and use the digital app • Are willing and able to use the PuntoCare app over the 24-week study period • Have access to a compatible smartphone or tablet, either your own or via a carer You cannot participate if you have: • Moderate or severe dementia, or any condition that affects your ability to give informed consent • Severe sensory, motor, or cognitive impairments that would prevent you from using the digital app, even with support • Acute or unstable physical or mental health problems that, in the opinion of the clinical team, would make participation inappropriate What does the study involve? Participants will use the PuntoCare app for 24 weeks (about 6 months). They'll get training and support from a research nurse to get started. They'll complete short surveys in the app about their wellbeing and how they're getting on with the app. Some participants may be invited to take part in a short interview at the end. There are no extra hospital visits needed; everything fits around usual care. What are the possible benefits and risks of participating? Benefits: Your participation will help us understand whether PuntoCare can be successfully used within NHS memory services and whether it improves wellbeing and support for people with memory difficulties. The findings could benefit many people with mild cognitive impairment or dementia in the future and help improve post-diagnosis support across the NHS. Taking part may not directly benefit you personally. However, you will have free access to Punto-Care throughout the 24-week study, and you will be able to continue using the app at no cost after the study ends. You will also receive regular support from a research nurse during the study. Your participation also contributes to valuable research that could shape how the NHS delivers care for people with memory concerns in the future. Risks: There are no known medical risks associated with taking part in this study. The main activity involves using the PuntoCare app at home over 24 weeks and completing short questionnaires about your wellbeing. Some people may find reflecting on memory difficulties slightly stressful or upsetting, or may experience technical issues with the app. The app is designed to be supportive and positive, and the research team are trained to respond sensitively if any concerns arise. You can withdraw from the study at any time, and you are free to take breaks from using the app whenever you need to. If you find anything difficult, you can speak to the research team for sup-port. Your participation will not affect your usual care in any way. Where is the study run from? The study is conducted across two NHS sites in England: • North London NHS Foundation Trust • Oxleas NHS Foundation Trust • Gallions Reach Health Centre, as Participant Identification Centre. When is the study starting and how long is it expected to run for? The study is expected to start in September 2026, depending on site setup. We will recruit participants over approximately 12 months (from September 2026 to July 2027). Data analysis is anticipated to be completed by December 2027, although this date is indicative and may change de-pending on recruitment progress and data collection completion. Who is funding the study? The National Institute for Health and Care Research (NIHR) i4i FAST Programme. Punto Health Ltd is sponsoring the research. Who is the main contact? Maria Rollano Corroto, maria@puntohealth.com Participant retention recruitment and retention records 24 weeks Data completeness Case Report Form (CRF) and questionnaire completion rates baseline and week 24 Feasibility of integration within routine clinical pathways qualitative interviews with healthcare staff and site teams involved in the study (assessing implementation feasibility, barriers, and facilitators) week 24 (end of study) 1. Usability and acceptability of the PuntoCare platform among patients, carers and clinicians measured using Customer Satisfaction (CSAT) questionnaires at day 7, day 30 and day 74, the Net Promoter Score (NPS) at day 30 and day 74, User Perception surveys at day 21 and day 63, and optional semi-structured qualitative interviews with a subset of patients and carers to gather detailed feedback on usability and acceptability at week 24 (end of study) 2. Participant engagement with the PuntoCare platform, including frequency and patterns of use measured using in-app telemetry data (logins, module access, session duration, feature utilisation) collected continuously throughout the 24-week study period 3. Uptake, completion and delivery of CST-equivalent support measured using NHS trust service utilisation records and PuntoCare app data (number of patients offered, started, completed, and dropped out) at baseline and week 24 4. Memory service waiting list size and waiting times measured using NHS trust administrative data on waiting list size and average waiting times at baseline and week 24 5. Intervention costs and resource use associated with implementation of PuntoCare measured using Cost-Consequence Analysis (CCA) from an NHS perspective, including intervention delivery costs (licensing, training, ongoing support), healthcare resource use (memory clinic contacts, CST activity), waiting list metrics (size and average waiting time), and CST-equivalent delivery metrics (uptake, completion, dropout), at baseline and week 24 EXPLORATORY OUTCOMES: 1. Patient wellbeing measured using the WHO-5 Well-Being Index at baseline and every 2 weeks 2. Patient self-efficacy measured using the New General Self-Efficacy Scale (NGSE) at baseline and every 2 weeks 3. Carer burden measured using the Zarit Caregiver Burden Scale (short form) at day 0 and day 70 4. Patient quality of life measured using the EQ-5D-5L at baseline and week 24 5. Participant, carer and clinician experiences of the intervention, including barriers and facilitators to implementation measured using semi-structured qualitative interviews at end of study (week 24) 6. Product-market fit measured using the Sean Ellis Product Market Fit questionnaire at day 74 Ethics approval required Yorkshire & The Humber - Bradford Leeds Research Ethics Committee

2 Redman Place, Stratford

London United Kingdom E20 1JQ 26/YH/0128 10.1186/ISRCTN54091957 367218 CPMS: 72016, NIHR: 510915 367218 72016 510915 Interventional Non-randomized controlled trial Open (masking not used) Uncontrolled Single Treatment Not applicable 2027-12-17T00:00:00.000Z United Kingdom England OXLEAS NHS Foundation Trust - Greenwich Memory Service

Memorial Hospital, Shooters Hill, Woolwich

London England SE18 3RG North London NHS Foundation Trust - Enfield Memory Service (EMS)

Chase Farm Hospital, The Ridgeway, Enfield

London England EN2 8JL Gallions Reach Health Centre (Participant Identification Centre (PIC) only)

