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

Equinox House, City Link

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

Prestwich Hospital Bury New Road Prestwich

Manchester England M25 3BL RXV@2.16.840.1.113883.2.1.3.2.4.18.48 Bethlem Royal Hospital

Monks Orchard Road

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

West Wing C E M E Centre Marsh Way

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

Bath NHS House Newbridge Hill

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

Migrated from study website field

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

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

Manchester United Kingdom M40 5BP +44 (0)161 271 0084 melissa.pyle@gmmh.nhs.uk Public Greater Manchester Mental Health NHS Foundation Trust Hospital/treatment centre https://ror.org/05sb89p83 Non-commercial National Institute for Health and Care Research http://dx.doi.org/10.13039/501100000272 31976295 true A feasibility study of eye-movement desensitization and reprocessing (EMDR) in people with an at-risk mental state (ARMS) for psychosis Psychotic illnesses are some of the most disabling illnesses, with more than 21 million people affected worldwide. These illnesses cause a huge burden on sufferers and their families. Approximately 22% of people with an at-risk mental state (ARMS) will make a transition to psychosis within 1 year. Current treatments to prevent the onset of psychosis are not very effective. More than 80% of the people at-risk of psychosis report traumatic events, especially during childhood. Studies suggested that memories of these events can lead to some people developing hallucinations (e.g. hearing voices) and delusions (e.g. paranoid beliefs), which are the most common symptoms of psychotic illnesses. Eye Movement Desensitisation and Reprocessing (EMDR) is a type of trauma-focused therapy which helps people deal with traumatic memories by changing how these are stored, and altering negative beliefs caused by the event (e.g. ‘It is my fault’). EMDR is an effective therapy for post-traumatic stress disorder, another illness caused by memories of traumatic events, but no studies have yet investigated whether EMDR could prevent the onset of psychosis in people at-high risk. To investigate this, a large randomised-controlled trial is needed. First, however, we need to investigate whether such a trial would be feasible and acceptable to patients. This study seeks to establish whether it would be feasible to conduct a large multi-centre RCT to evaluate the clinical and cost-effectiveness of EMDR to prevent the onset of psychosis in people with an at-risk mental state. Current plain English summary as of 01/08/2019: Background and study aims Psychotic illnesses are some of the most disabling illnesses, with more than 21 million people affected worldwide. These illnesses cause a huge burden on sufferers and their families. About 22% of people with an at-risk mental state (ARMS) will make a transition to psychosis within 1 year. Current treatments to prevent the onset of psychosis are not very effective. More than 80% of the people at-risk of psychosis report traumatic events, especially during childhood. Studies suggested that memories of these events can lead to some people developing hallucinations (e.g. hearing voices) and delusions (e.g. paranoid beliefs), which are the most common symptoms of psychotic illnesses. Eye Movement Desensitisation and Reprocessing ( EMDR) is a type of trauma-focused therapy which helps people deal with traumatic memories by changing how these are stored, and altering negative beliefs caused by the event (e.g. ‘It is my fault’). EMDR is an effective therapy for post-traumatic stress disorder, another illness caused by memories of traumatic events, but no studies have yet investigated whether EMDR could prevent the onset of psychosis in people at-high risk. To investigate this, a large randomized controlled trial is needed. First, however, the aim of this study is to investigate whether such a trial would be feasible and acceptable to patients. Who can participate? Patients aged 16 or over who are at risk of psychosis, have a history of trauma and at least one symptom of post-traumatic stress disorder. What does the study involve? Participants will be offered up to 12 EMDR sessions. Participants are followed up for 1 year, and data is collected on transition to psychosis and severity of symptoms. Patients and therapists are interviewed about their views of EMDR, study materials and participation experiences to help design a large study to find out whether EMDR is effective at preventing the development of psychotic illnesses. Additional qualitative work Recruitment to the study has been much lower than expected. It appears that one key reason for low recruitment is because the number of ARMS patients in the Early Intervention Services in AWP is much lower than expected based on data which had been given to us from the Trust prior to the study starting. Therefore the qualitative element of the study has been expanded to: 1) better understand how ARMS patients are managed in primary and secondary care settings, in order to identify possible reasons for why recruitment to the study has been much lower than expected and 2) consider how best to recruit ARMS patients to future research studies. In-depth interviews with GPs and clinicians from secondary care services will be conducted to explore how potential ARMS patients are identified in primary and secondary care, how they are managed, and the facilitators and barriers of referral to secondary care early intervention services. We would also like to interview UK researchers with experience of recruiting ARMS patients to their studies. Thus, the qualitative components of the study will entail: a. Interviews with GPs, clinicians from Primary Care Liaison Services and other secondary care services b. Interviews with patients who did not participate in the interventional part of the study but who have been identified as ARMS by the EI teams we are recruiting from c. Interviews with researchers who have been involved in recruiting ARMS patients to research studies in the UK What are the possible benefits and risks of participating? By taking part in this study, participants will help researchers better understand how to manage individuals who are at risk of developing psychosis. At the end of the study, participants will be sent