Bentham Road

London England SE28 8BE G83012@2.16.840.1.113883.2.1.3.2.4.18.48 true Patients: 1. Adults aged >=50 years 2. Capacity to provide informed consent 3. Individuals in one of the following groups, as determined through routine clinical assessment and application of the following criteria: - Subjective Cognitive Decline (SCD; also referred to as Subjective Memory Complaints, SMC): The following criteria will be used to define SCD (Jessen et al., 2014): (1) Self-experienced persistent decline in cognitive capacity compared with a previously normal status (2) Normal performance on standardised cognitive assessments (3) No significant impairment in activities of daily living (4) Absence of mild cognitive impairment or dementia - Mild Cognitive Impairment (MCI): An individual meeting the following diagnostic criteria will be identified as having MCI (Albert et al., 2011): (1) Concern regarding a change in cognition, whether reported by the self, informant, or clinician. (2) Objective evidence of impairment in one or more cognitive domains, typically including memory. (3) Preservation of independence in functional abilities. (4) Absence of dementia. - Mild dementia: An individual meeting the following diagnostic criteria will be identified as having mild dementia (DSM-5, 2013): (1) Evidence of cognitive decline from a previous level of performance, reported by the individual, an informant, or a clinician (2) Objective impairment in one or more cognitive domains (e.g. memory, attention, language, executive function) (3) Interference with independence in everyday activities (e.g. requiring assistance with complex tasks) (4) Not better explained by delirium or another mental disorder - Healthy controls: An individual meeting the following diagnostic criteria will be identified as a healthy control: (1) No self-reported cognitive concerns (2) Normal performance on a standardised cognitive assessment, defined as a score of >=27 on the Mini-Mental State Examination (MMSE) (Molloy & Standish, 1997) (3) No clinical diagnosis of mild cognitive impairment or dementia (4) Independent in activities of daily living 4. Sufficient proficiency in English to complete the study procedures and use the digital platform 5. Willingness and ability to engage with the PuntoCare digital platform over the study period 6. Access to a compatible smartphone capable of running the PuntoCare application, either personally or via a carer. Carers (participation is voluntary and not required for patient enrolment): 1. Age >=18 years 2. Named carer of an eligible enrolled patient 3. Capacity to provide informed consent 4. Sufficient proficiency in English 5. Able and willing to participate in study procedures Mixed 50 Years 120 Years All 90 0 Patients: 1. Moderate or severe dementia, or any condition associated with lack of capacity to provide informed consent 2. Severe sensory, motor, or cognitive impairments that would prevent completion of the study procedures, including use of the digital assessment tools, even with support 3. Acute or unstable physical or mental health conditions that, in the opinion of the clinical team, would make participation inappropriate Carers: 1. Lack capacity to provide informed consent 2026-09-28T00:00:00.000Z 2027-07-31T00:00:00.000Z Dementia and neurodegeneration Nervous System Diseases This is a multi-site feasibility study with an embedded health economics evaluation. The study is designed to assess the feasibility of implementing PuntoCare within NHS primary and secondary care settings, alongside an exploratory evaluation of usability, acceptability, and service-level impact. The study design has been informed by Patient and Public Involvement and Engagement (PPIE) activities, incorporating feedback from lived-experience representatives to ensure relevance and acceptability to patients and carers. Participants will engage with the PuntoCare digital platform over a 24-week intervention period, integrated within routine post-diagnosis care pathways. Where appropriate, carers may also take part alongside participants. Health economic evaluation will be conducted using a cost-consequence framework from an NHS perspective, focusing on delivery of CST-equivalent support and potential impact on memory service waiting lists. Study procedures Following informed consent, participants will be onboarded onto the PuntoCare platform and supported by a research nurse to initiate use of the intervention within routine care pathways. No additional in-person study visits are required beyond those aligned with routine clinical care. Participants will use the PuntoCare mobile application over a 24-week period. The application comprises three main components: 1. Daily Care Plans: Participants will be guided through structured daily care plans, which include: - Adaptive cognitive stimulation exercises (evidence-based CST activities) - Video-based physical exercise protocols (tailored to mobility level) - Guided relaxation sessions - Healthy habits suggestions - Rewards system and progress tracking to support engagement 2. Resource Library of clinically validated educational modules and articles related to cognitive impairment and dementia management and care strategies, adapted to each participant’s diagnosis and stage 3. Symptom Diary: allowing users, primarily carers, to log cognitive and behavioural symptoms over time. Participants will receive structured support throughout the study, including: • Onboarding workshops (digital literacy guidance, peer support, and device setup) • Weekly contact during the first month (intensive support phase) • Periodic check-ins at weeks 6, 12, and 24 • Ongoing technical support via email (pilots@puntohealth.com) • In-app support form available throughout the study Other The datasets generated during and/or analysed during the current study will be stored in a non-publicly available repository - Repository name/location: Google Cloud Platform (managed by Punto Health Ltd) - Type of data: Pseudonymised app engagement data, survey responses - When available: Following completion of data analysis (estimated late 2027/early 2028) - Duration: 10 years post-study completion - Access criteria: Restricted to authorised Punto Health - Access mechanism: Controlled via multi-factor authentication; audit trail maintained - Consent obtained: Yes. All data protection measures, retention period, and potential future use are detailed in the Participant Information Sheet. Participants provide explicit informed consent to these arrangements by signing the Consent Form, which includes statements confirming understanding of data processing, pseudonymisation, and potential sharing for future research and publication in anonymised form. - Data anonymisation: Pseudonymised with unique codes; direct identifiers removed- Ethical/legal restrictions: NHS REC approved; GDPR-compliant; Data Protection compliant - Comments: Data will be aggregated and fully anonymised before any sharing or publication. Anonymised data may be used to support future research building on this study, shared with other researchers as part of future studies, and presented in scientific publications and presentations. No individual participant results will be identified Stored in non-publicly available repository Protocol

1d8f7500-08f7-46bc-b537-e0549ef1ce17 fcad0717-e31f-462d-8638-a9ff247f8154 09545e19-d4f8-4b7d-8399-71e196008cc5 0d5de063-8d21-4660-b891-280c935d697a 7873cd02-d1a6-4787-a49b-75b24d4944ad Yes Protocol file ISRCTN54091957 Research_Protocol_v3.0 14Aug2026.pdf cd0b0c99-ff18-4963-bce8-f3ee2a9acd28 true application/pdf 834740 8f9cc597a3b2e2ade14dad5b22c4104d Maria Rollano Corroto https://orcid.org/0009-0005-8185-4474 Scientific Public

Health Foundry, 1 Royal Street

London United Kingdom SE1 7LL - maria@puntohealth.com Public Anna Muñoz Farré https://orcid.org/0009-0004-0250-287X Public Scientific

Health Foundry, 1 Royal Street

London United Kingdom SE1 7LL - anna@puntohealth.com Public Latha Velayudhan https://orcid.org/0000-0002-7712-930X Principal investigator

King’s College London and South London & Maudsley NHS Foundation Trust 16 De Crespigny Park

London United Kingdom SE5 8AB - latha.velayudhan@kcl.ac.uk Public Punto Health Ltd Industry Commercial National Institute for Health and Care Research http://dx.doi.org/10.13039/501100000272 47910134 true A school-based, two-armed individual-level randomised controlled trial evaluating the efficacy of the one-year adapted 'Becoming a Man' (BAM) cognitive-behavioural group intervention compared to business as usual school provision in reducing behavioural difficulties among adolescent boys aged 12 to 15 in mainstream secondary schools across London BAM UK 1. To evaluate if a one-year adapted school-based social and emotional learning program (BAM) reduces behavioral difficulties at post-intervention (T1) relative to BAU 2. To determine if the intervention reduces police arrests and offending behavior within 18 months following randomisation (T3) 3. To explore the mechanisms of change (self-regulation, emotional control, self-esteem) and their flow into medium-term school attendance and exclusion gains 4. To assess program feasibility, deliverability, and stakeholder acceptability during an internal pilot phase Background and study aims Violent and aggressive behaviours among young people present a significant challenge in our communities. These behaviours are often rooted in difficult life circumstances like poverty, trauma, or discrimination, where children develop 'automatic' defensive reactions as basic survival instincts. This study evaluates a program called 'Becoming a Man' (BAM) to support young men navigating these high-stress environments. BAM is a school-based program that helps boys develop self-control, emotional expression, and responsible decision-making. The aim of this study is to see if a one-year adapted version of the BAM program can effectively reduce behavioral difficulties and prevent boys from getting into trouble or being arrested. Who can participate? Participants are adolescent boys in Academic Years 8 to 10 (typically aged 12 to 15 years) attending participating mainstream secondary schools across Greater London. The program actively recruits a balanced mix of needs (15% thriving, 70% facing some challenges, and 15% in or approaching crisis) based on their risk of being involved in youth violence. Boys cannot participate if they are already in intensive counselling, plan to move away, have severe developmental delays, or have extreme absenteeism. What does the study involve? Referred boys who provide parent and personal consent are randomly assigned (by chance, like flipping a coin) into one of two groups. The treatment group receives the 'Becoming a Man' program. This consists of: weekly hour-long group sessions called 'BAM Circles' (27 total) held during school time; 6 after-school activities; brief informal check-ins; and one-to-one counselling support for those with higher needs. The control group receives normal school provision (known as 'Business as Usual'), which usually includes standard health and resilience classes (PSHE) and existing school services. All participating boys complete personal surveys at the start of the program, at the end of the school year, and 4 months later. The surveys measure things like self-esteem, self-control, emotional regulation, and behaviors. We also link study data to school records (to check attendance and exclusions) and local police records (to track arrests) for up to 1.5 to 2 years. What are the possible benefits and risks of participating? Participants in the BAM program may benefit from improved self-control, empathy, self-esteem, and social skills, which can lead to better school bonding and lower risks of exclusion. There are no major risks to participating. Some survey questions ask about sensitive topics (such as behavior or experiences of discrimination), which might make some boys feel uncomfortable. All surveys are private, completed with support from trained researchers, and boys can take breaks or skip questions whenever they want. Where is the study run from? The trial is run from the Ending Youth Violence Lab (the evaluator) in partnership with the London Borough of Islington (Young Islington Service, the delivery partner) and mainstream secondary schools in Greater London. When is the study starting and how long is it expected to run for? The study starts with a preparation phase in March 2026. Recruitment and delivery begin in mainstream schools in September 2026. The full evaluation (including long-term data collection from school and police records) will run until November 2030. Who is funding the study? The study is funded by the Youth Endowment Fund (YEF) in the United Kingdom. Who is the main contact? For more information about the study, please contact Lilli Wagstaff from the research team at lilli.wagstaff@bi.team Behavioural Difficulties (High-risk Subgroup - boys assessed at baseline as having upper-secondary or tertiary levels of need) Strengths and Difficulties Questionnaire (SDQ) - Self-Report Total Score (0–40, calculated by summing the conduct, hyperactivity, emotional, and peer subscales) T1 (Post-programme, approximately 9–10 months post-randomisation - main analysis point) Offending / Arrests (High-risk Subgroup - boys assessed at baseline as having upper-secondary or tertiary levels of need) administrative local police record linkage tracking a binary indicator of arrest (no arrests = 0, one or more arrests = 1), arrest counts, offence dates, offence types, and police-recorded outcomes T3 (18 months post-randomisation - main analysis point). Behavioural Difficulties (Full Cohort) Strengths and Difficulties Questionnaire (SDQ) - Self-Report Total Score (0–40, excluding the prosocial scale) T1 (Post-programme - main analysis point) Social Skills (Full Cohort) Strengths and Difficulties Questionnaire (SDQ) Prosocial subscale score (ranging from 0 to 10) T1 (Post-programme - main analysis point) Externalising Behaviours (Full Cohort): Strengths and Difficulties Questionnaire (SDQ) Externalising Problems scale (a combined score of the conduct and hyperactivity subscales, ranging from 0 to 20) T1 (Post-programme - main analysis point) Self-Esteem (Full Cohort) Rosenberg Self-Esteem Scale (RSES) - Self-report total score (ranging from 0 to 30, with higher scores indicating higher self-esteem) T1 (Post-programme - main analysis point) Self-Control and Emotional Regulation (Full Cohort) Difficulties in Emotion Regulation Scale (DERS) - Self-report total score (ranging from 36 to 180, where higher scores indicate greater emotional regulation difficulties) T1 (Post-programme - main analysis point) School Attendance (Full Cohort) School-level administrative attendance records to calculate percentage attendance T4 (21 months post-randomisation - main analysis point) School Exclusions, Suspensions, and Transfers (Full Cohort) School-level administrative records compiled into a combined binary indicator capturing whether a participant faced any exclusion, suspension, or school transfer (faced any event = 1, 0 otherwise) T4 (21 months post-randomisation - main analysis point) Offending (Full Cohort) Administrative local police record linkage tracking a binary indicator of arrest (no arrests = 0, one or more arrests = 1) T3 (18 months post-randomisation - main analysis point). Perceptions of Gender Norms and Stereotypes (Full Cohort) Global Early Adolescent Study Gender Stereotypical Traits Scale self-report total score T1 (Post-programme - main analysis point) Ethics approval required Ending Youth Violence Lab Independent Ethics Board

58 Victoria Embankment, Temple

London United Kingdom EC4Y 0DS 5 London Borough Islington Engagement & Research

222 Upper Street

London United Kingdom N1 1XR none 10.1186/ISRCTN47910134 Interventional Randomized controlled trial Open (masking not used) Active Parallel Prevention Treatment Not applicable 2030-12-31T00:00:00.000Z United Kingdom England London Borough of Islington

Young Islington Service, Children’s Services 222 Upper Street

London England N1 1XR false 1. Gender & Academic Year: Biological male in academic years 8 to 10 (aged 12 to 15 years) 2. Consent: Explicit written parental consent and young person assent for both intervention and evaluation (including data linkage and archiving) 3. School Setting: Attending participating mainstream secondary schools in Greater London. 4. Level of Need (at least one of the following tiers): - Lower Secondary Need: Flagged by staff as needing behavioral or wellbeing support, infrequent disruptive behavior, or temporary emotional academic dip - Upper Secondary Need: History of 1+ fixed-term exclusions, serious peer/behavioral conflicts, gang vulnerability/affiliation, substance misuse, criminal exploitation risk, or close family CJS involvement - Tertiary Need: Previous arrest with warning/caution, diversion/out-of-court disposal, or receiving Youth Offending Team (YOT) support Child 12 Years 15 Years Male 1080 0 1. Current Therapy: Already participating in intensive individual counselling, psychotherapy, or intense socio-emotional training outside the school setting 2. Planned Relocation: Planning to relocate outside of the local delivery area within the school year 3. Cognitive/Developmental Delay: Severe developmental delay which prevents active participation or ability to engage in abstract thinking 4. Absenteeism: Severe baseline chronic absenteeism in the previous school year (such that school attendance is practically non-existent) 5. Safety Risks: Actively homicidal 6. Clinical Crises: Actively suicidal or experiencing active psychosis 2026-09-03T00:00:00.000Z 2028-10-20T00:00:00.000Z Adolescent male social-emotional support needs, emotional dysregulation, behavioral difficulties (specifically conduct issues and hyperactivity), risk of school exclusion, and vulnerability to criminal justice involvement or youth violence. Mental and Behavioural Disorders Active Intervention Arm: Becoming a Man (BAM) 1-Year Adapted Curriculum Intervention & Curriculum: A selective, group-based social and emotional learning (SEL) intervention centering on six core values: Integrity, Accountability, Self-Determination, Positive Anger Expression, Respect for Womanhood, and Visionary Goal Setting. The traditionally two-year Chicago curriculum is condensed into a one-year model based on the 25-lesson London 'BAMual' manual. Delivery & Administration: Delivered in mainstream secondary schools by full-time, embedded, relatable male BAM Counsellors holding QCF-6 level qualifications. Delivery involves six primary activities: 1. BAM Circles: Structured weekly school-day group sessions of 8–12 participants 2. After-School Activities: Monthly sessions reinforcing each core value 3. Special Activities: Extra-curricular outings (e.g. affirmation trips, university visits, football league) 4. Brief Encounters: Informal, ad-hoc individual check-ins (<15 minutes) in hallways or playgrounds 5. 1-to-1 Support: Formally scheduled 30-minute counselling sessions for higher-need participants 6. Other Proactive Activities: In-school re-engagement and crisis support following suspensions or behavioral incidents Dosage: Delivered over one school year, including 27 one-hour BAM Circle sessions during the school day, 6 after-school value-consolidation sessions, and brief encounters targeted at once per month per participant Materials: The 25-lesson "BAMual" curriculum manual, boxing mitts, balls for group exercises, video education (such as Jordan to the Max), and emoji cards for reflection Control Comparator Arm: Business as Usual (BAU) Comparison: Control group participants receive standard school services to serve as a comparator How it is administered: Delivered by regular school staff or existing school partners Content: Support is typically based on the statutory Personal, Social, Health and Economic (PSHE) education curriculum. It is delivered through discrete lessons, assemblies, and external partnerships with support organizations (such as Football Beyond Borders, Kooth, or Place2Be) designed to equip students with resilience and modern life skills. Randomisation approach: This is a two-arm, parallel-group randomised controlled trial comprising an internal pilot followed by an efficacy phase. Eligible participants are individually randomised (1:1) to either the BAM intervention group or the BAU control group. Participants are randomised at the individual student level, stratified by school and baseline Holistic Student Assessment (HSA) tiers to guarantee balanced group dynamics and facilitate mixed-tier delivery. Randomisation and allocation to groups is programmatically executed by the independent research team at the Ending Youth Violence Lab using a random number generator in Stata, linked to each young person's Unique Pupil Number (UPN). Data collection approach: All participants (active and control arms) are tracked across several key data collection points: 1. Surveys: Validated self-report survey measures are completed by participants in groups in person at baseline (prior to randomisation), post-programme (approximately 9 to 10 months post-randomisation), and at a 4-month follow-up (approximately 13 months post-randomisation). 2. Local Police Records: Administrative local police arrest data is securely linked and analyzed to track offending outcomes at 18 months post-randomisation. 3. School Records: School-level administrative data is extracted to assess percentage attendance and a combined binary indicator of exclusions, suspensions, and school transfers at 21 months post-randomisation. Behavioural De-identified individual participant-level data generated and analysed during this study will be securely stored and archived in the Youth Endowment Fund (YEF) data archive, in line with ethical approvals, UK data protection legislation, and YEF data governance requirements. The YEF archive is hosted within the Office for National Statistics (ONS) Secure Research Service (SRS). Identifying information is removed or pseudonymised prior to archiving, and data are stored in separate datasets to prevent direct identification of participants. Access to data held in the YEF archive will be available only to approved researchers via the ONS Secure Research Service, following review and approval through the YEF’s data access processes. Researchers must be ONS-accredited and demonstrate that proposed analyses are scientifically appropriate, ethically approved, and in the public interest. All outputs are subject to disclosure control checks prior to release. Data will become available following publication of the main study findings and will be retained in the YEF archive for long-term research and archiving purposes, in accordance with YEF retention policies and periodic review. Available on request Stored in non-publicly available repository Protocol