a summary of the results. Patients will be asked to fill out questionnaires about traumatic experiences they had in the past. This may be upsetting for some of them. However, patients will be told prior to assessment that they do not have to answer a specific question if they do not feel comfortable doing so. Likewise, before the interview, patients will be told that they can stop the interview at any time and without having to give a reason. Their medical care will not be affected. The researchers administering the scales and conducting the interviews have previously worked in the area of mental health and dealt with sensitive issues. Where is the study run from? Avon and Wiltshire Mental Health Partnership NHS Trust (UK) When is the study starting and how long is it expected to run for? October 2017 to May 2021 (updated 29/05/2020, previously: April 2020) Who is funding the study? National Institute for Health Research (NIHR) (UK) Who is the main contact? Prof. Stanley Zammit Previous plain English summary: Background and study aims Psychotic illnesses are some of the most disabling illnesses, with more than 21 million people affected worldwide. These illnesses cause a huge burden on sufferers and their families. About 22% of people with an at-risk mental state (ARMS) will make a transition to psychosis within 1 year. Current treatments to prevent the onset of psychosis are not very effective. More than 80% of the people at-risk of psychosis report traumatic events, especially during childhood. Studies suggested that memories of these events can lead to some people developing hallucinations (e.g. hearing voices) and delusions (e.g. paranoid beliefs), which are the most common symptoms of psychotic illnesses. Eye Movement Desensitisation and Reprocessing (EMDR) is a type of trauma-focused therapy which helps people deal with traumatic memories by changing how these are stored, and altering negative beliefs caused by the event (e.g. ‘It is my fault’). EMDR is an effective therapy for post-traumatic stress disorder, another illness caused by memories of traumatic events, but no studies have yet investigated whether EMDR could prevent the onset of psychosis in people at-high risk. To investigate this, a large study is needed. First, however, the aim of this study is to investigate whether such a study would be feasible and acceptable to patients. Who can participate? Patients aged 16 or over who are at risk of psychosis and have a history of trauma What does the study involve? Participants are randomly allocated to either 12 EMDR sessions or treatment as usual (TAU). Participants are followed up for 1 year, and data is collected on transition to psychosis and severity of symptoms. Patients and therapists are interviewed about their views of EMDR, study materials and participation experiences to help design a large study to find out whether EMDR is effective at preventing the development of psychotic illnesses. What are the possible benefits and risks of participating? By taking part in this study, participants will help researchers better understand how to manage individuals who are at risk of developing psychosis. At the end of the study, participants will be sent a summary of the results. Patients will be asked to fill out questionnaires about traumatic experiences they had in the past. This may be upsetting for some of them. However, patients will be told prior to assessment that they do not have to answer a specific question if they do not feel comfortable doing so. Likewise, before the interview, patients will be told that they can stop the interview at any time and without having to give a reason. Their medical care will not be affected. The researchers administering the scales and conducting the interviews have previously worked in the area of mental health and dealt with sensitive issues. Where is the study run from? Avon and Wiltshire Mental Health Partnership NHS Trust (UK) When is the study starting and how long is it expected to run for? October 2017 to April 2020 Who is funding the study? National Institute for Health Research (NIHR) (UK) Who is the main contact? Prof. Stanley Zammit Transition to psychosis assessed at 12 months post-randomization from clinical records (measured as an ICD-10 diagnosis of psychosis) or, if patients have dropped out of the Early Intervention Services, researchers will invite participants for an appointment where, via the CAARMS, it will be established whether they transitioned to psychosis. Current secondary outcome measures as of 01/08/2019: 1. Severity of psychotic symptoms, measured using CAARMS, PSYRAT, the negative scale of the PANSS, and CAPE-42 2. Severity of PTSD symptoms, measured using PCL-5 3. Severity of depression and anxiety, measured using PHQ-9 and GAD-7 4. Impaired functioning, measured using Work and Social Adjustment Scale (WSAS) 5. Health status, measured using EQ-5D-L 6. Drug use, measured using DAST 10 7. Medication use, measured with self-report questionnaires 8. Resource data use, measured with self-report questionnaires All secondary outcomes apart from resource data use will be assessed at baseline, 4, 8 and 12 months after the baseline assessment. Resource use will be assessed only at 4, 8 and 12 months after the baseline assessment. Previous secondary outcome measures: 1. Severity of psychotic symptoms, measured using PANSS, PSYRAT and CAPE-42 2. Severity of PTSD symptoms, measured using PCL-5 3. Severity of depression and anxiety, measured using PHQ-9 and GAD-7 4. Impaired functioning, measured using Work and Social Adjustment Scale (WSAS) 5. Health status, measured using EQ-5D-L 6. Drug use, measured using DAST 10 7. Medication use, measured with self-report questionnaires 8. Resource data use, measured with self-report questionnaires All secondary outcomes apart from resource data use will be assessed at baseline, 4, 8 and 12 months post-randomization. Resource use will be assessed only at 4, 8 and 12 months post randomization. Old ethics approval format South West - Exeter Research Ethics Committee, 19/03/2018, ref: 18/SW/0037 10.1186/ISRCTN31976295 37404 37404 Current study design as of 11/07/2019: Single arm interventional study. Previous study design: Randomised; Interventional; Design type: Treatment, Prevention, Psychological & Behavioural Interventional Non randomised study Prevention 2021-05-31T00:00:00.000Z United Kingdom England Avon and Wiltshire Mental Health Partnership NHS Trust