1e28e948-ee80-43b8-9c49-bb5ba95ba4d2 9176a9a3-c3da-4741-a248-dcc83823275e d2cb298f-d53a-4008-ab59-576ae10ce001 9cf44355-af77-41e3-8e39-1a70a78cb013 Yes Protocol file 50206 BAM efficacy trial protocol V4.pdf 3baffbc6-4662-48dd-b699-773c36167440 true application/pdf 2157138 9f7efcf0aed3bbbf96df7ec49541bfca Tom McBride https://orcid.org/0009-0003-0660-5035 Principal investigator

Behavioural Insights Team, 58 Victoria Embankment, Temple

London United Kingdom EC4Y 0DS +44 7745116083 tom.mcbride@bi.team Public Lilli Wagstaff https://orcid.org/0009-0005-9194-5118 Public Scientific

Behavioural Insights Team, 58 Victoria Embankment, Temple

London United Kingdom EC4Y 0DS +44 7745116083 lilli.wagstaff@bi.team Public The Behavioural Insights Team https://ror.org/03mk5b468 Non-commercial Youth Endowment Fund http://dx.doi.org/10.13039/501100024398 98883107 true TBI-REPORTER prospective proof of principle study 3P Study The 3P TBI reporter study aims to: 1. Establish the feasibility of a standardised, national TBI (Traumatic Brain Injury, Head Injury) reporting network 2. Refine a core data and biosample collection protocol for acute and chronic TBI studies to be further utilised across the TBI REPORTER platform 3. Evaluate the clinical feasibility of the TBI REPORTER data repository 4. Provide pilot data for sample size calculation in future EMN studies Background and study aims Traumatic brain injury (TBI) affects millions of people worldwide and can have long-lasting effects on physical health, thinking, emotions, and quality of life. However, doctors and researchers still do not fully understand why people recover differently after similar injuries. Better information is needed to improve diagnosis, predict recovery, and develop more effective treatments for future patients. The 3P Study is part of the UK TBI-REPORTER programme, a national research initiative designed to improve understanding of traumatic brain injury. The study aims to test whether researchers across hospitals in the UK can collect information in a consistent way from people with different types and severities of TBI. Researchers will collect information from medical records, brain scans, blood and other biological samples, brain activity recordings, and follow-up assessments of recovery. The information gathered will be used to create a national research resource that will support future studies and help improve the care and outcomes of people living with traumatic brain injury. Who can participate? Adults diagnosed with a traumatic brain injury who receive care at a participating hospital. What does the study involve? Participants will be asked to allow researchers to collect information about their injury and treatment, provide blood samples, take part in follow-up assessments, and may also be invited to have brain scans and brain activity tests. What are the possible benefits and risks of participating? Taking part is unlikely to benefit participants directly, but the information collected may help improve understanding, diagnosis and treatment of traumatic brain injury for future patients. Risks are low but may include discomfort or bruising from blood samples, inconvenience from study visits, and possible discomfort during MRI scans or other assessments. Where is the study run from? University of Cambridge, UK. When is the study starting and how long is it expected to run for? The study started in June 2025 and is expected to finish in March 2029. Who is funding the study? UK Research and Innovation (UKRI) Medical Research Council, UK. Who is the main contact? Joanne Outtrim, TBI-REPORTER@medschl.cam.ac.uk Feasibility of recruitment and retention from enrolment to study completion (up to 24 months) data collected from study records on participant recruitment and retention rates the end of the study Feasibility of standardised data collection up to 24 months data collected from study records on the completion of clinical, biosample, MRI, EEG and outcome assessment datasets at recruitment and scheduled follow-up visits the end of the study Characterize TBI and identify endotypes for interventional studies data on clinical features, neuroimaging, and blood biomarkers ? Functional outcome the Glasgow Outcome Scale Extended (GOSE) scheduled follow-up assessments [?] Health-related quality of life the EQ-5D and Quality of Life After Traumatic Brain Injury Overall Scale (QOLIBRI-OS) scheduled follow-up assessments [?] Cognitive function the Cognitron cognitive assessment platform ? Ethics approval required East of England - Cambridge Central Research Ethics Committee

2 Redman Place, Stratford

London United Kingdom E20 1JQ 25/EE/0055 10.1186/ISRCTN98883107 351717 CPMS: 66498, MR/Y008502/1 351717 66498 MR/Y008502/1 Observational Cohort study Treatment 2029-03-01T00:00:00.000Z United Kingdom England Scotland Addenbrookes Hospital

Hills Road

Cambridge England CB2 0QQ E7D9E@2.16.840.1.113883.2.1.3.2.4.18.48 St. Marys Hospital

Praed Street

London England W2 1NY Kings College Hospital

Denmark Hill

London England SE5 9RS V07373@2.16.840.1.113883.2.1.3.2.4.18.48 Royal Infirmary of Edinburgh at Little France

51 Little France Crescent Old Dalkeith Road Edinburgh

Lothian Scotland EH16 4SA S314H@2.16.840.1.113883.2.1.3.8.2.16.2 Queen Elizabeth University Hospital

1345 Govan Road

Glasgow Scotland G51 4TF G405H@2.16.840.1.113883.2.1.3.8.2.16.2 true 3P acute cohort inclusion criteria: 1. Clinical diagnosis of TBI 2. Consideration for CT scan based on NICE screening criteria 3. Presentation within 24 hours of injury 4. Informed consent/consultee agreement obtained according to local and national requirements 5. > = 18 years of age 3P chronic cohort inclusion criteria: 1. Clinical diagnosis of TBI 2. Consideration for CT scan based on NICE screening criteria 3. > = 6 months after TBI 4. Informed consent obtained according to local and national requirements 5. > = 18 years of age 6. Able to engage with biosample, MRI and outcome assessments Healthy volunteer inclusion criteria: 1. > = 18 years of age 2. Informed consent agreement received Mixed 18 Years 120 Years All 450 0 3P acute cohort exclusion criteria: The following will be assessed on a case-by-case basis: 1. Severe pre-existing neurological disorder that would confound outcome assessments. In practical terms, this would exclude individuals who, because of a neurological disease, would be assessed as having pre-injury moderate disability (or worse) on the Glasgow Outcome Score (GOSE < 6). 2. Patients who may have difficulties in understanding written or verbal information in English that would limit their ability to consent and complete the outcome assessments. 3. Patients who have a catastrophic injury where death is expected within 24 hours of injury. Chronic cohort exclusion criteria: The following will be assessed on a case-by-case basis: 1. Severe pre-existing neurological disorder that would confound outcome assessments. In practical terms, this would exclude individuals who, because of a neurological disease, would be assessed as having pre-injury moderate disability (or worse) on the Glasgow Outcome Score (GOSE < 6). 2. Patients who have difficulties in understanding written or verbal information in English that would limit their ability to consent and complete the outcome assessments. Healthy volunteer exclusion criteria: 1. Significant neurological or systemic disease (American Society of Anaesthesiologists Grade 1 or 2) 2. History of TBI requiring hospital attendance or medical input 2025-06-12T00:00:00.000Z 2029-03-01T00:00:00.000Z Injuries to the head Injury, Occupational Diseases, Poisoning The 3P study is a prospective observational study that will recruit up to 350 TBI patients across all severity levels at 7 sites over 24 months. Patients will be enrolled upon hospital presentation (ED, ward, ICU and clinic) and followed for up to 2 years to track their recovery from acute injury onward. The 3P data collection will be divided into five groups based on clinical care pathways at enrolment: - ED cohort: patients evaluated in the ED and discharged (n=100) - Ward cohort: patients admitted to the hospital but not to ICU (n=100) - ICU cohort: patients admitted directly from the ED or other hospital to the ICU (n=100) - Chronic cohort: patients presenting more than 6 months after initial TBI (up to 50) - Healthy volunteers: volunteer subjects at each centre for MR study (up to 100) All patients will be screened for eligibility before informed consent is obtained. In the case of patients who are assessed as not having capacity, a consultee/proxy will be approached as set out in the Mental Capacity Act 2005/Adults with Incapacity (Scotland) Act 2000. There are core data modules to which patients can take part, although some parts of the study may not be available depending on local resources. The 3P baseline data clinical variables will be prospectively collected from all enrolled patients, through medical records and personal interviews, and will include, for example: • Demographic information • Socioeconomic information • Medical history • Mechanism of injury • Pre-hospital clinical course variables • Brain CT report • Emergency department clinical course • Hospital admission clinical course • Hospital therapies, surgeries and neuromonitoring • Admission and discharge information • Acute care outcome evaluation • Biomarker samples • 12-lead ECG and rhythm strip The 3P study will collect bodily fluid samples (blood, CSF, urine, and faeces) to identify substances that may influence the body's response to and recovery from TBI. Centres in the MR data collection arm will use 3 Tesla scanners for MR brain scans. Some will perform ultra-early scans within 72 hours of TBI, while others will scan within 5 days, aiming to scan all patients within 2-3 weeks. Each participant will typically have two MRIs: one during the acute stage and one at follow-up (6, 12, or 24 months). Chronic cohort participants may have up to four MRIs over 24 months. Patients may be invited for follow-up visits over 2 years, including blood sampling, neurocognitive tests, and quality-of-life questionnaires at various time points. At sites with MRI and EEG facilities, additional MRI scans and EEG tests may be done. The length of visits will vary, as some tasks, like questionnaires and cognitive tests, can be completed online or by phone. Other De-identified data generated and/or analysed during this study will be made available through the Dementias Platform UK (DPUK) Data Portal (https://portal.dementiasplatform.uk/), subject to relevant approvals and governance requirements. Approved researchers from academic, healthcare, governmental, or commercial institutions will be able to access the data through the secure DPUK/TBI-REPORTER Trusted Research Environment for scientifically and ethically approved research purposes. Data will be made available following study completion and publication of primary findings and will remain available in accordance with repository policies. Only de-identified data will be shared, with access governed by participant consent, ethical approvals, data protection legislation, and applicable data access agreements. Stored in publicly available repository

e88af827-040a-412d-a108-c4ae0cd645b7 3837d217-fb54-42e8-a6b7-c9d95d26b9ec 2e1e3d7b-f494-44c8-8cb4-a9776a0467f7 Yes TBI-REPORTER Study team - Principal investigator Scientific Public

University of Cambridge, Box 93, Department of Medicine, Addenbrooke’s Hospital, Hills Road

Cambridge United Kingdom CB2 0QQ +44 (0)1223 330758 TBI-REPORTER@medschl.cam.ac.uk Public Cambridge University Hospitals NHS Foundation Trust Hospital/treatment centre https://ror.org/04v54gj93 Non-commercial Medical Research Council http://dx.doi.org/10.13039/501100000265 78297159 true Yaba Guy Che (For the men): Implementation and evaluation of a co-developed multi-disease intervention for men The primary objective of this Hybrid Type 2 effectiveness-implementation study is to measure the feasibility and impact of a community-based, digitally supported, integrated health intervention on knowledge of HIV status, ART coverage and viral load suppression among MLHIV, and uptake of hypertension screening services among men aged ≥18 years in an urban community in Lusaka, Zambia. Other objectives are: 1. To measure the impact of the Yaba Guy Che intervention on: 1.1. Uptake of STI testing 1.2. Uptake of TB screening 1.3. Uptake of diabetes screening 1.4. Knowledge of hypertension 1.5. Use of effective HIV prevention methods among men not living with HIV 2. To evaluate the implementation of the Yaba Guy Che intervention using Proctor’s implementation outcomes framework, including adoption, reach, fidelity, acceptability, sustainability, and cost (related to scalability). We will further examine reach of the intervention by conducting one case-control study to examine factors related to men’s attendance at the YGC spaces and PrEP use among eligible men, and examine factors related to access to and use of the digital health pathways 3. To evaluate a peer monitoring group as a community accountability mechanism, and to document men’s experiences of accessing and engaging with the Yaba Guy Che intervention and care pathway 4. To assess the costs, cost-effectiveness, equity impact and financial sustainability of the Yaba Guy Che intervention at scale Background and study aims Many men find it difficult to use health services because of concerns about privacy, long waiting times, inconvenient opening hours, stigma, or because health facilities may not feel welcoming to them. As a result, some men may miss opportunities for testing, screening, prevention, and treatment. The Yaba Guy Che (For the Men) study aims to find out whether a new community-based health programme can improve men's access to a range of health services in Lusaka, Zambia. The programme combines face-to-face services with digital tools and focuses on HIV, sexually transmitted infections (STIs), tuberculosis (TB), high blood pressure, and diabetes. Researchers will assess whether the programme increases HIV testing, HIV treatment coverage, viral load suppression among men living with HIV, and uptake of high blood pressure screening. The study will also explore how acceptable, practical, cost-effective, and sustainable the programme is. Who can participate? Men can take part if they: 1. Are aged 18 years or older 2. Live, work, or regularly spend time in the study community in Lusaka, Zambia 3. Are willing and able to provide informed consent What does the study involve? Participants will have access to a package of health services designed specifically for men. The programme includes: 1. A Prevention Points Card that gives participants a unique identification number and records the services they use 2. Community-based spaces where men can access HIV, STI, TB, and non-communicable disease services in one location 3. Digital health services, including vending machines that provide HIV self-testing kits and STI self-sampling kits, as well as mobile phone-based services for receiving results and health information Researchers will collect information about participants' health service use. This may include questionnaires, HIV testing, blood tests for viral load among men living with HIV, and questions about screening for conditions such as high blood pressure, TB, STIs, and diabetes. What are the possible benefits and risks of participating? Possible benefits include easier access to a range of health services in one place, greater access to health information, opportunities for testing and screening, and earlier identification of health conditions that may need treatment or follow-up care. Possible risks may include discomfort when answering personal health questions, concerns about privacy when discussing health issues, and minor discomfort from blood sample collection where this is required. The research team will take steps to protect participants' confidentiality and ensure that participation is voluntary. Where is the study run from? The study is being carried out in urban communities in Lusaka, Zambia. It is led by Zambart in collaboration with the London School of Hygiene & Tropical Medicine. When is the study starting and how long is it expected to run for? The study is expected to start recruiting participants in September 2026. Recruitment is planned to continue until September 2029, with the study due to finish in September 2029. Who is funding the study? The study is funded by the National Institute for Health and Care Research (NIHR), United Kingdom. Who is the main contact? Dr Mwelwa Phiri, Mwelwa@zambart.org Knowledge of HIV status (defined as having tested for HIV in the last 12 months and receiving a negative result, or self-reporting living with HIV) self-report questionnaire and rapid HIV testing baseline and endline ART coverage among MLHIV self-report questionnaire baseline and endline Viral load suppression among MLHIV blood sample based viral load testing baseline and endline Uptake of hypertension screening services self-report questionnaire baseline and endline uptake of STI testing self-report questionnaire baseline and endline uptake of TB screening services self-report questionnaire baseline and endline Knowledge of hypertension self-report questionnaire baseline and endline uptake of diabetes screening services self-report questionnaire baseline and endline Use of at least one effective HIV prevention method among men not living with HIV self-report questionnaire baseline and endline Ethics approval required Observational / Interventions Research Ethics Committee, London School of Hygiene and Tropical Medicine,