United Kingdom BS15 9TR Patient 1. Those aged 16 years or over who are at risk of psychosis (as defined in the Comprehensive Assessment of At-Risk Mental States (CAARMS) (A. R. Yung et al., 2005) 2. Presence of at least one positive symptom (perceptual abnormality, unusual thought, or non-bizarre ideas) scored ≥3 on CAARMS 3. History of traumatic experience as defined in ICD-10 F43.1, occurring prior to onset of first positive symptom 4. Presence of 1 or more symptoms of re-living, avoidance, hyper-arousal, or cognitive distortions in relation to the traumatic experience (assessed using the PTSD Checklist for DSM-V (PCL5) during the last month (Bovin et al., 2016)) Adult All 20 14 1. People with past history of treated or untreated psychotic illness or learning disability 2. Current use of antipsychotics 3. Currently receiving psychological therapy 4. Completed a trauma-focused psychological therapy in the last 2 years 5. Insufficient fluency in English 6. Lacking mental capacity to provide valid informed consent 2018-05-01T00:00:00.000Z 2020-05-31T00:00:00.000Z Psychosis Mental and Behavioural Disorders Unspecified organic or symptomatic mental disorder Current interventions as of 01/08/2019: We originally planned to randomise all consented participants to one of the two groups: 1) EMDR or 2) TAU. Randomization took place by means of a computerized service administered by the Bristol Randomised Trials Collaboration (BRTC). This ensured that allocations were concealed from the recruiting researcher. Randomization was minimized by psychotic symptom severity and patients were categorized based on the positive symptoms of CAARMS (i.e, sum of Unusual Thoughts, Non-Bizarre Ideas, Perceptual Abnormalities and Disorganised Speech Global Ratings scales), with cut-off at 11 on this scale. Participants were notified of their group allocation within 48 hours of the baseline assessment. Given the change in study design from a randomised controlled trial to a single arm trial, all eligible consenting participants will now be offered EMDR. Patients will receive up to 12 sessions of manualized, weekly, face-to-face EMDR therapy. Each session will last approximately 90 minutes. EMDR therapy sessions will be held by trained EMDR therapists at the EI services, GP Surgeries, or other NHS/private clinical premises. Participants will be followed up for 1 year, and data on transition to psychosis and severity of symptoms will be collected. Patients and therapists will be interviewed about their views of EMDR, study materials and participation experiences by telephone or face-to-face at the EI services. Follow-up assessments will take place at 4, 8 and 12 months after the baseline assessment. This will take place either at the EI Services, University of Bristol premises or at participants' home. Previous interventions: Randomization will take place by means of a remote automated telephone service administered by the Bristol Randomised Trials Collaboration (BRTC). Randomization will be minimized by psychotic symptom severity and patients will be categorized based on the positive symptoms of CAARMS (i.e, sum of Unusual Thoughts, Non-Bizarre Ideas, and Perceptual Abnormalities Global Ratings scales), with cut-off at 11 on this scale. Participants will be randomly allocated to eye-movement desensitization and reprocessing (EMDR) sessions or treatment as usual (TAU). Patients allocated to EMDR will receive up to 12 sessions of manualized, weekly, face-to-face EMDR therapy. Each session will last approximately 90 minutes. EMDR therapy sessions will be held by trained EMDR therapists at the EI services. Participants will be followed up for 1 year, and data on transition to psychosis and severity of symptoms will be collected. Patients and therapists will be interviewed about their views of EMDR, study materials and participation experiences by telephone or face-to-face at the EI services. Follow-up assessment at 4, 8 and 12 months post-randomization. This will take place either at the EI Services or at participants' home. Other The datasets generated during and/or analysed during the current study are/will be available upon request from Prof. Stanley Zammit. Data will be available 1 year after the end of the study. Available on request 2024 Results article in https://doi.org/10.1192/bjo.2024.57 (added 25/06/2024) 2020 Protocol article in https://pubmed.ncbi.nlm.nih.gov/33004398/ protocol (added 07/10/2020) Results