London School of Hygiene & Tropical Medicine Keppel Street London WC1E 7HT

London United Kingdom WC1E 7HT 33790 10.1186/ISRCTN78297159 Interventional N/A: single arm study Open (masking not used) Uncontrolled Single Device feasibility Health services research Prevention Screening Supportive care Treatment Not applicable 2029-09-30T00:00:00.000Z Zambia true 1. Aged over 18 years old at the time of enrolment 2. Reside in, work in, or regularly spend time in study community 3. Able and willing to provide informed consent Adult 18 Years 60 Years Male 45000 0 Anything that, in the opinion of the investigator, would preclude a man from providing voluntary informed consent, such as intoxication, acute physical or mental illness, other that would make study participation unsafe (for example, aggressive behaviour, or other safety concerns for the man or for the team), complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives. 2026-09-14T00:00:00.000Z 2029-09-30T00:00:00.000Z Prevention of HIV, TB, STIs and Non-Communicable diseases Infections and Infestations The Yaba Guy Che intervention will deliver an integrated package of HIV, STI, NCD, and TB services through a community-based platform designed specifically for men, combined with a digitally supported care pathway. The intervention aims to address barriers that prevent men from accessing facility-based services including lack of privacy and confidentiality, inconvenient operating hours that conflict with work schedules, perception of health facilities as "women's spaces," fear of stigma, and long waiting times. Integration is a fundamental design principle, allowing men to access multiple services in a single visit rather than requiring separate appointments for different health needs, thereby reducing the time burden of health-seeking and normalising healthcare as part of comprehensive well-being rather than signalling specific stigmatised conditions. The intervention consists of three core components: 1. A Prevention Points Card (PPC) system that provides a unique ID and tracks service utilization (and may incentivize, by providing rewards such as soap, toothpaste, etc, service uptake if agreed upon with Community Advisory Boards and the Peer Monitoring Group) 2. Community-based service delivery spaces providing comprehensive HIV, STI, NCD, and TB services 3. A digital health pathway that includes vending machines dispensing HIV self-testing and STI self-sampling kits, and mHealth for results access and health information The total duration of the intervention is approximately 24 months, there will be no follow up beyond the intervention. Other Data sharing statement to be made available at a later date 6e4f9bed-3c54-4668-9d6f-5158e574f7f9 6b796ddc-f47d-4f56-9c5f-55e804d1213b e44dc2a9-46fd-4dff-9d39-8649aaa1df43 b9107887-19a2-4769-b387-0c1aef96c43b No Helen Ayles https://orcid.org/0000-0003-4108-2842 Principal investigator Scientific

Zambart House, Unza Ridgeway Campus Off Nationalist Road

Lusaka Zambia P.O Box 50697 +260 211254710 Helen@zambart.org.zm Public Mwelwa Phiri https://orcid.org/0000-0001-6029-9372 Public Principal investigator

Zambart House, Unza Ridgeway Campus Off Nationalist Road

Lusaka Zambia P.O Box 50697 +260 211254710 Mwelwa@zambart.org Public London School of Hygiene & Tropical Medicine https://ror.org/00a0jsq62 Non-commercial National Institute for Health and Care Research http://dx.doi.org/10.13039/501100000272 12843033 true Exploring patients’ experiences of mealtime support in an adult inpatient eating disorder unit The primary aim of this project is to explore the experiences of patients during mealtimes within an adult eating disorder unit. By examining these experiences in depth, the overarching goal is to uncover critical insights that can inform improvements in the mealtime environment, ultimately enhancing the quality of care provided within the unit and enhancing recovery. Background and study aims Mealtimes are an important part of treatment and recovery for people with eating disorders receiving inpatient care. Understanding patients’ experiences of mealtime support may help identify ways to improve the mealtime environment and the quality of care provided. This study aims to explore patients’ experiences of mealtimes within an adult eating disorder unit. The findings will be used to identify recommendations that could help improve mealtime support and enhance recovery for future patients. Who can participate? Adults aged 18 years and over who are current inpatients on Iris Ward at St Ann's Eating Disorder Service, or patients attending the Day Programme who were discharged from Iris Ward within the previous three months, and who have a diagnosis of anorexia nervosa. What does the study involve? Participants will be invited to take part in either: - An individual interview - A focus group Participants can choose which option they would prefer. Interviews and focus groups will last approximately 50 minutes and will use a set of open-ended questions to explore experiences of mealtimes and mealtime support within the eating disorder service. Researchers will analyse the discussions to identify common themes and experiences. What are the possible benefits and risks of participating? Participants may not receive a direct benefit from taking part. However, the information collected may help improve mealtime support and the quality of care provided within eating disorder services in the future. Some participants may find discussing their experiences upsetting or emotionally challenging. Appropriate support will be available if needed. Where is the study run from? Iris Ward, St Ann's Eating Disorder Service, North London NHS Foundation Trust, London, UK. When is the study starting and how long is it expected to run for? October 2025 to June 2026. Who is funding the study? North London NHS Foundation Trust, UK. Who is the main contact? Mr Ashton Dublin, ashton.dublin@nhs.net. Patient experiences of mealtimes data collected during individual interviews/focus groups one time point Ethics approval required HRA and Health and Care Research Wales (HCRW)

Office for Research Ethics Committees Northern Ireland (ORECNI), Lissue Industrial Estate West, 5 Rathdown Walk

Lisburn United Kingdom BT28 2RF 25/NI/0080 10.1186/ISRCTN12843033 345514 D-611-2653 345514 D-611-2653 Qualitative methodology of individual interviews/focus groups Observational Cross sectional study Treatment 2026-06-26T00:00:00.000Z United Kingdom England Iris Ward, St Ann's Eating Disorder Service