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Unreferenced after processing basic results

Unreferenced after processing basic results

8763f251-7422-4bd1-b143-b27d1a61322f 2bebca74-4b97-4e2b-8207-81ea4bc31841 a89409ce-194d-4618-935f-6f1946dfa2f2 Yes Uploaded 03/05/2018 ISRCTN31976295_PROTOCOL_11Jan2018_V1.pdf 21076ec1-2323-403e-88aa-4eced2a907c4 true application/pdf 555438 b5146efa3b3fa8da81952a02087d8401 Uploaded 03/05/2018 ISRCTN31976295_PIS_06Mar2018_V2.pdf 3e9bf000-fa44-4bf9-a944-61311571e897 true application/pdf 302062 e0eadea115b1eb2a14853af61c71dfab uploaded 11/07/2019 ISRCTN31976295_PROTOCOL_19Apr2019_V3.pdf 99b18ad5-ac5e-4fb0-9080-d87ed94454da true application/pdf 344888 7e020e8082a8a4c2b4a5dfd9b5dc38d1 uploaded 14/01/2020 ISRCTN31976295_Protocol_v4_02Aug19.pdf d862de6e-759b-460a-8fc8-2aa98680086b true application/pdf 527867 7629724a3d4c162f5358a13568ae087a Stanley Zammit https://orcid.org/0000-0002-2647-9211 Scientific