North London NHS Foundation Trust St Ann's Hospital St Ann's Road Tottenham

London England N15 3TH Patient false 1. Must be a current inpatient on Iris Ward at St Ann's Eating Disorder Service OR 2. Be a current patient on the Day Programme at St Ann's Eating Disorder Service and have been discharged from Iris Ward within the last 3 months 3. Must be diagnosed with Anorexia Nervosa or Anorexia Nervosa Unspecified according to ICD-11 criteria 4. Participants must have the capacity to take part in the research project Mixed 18 Years 75 Years All 25 8 1. If the individual is being enterally fed during the course of the research 2. If the individual is in a high level of distress or at high risk of self-harm 3. If the individual is only being seen at St Ann's Eating Disorder Service as an outpatient 4. Individuals with a diagnosis of ARFID (Avoidant/Restrictive Food Intake Disorder) 5. If the individual has an active comorbid mental health condition (e.g., psychosis, severe depression) that would have a significant impact on their experience of mealtimes, not including personality disorder 5. If the individual has a severe learning disability 6. If the individual is pregnant 7. If the individual has unmanaged diabetes and/or uses insulin as a compensatory behaviour 8. If the individual has active problematic substance misuse 2025-10-27T00:00:00.000Z 2026-05-01T00:00:00.000Z Anorexia Nervosa, Eating Disorders Mental and Behavioural Disorders This study will use a qualitative methodology of individual interviews/focus groups to explore patient experiences of mealtimes. Participants will be able to request either an interview or a focus group, based on their personal preference. Both interviews and focus groups will follow the same semi-structured interview schedule. Interviews/focus groups will last around 50 minutes. Thematic analysis will be utilised to analyse the interview transcripts and focus group discussions. Thematic analysis is a systematic approach to identifying patterns, themes, and categories within qualitative data. By systematically coding and analysing the data, the study aims to identify recurring themes and patterns related to mealtime experiences, facilitating a deeper understanding of the factors involved. The study will collect data for up to 6 months post-enrolment, and a further 12-month period is planned for data analysis. All researchers will have valid DBS checks as part of their NHS employment. The data collection site is part of the North London NHS Foundation Trust. Participants will be recruited from the inpatient ward and day programme of St Ann’s Eating Disorder Service (SAEDS). In total, we will aim to recruit up to 25 participants. Other Not expected to be made available

ac80fe7c-2c14-459d-be5b-fbfd3b4a52da b79a6846-6deb-45e3-8016-0c71c0f70365 925a6c71-bfba-40d6-a348-353a1079f935 8e82c569-6e7a-4d99-810b-4e5c53a39ebc No Participant information sheet 49878_PIS_v1.0_08April2025.pdf 8f90cbaf-2063-4723-88cc-1a398f1f70b1 true application/pdf 268766 23bcb67aef4e9f5830e9e5a72bc48eb1 Ashton Dublin Principal investigator

St Ann's Eating Disorder Service North London NHS Foundation Trust Plum Block D St Ann's Hospital, St Ann's Road Tottenham

London United Kingdom N15 3TH +44 0208 7026240 ashton.dublin@nhs.net Public Julie Evans https://orcid.org/0009-0008-3629-334X Scientific Public

St Ann's Eating Disorder Service North London NHS Foundation Trust Plum Block D St Ann's Hospital, St Ann's Road Tottenham

London United Kingdom N15 3TH +44 0208 7026240 julie.evans46@nhs.net Public North London NHS Foundation Trust Hospital/treatment centre Non-commercial North London NHS Foundation Trust 82732915 true PuntoTest: speech-based AI cognitive screening in NHS primary and secondary care PuntoTest Primary Objective To assess the feasibility of implementing PuntoTest within NHS primary and secondary care settings. This includes: 1. The ability to recruit the target number of participants across sites 2. Participant completion rates of the PuntoTest assessment 3. The feasibility of recruitment pathways from both primary and secondary care Secondary Objectives 1. To compare performance of PuntoTest with current gold standard cognitive assessment, ACE-III (Addenbrooke's Cognitive Examination-III) and further develop the model. 2. To assess variation in performance across demographic groups, including age, sex, and education 3. To explore participant experience and acceptability of the PuntoTest assessment through qualitative interviews 4. To generate preliminary health economics data to inform future NHS commissioning decisions and grant applications Background and study aims Nearly one million people in the UK have dementia, but only about two-thirds have been formally diagnosed. Early detection of memory problems is difficult in routine practice, and waiting times for specialist assessment are often very long — often exceeding 13 weeks when the recommended benchmark is 6 weeks. This puts pressure on NHS memory services, and delays care. PuntoTest is a simple speech-based tool using artificial intelligence to screen for memory problems. It can be used by patients themselves or with support from a clinician, offering a flexible and accessible approach to early detection. The tool has already been tested in other countries with promising results. This study tests whether it works well in NHS memory clinics and GP practices, and whether it's practical to use in the UK. Who can participate? Patients aged 50 years or over who have concerns about their memory, mild memory problems, mild dementia, or no memory concerns (as a healthy comparison volunteer) and have had a recent memory assessment (ACE-III within the last 3 months), or can do this as part of the study What does the study involve? The study involves a single visit lasting about 30 minutes. Participants will answer a few basic questions about themselves at the start, then speak into a tablet to complete a simple memory screening tool, and also take a standard memory test (ACE-III) so we can compare results. No additional visits needed. What are the possible benefits and risks of participating? Benefits: Participation will help us understand whether PuntoTest could support earlier and more accurate memory assessments in the NHS. This could benefit many people with memory concerns in the future and help improve the way care is delivered. Taking part may not directly benefit participants personally. However, the ACE-III assessment, which is completed during the same visit, is already part of the standard care. Risks: Minimal. There are no known medical risks associated with taking part. The assessment involves speaking into a tablet and completing a standard memory test. Both are low-risk activities. Some people may find a memory assessment slightly tiring or stressful, or may feel worried about the results. If participants find it difficult at any point, they can speak to the research team. Participants are free to stop at any time. Where is the study run from? The study is sponsored by PuntoHealth Ltd and conducted across four NHS sites in England. When is the study starting and how long is it expected to run for? The study is expected to start in September 2026, depending on site setup. Enrolment of participants is planned over approximately 12 months (from September 2026 to July 2027). Data analysis is anticipated to be completed by December 2027, although this date is indicative and may change depending on recruitment progress and data collection completion. Who is funding the study? 1. The National Institute for Health and Care Research (NIHR) Invention for Innovation (i4i) FAST Programme. 2. The UK Science and Technology Facilities Council (STFC)-UK Research and Innovation (UKRI). Who is the main contact? Maria Rollano Corroto, Project Manager, PuntoHealth Ltd, maria@puntohealth.com Feasibility Measure: Recruitment rate participant enrolment data collection at each site, calculated monthly time points and at the end of the recruitment period Feasibility Measure: PuntoTest assessment completion rate study database records, calculated as the proportion completing assessments, the end of the study Feasibility Measure: Recruitment pathway distribution enrolment data, comparing the proportion recruited via primary vs secondary care, the end of recruitment PuntoTest performance exploratory comparison of PuntoTest outputs with ACE-III scores a baseline assessment, analysed at the end of data collection Demographic variation in PuntoTest outputs subgroup analysis by age, sex, education, and living status across all participants, analysed the end of data collection Participant acceptability qualitative thematic analysis of interviews conducted post-assessment (optional interviews with ~15 participants), analysed study completion Health Economics: Healthcare resource use, service activity, and staff time associated with PuntoTest implementation data collection on time to assessment, clinical staff involvement, and activities, analysed the end of data collection Health Economics: Service capacity indicators, including time to assessment and triage activity/duration service activity data, analysed the end of data collection Health Economics: Implementation and staff-related costs associated with PuntoTest introduction cost data collection, analysed the end of data collection Health Economics: Health economic evaluation data for PuntoTest to inform future NHS economic evaluation resource use analysis, analysed study completion Ethics approval required London - Stanmore Research Ethics Committee