Oakfield House Oakfield Grove

Bristol United Kingdom BS8 2BN Protected University of Bristol Hospital/treatment centre https://ror.org/0524sp257 Non-commercial NIHR Bristol Biomedical Research Centre; Grant Codes: BRC-1215-20011 87426020 true Scaling early childhood development at Anganwadi Centers in India 400 (50%) of the total children enrolled in the intervention arm show at least 0.3SD changes in cognitive/behavioral measures compared to the control. Background and study aims Anganwadi centers are early childhood development centers under the Integrated Child Development Programme of India (ICDS). Over time, their focus on early childhood education and development activities has reduced and their current activities mostly revolve around nutritional supplementation and assisting the health workers in Maternal and Child Health services. This study aims to enhance the behavioural and cognitive development of children under 6 years of age by actively engaging with Anganwadi workers, parents, caregivers and the community, improving the curriculum, and assisting Anganwadi workers, caregivers and parents through continuous guidance. We also intended to increase the parents’ and caregivers’ knowledge and skills for health and early childhood development. Who can participate? Children under 6 years and their families What does the study involve? Participating anganwadi centers are randomly allocated to either the intervention or the control group. The control group receive the standard Anganwadi Worker Program. The intervention group receive the intervention described below. A family centred early childhood development and positive parenting curriculum is developed and delivered through the Anganwadi centers, targeting children aged 3 to 6 years. The parenting program is delivered through group meetings and home visits and primarily targets the parents of children under three years of age. The project actively engages with private preschool, higher education institutions and the community for assessments and continues monitoring and coaching Anganwadi workers and project staff for continued quality improvement. The study participants are assessed for changes in cognitive development at the end of the study. What are the possible benefits and risks of participating? Participating children may benefit from improved cognitive and behavioural development. Parents and caregivers may benefit from improved knowledge and skills for positive parenting. The Anganwadi Workers and teachers may benefit from improved knowledge and skills to deliver the enhanced curriculum. We anticipate no risks for participants. Where is the study run from? Datta Meghe Institute of Medical Sciences (India) When is the study starting and how long is it expected to run for? December 2015 to September 2016 Who is funding the study? Grand Challenges Canada Who is the main contact? 1. Dr Abhay Gaidhane 2. Dr Zahir Quazi 1. 400 (50%) of the total children enrolled in the intervention arm show at least 0.3SD changes in cognitive/behavioral measures compared to the control. 2. Increase in AWC attendance from 30% to 50% 3. Increase in the number of Baby Friendly Couples Primary and secondary outcomes will be measured at Endline i.e. in September 2016. Battery of tools to be used for assessment are Developmental Milestones Checklist - III (DMC-III), Profile of Socio-Emotional Development (PSED), Home Scale Coding, Early Childhood Home Inventory, Memory Game and Windows Task, Maternal Depression Agency and Depression. 1. Number of Anganwadi workers enrolled and benefited in the intervention arm 2. Number of families benefited through positive parenting sessions Primary and secondary outcomes will be measured at Endline i.e. in September 2016 Old ethics approval format Datta Meghe Institute of Medical Sciences Ethics Committee, 30/03/2015, Ref. No. DMIMS (DU)/IEC/2014-15/1203 10.1186/ISRCTN87426020 Interventional multicenter cluster randomised trial Interventional Cluster randomised trial Other 2016-09-30T00:00:00.000Z India Datta Meghe Institute of Medical Sciences, Sawangi (M), Wardha

Sawangi Meghe Wardha

Wardha India 442001 true 1. Children aged 0-6 years 2. Family members of children aged 0-6 years Mixed All 1600 0 Children older than 6 years of age 2015-12-01T00:00:00.000Z 2016-09-30T00:00:00.000Z Six domains of child development Other Anganwadi workers (AWW), local community-based workers under the Integrated Child Development Scheme (ICDS), established in 1975, provide supplementary nutrition, preschool education, nutrition and health education and referral services. Despite their significant role in child development, AWW are often overburdened due to administrative and documentation related work. Our innovation is the integration and enhancement of the existing government Anganwadi Program (AWP) and Anganwadi Worker (AWW) with local resources in the private and education sectors to create a higher-impact program for early childhood development (ECD) of indigenous tribal groups. Novel elements are: 1. Creation of a tailored curriculum for a family-centered approach and certification of baby-friendly couples (BFC) to increase caregiver capacities for health and ECD 2. Deploying a tablet-PC smart register application as a tool for the AWW to adequately track child growth and ECD and progress through the curriculum, highlight gaps in care for targeted action, and reduce administrative and reporting burdens 3. Creating training and apprentice partnerships between the public AWP/AWW and private high quality preschools as a mechanism for AWW performance incentives and training including recognition as an upgraded Anganwadi Center (Anganwadi Plus) 4. Establish partnerships with local community colleges and medical schools for continuous data driven quality improvement and training. Research Assistants in the project will support the impact evaluation, coordinate between community colleges/medical colleges and private school teachers with the AWW, and provide technical support for the application. The proof of concept for this project is that the intervention can be effectively delivered through a public-private partnership (shown by attendance in AWC increasing from 30% to at least 50%). We are using a cluster randomized controlled trial to evaluate the impact of the intervention. This will include 50 clusters comprised of an Anganwadi Center (AWC). The selected AWC will be randomly allocated to either intervention or control. We anticipate equal distribution of unaccounted variables across both groups. The baseline comparability will be assessed as a proxy for general comparability. The intervention group is receiving the intervention as described steps 1-7 below, and the control will receive the standard Anganwadi Worker Program. Information on the fidelity of implementation related to training and deployment will be collected. Attendance of children at the AWC, engagement with parents and use of the smart register application to manage clients and provide customized feedback to parents will also be tracked. Intervention: Step 1: to develop an enhanced AWP curriculum through integration and adaptation of early childhood education tools. The curriculum will be family-focused with a substantial parental role in child interaction skills and a supportive home environment. Step 2: training and certification of staff to deliver the new curriculum and procedures, first for private preschool teachers who will also be trained as trainers, and then for AWW. Step 3: concurrent with Step 2, we will develop the smart register application and tablet PCs for the AWW to manage their clients. Step 4: the AWW workers in tribal areas “go live” with the enhanced curriculum, BFC sessions and tablets. Step 5: private preschool teachers will begin their role as mentors by visiting AWC/AWW for coaching and quality assessments. Step 6: engaging local academics and scholars at a local college/medical school and train them to review the AWW register data, and analyse and identify service gaps. Step 7: monthly community meetings held with the AWW, supervisors, mentors from the private preschools, academics and community members. At these meetings the stakeholders discuss the successes and failures at the AWC/AWW and formulate a plan to improve services based on the data. Other The datasets generated during and/or analysed during the current study are/will be available upon request Available on request 2025 Other publications in https://pubmed.ncbi.nlm.nih.gov/40837957/ Embedded mixed-methods study on community engagement (added 10/06/2026)