2 Redman Place, Stratford

London United Kingdom E20 1JQ 26/LO/0440 10.1186/ISRCTN82732915 354094 CPMS: 72001, NIHR: 510914, NHSPOC01 354094 72001 510914 NHSPOC01 Interventional Non-randomized controlled trial Open (masking not used) Active Single Screening Not applicable 2027-12-17T00:00:00.000Z United Kingdom England OXLEAS NHS Foundation Trust — Greenwich Memory Service

Memorial Hospital, Shooters Hill, Woolwich

London England SE18 3RG RPG@2.16.840.1.113883.2.1.3.2.4.18.48 North London NHS Foundation Trust — Enfield Memory Service (EMS)

Chase Farm Hospital, The Ridgeway, Enfield

London England EN2 8JL South London and Maudsley NHS Foundation Trust — Lewisham Memory Service

91 Granville Park, Lewisham

London England SE13 7DW Y7O8M@2.16.840.1.113883.2.1.3.2.4.18.48 Gallions Reach Health Centre

Bentham Road

London England SE28 8BE G83012@2.16.840.1.113883.2.1.3.2.4.18.48 true 1. Adults aged > = 50 years 2. Capacity to provide informed consent 3. Individuals in one of the following groups, as determined through routine clinical assessment and application of the following criteria: 3.1. Subjective Cognitive Decline (SCD; also referred to as Subjective Memory Complaints, SMC). The following criteria will be used to define SCD (Jessen et al., 2014): 3.1.1. Self-experienced persistent decline in cognitive capacity compared with a previously normal status 3.1.2. Normal performance on standardised cognitive assessments 3.1.3. No significant impairment in activities of daily living 3.1.4. Absence of mild cognitive impairment or dementia 3.2. Mild Cognitive Impairment (MCI). An individual meeting the following diagnostic criteria will be identified as having MCI (Albert et al., 2011): 3.2.1. Concern regarding a change in cognition, whether reported by the self, informant, or clinician. 3.2.2. Objective evidence of impairment in one or more cognitive domains, typically including memory. 3.2.3. Preservation of independence in functional abilities. 3.2.4. Absence of dementia. 4. Mild dementia. An individual meeting the following diagnostic criteria will be identified as having mild dementia (DSM-5, 2013): 4.1. Evidence of cognitive decline from a previous level of performance, reported by the individual, an informant, or a clinician 4.2. Objective impairment in one or more cognitive domains (e.g. memory, attention, language, executive function) 4.3. Interference with independence in everyday activities (e.g. requiring assistance with complex tasks) 4.4. Not better explained by delirium or another mental disorder 5. Healthy controls. An individual meeting the following diagnostic criteria will be identified as a healthy control: 5.1. No self-reported cognitive concerns 5.2. Normal performance on a standardised cognitive assessment, defined as a score of > = 27 on the Mini-Mental State Examination (MMSE) (Molloy & Standish, 1997\) 5.3. No clinical diagnosis of mild cognitive impairment or dementia 5.4. Independent in activities of daily living 6. Availability of a recent ACE-III assessment (within the previous 3 months), or ability to complete the assessment as part of the study procedures 7. Sufficient proficiency in English to complete the study procedures and digital assessment Mixed 50 Years 120 Years All 150 0 1. Moderate or severe dementia, or any condition associated with lack of capacity to provide informed consent 2. Inability to complete the ACE-III assessment required for study participation 3. Severe sensory, motor, or cognitive impairments that would prevent completion of the study procedures, including use of the digital assessment tools, even with support 4. Acute or unstable physical or mental health conditions that, in the opinion of the clinical team, would make participation inappropriate 2026-09-28T00:00:00.000Z 2027-07-31T00:00:00.000Z Early detection of memory problems Nervous System Diseases Study Design This is a multi-site feasibility study designed to assess the implementation of PuntoTest within NHS primary and secondary care settings. This includes embedded health economic assessments, as well as exploratory evaluation of performance against the current gold standard. What Happens to Participants Eligible participants are identified by clinical staff at each site as part of their routine care pathway. The Patient Information Sheet (PIS) is provided in advance by the treating clinician or GP, allowing participants at least 24 hours to consider participation and ask questions. If they are interested, a study visit is arranged, where a trained member of the research team will explain the study and obtain written informed consent prior to any study procedures. At the clinic or GP visit: 1. The research nurse answers any questions and takes written informed consent (15-30 minutes). 2. The participant completes the 10-minute PuntoTest assessment on an iPad in the clinic room, which includes a brief collection of demographic information (such as age, sex, and education level) followed by the speech-based assessment. 3. The standard ACE-III assessment will then be administered by the clinician as part of routine care. No additional appointments are required. At the GP site (Greenwich), Dr James Rogers will be trained in ACE-III administration for this study. 4. A subset of participants will be invited to take part in a qualitative interview, either in the form of an individual interview or a focus group. These will be conducted by a qualitative PPIE expert from UCLP. Depending on the number of participants who opt in to participate. These will be delivered by either video call or in person, to explore their experience of using PuntoTest. They will be compensated £25 per hour for this additional optional qualitative component. Number of Participants and Sites - NHS participants: approximately 150 (spread across Oxleas Memory Service, Enfield Memory Service, Lewisham Memory Service, and Greenwich GP Practice) Patient and Public Involvement A lived experience advisory panel were involved in the review of the protocol and patient consent materials, as part of a series of PPIE workshops led by UCLPartners. Select members from this panel will also be invited to sit on the Steering Committee. Co-design workshops will be held during study delivery to inform ongoing participant engagement and materials. Device Not Applicable PuntoTest Data sharing statement to be made available at a later date Protocol

31ade945-28cd-4a05-9a57-8ce95501f1f6 76e45976-a163-48f1-8abc-ce3042db84a4 3fd086be-7980-4a6a-a652-04cb2001eec0 ee70541c-c9b3-43be-a36b-bba1ac36a477 58e9944d-077c-4d9f-a36f-b26e7140a43e b9a2826d-60af-48fe-b2f7-4dd2447f6dee b4d599e3-28bb-459b-b65c-d9246dfbaccc 121d1aab-3afb-48de-9fac-e26ed4620f68 No Protocol file ISRCTN82732915 _Protocol_v2.0_17Jun2026.pdf 8d14d9c1-df56-4a82-bd72-f3f70d87613e true application/pdf 888091 84d4cd4e5cf5cff2ee2dc2e5a6391f31 Maria Rollano Corroto https://orcid.org/0009-0005-8185-4474 Scientific Public

Project Manager, Punto Health Ltd Health Foundry, 1 Royal Street

London United Kingdom SE1 7LL - maria@puntohealth.com Public Anna Muñoz Farré https://orcid.org/0009-0004-0250-287X Public Scientific

CEO & Co-founder, Punto Health Ltd Health Foundry, 1 Royal Street

London United Kingdom SE1 7LL - anna@puntohealth.com Public Latha Velayudhan https://orcid.org/0000-0002-7712-930X Principal investigator

Clinical Reader in Ageing and Dementia Studies, Consultant Old Age Psychiatrist King’s College London and South London & Maudsley NHS Foundation Trust, 16 De Crespigny Park

London United Kingdom SE5 8AB - latha.velayudhan@kcl.ac.uk Public Punto Health Ltd Hospital/treatment centre Commercial National Institute for Health and Care Research http://dx.doi.org/10.13039/501100000272 UK Research and Innovation http://dx.doi.org/10.13039/100014013 Invention for Innovation Programme http://dx.doi.org/10.13039/501100009127 Science and Technology Facilities Council http://dx.doi.org/10.13039/501100000271