Embedded mixed-methods study on community engagement

00add602-fd32-433b-9d60-3e4d0b201967 9b77ce45-f1b1-4f65-87a2-a13bfa9eb899 c627f73f-40c0-40da-bbf2-18cbec417650 e67bee00-9125-4332-8842-be3ef38da4a4 Yes Abhay Gaidhane https://orcid.org/0000-0002-4814-2695 Scientific

Project Cell Jawaharlal Nehru Medical College Datta Meghe Institute of Medical Sciences Sawangi Meghe

Wardha India 442001 Protected Zahir Quazi https://orcid.org/0000-0002-1435-899X Public

Project Cell Jawaharlal Nehru Medical College Datta Meghe Institute of Medical Sciences Sawangi Meghe

Wardha India 442001 Protected Grand Challenges Canada Government https://ror.org/02snbhr24 Non-commercial Grand Challenges Canada http://dx.doi.org/10.13039/501100004828 19083628 true A single-blind randomised controlled trial to determine the effectiveness of group Cognitive Behaviour Therapy (CBT) in the prevention of depression in high risk adolescents Group based CBT delivered in schools is effective and cost effective in preventing depression in adolescents at high risk of depression. More details can be found at: http://www.nets.nihr.ac.uk/projects/hta/063704 Protocol can be found at: http://www.nets.nihr.ac.uk/__data/assets/pdf_file/0006/51378/PRO-06-37-04.pdf Background and study aims We aim of this study is to test whether a school-based depression prevention programme developed in Australia, the Resourceful Adolescent Programme (RAP), is effective at reducing depressive symptoms in high-risk children in the UK. Who can participate? Children aged 13-16 from 9-12 mixed comprehensive schools in Bath, Bristol, Nottingham and Swindon What does the study involve? Participants complete a questionnaire. Their scores are used to categorise them as either low or high risk of depression or probably depressed. We want to find out what happens to the high risk group (about 20% of each class). Whole classes of children are randomly assigned to receive either the RAP, a placebo (dummy) intervention, or treatment as usual (Personal Health and Social Education - PHSE). For RAP and the placebo intervention each student has a workbook and sessions are led by trained and supervised mental health professionals. We assess children's mood, negative thoughts and self-image before we start and again at 6 and 12 months. This allows us to see whether RAP is effective and if these gains last. We also want to find out whether RAP is good value and so we work out how much it costs and what it saves. What are the possible benefits and risks of participating? Not provided at time of registration Where is the study run from? Royal United Hospital (UK) When is the study starting and how long is it expected to run for? September 2008 to December 2011 Who is funding the study? NIHR Health Technology Assessment Programme - HTA (UK) Who is the main contact? Prof. Paul Stallard paul.stallard@awp.nhs.uk Changes in depression symptoms as assessed by the short form Mood and Feelings Questionnaire at 12 months follow-up. 1. Changes in self-image and negative thoughts. These will be assessed at 12 months by the following questionnaires: 1.1. Self Image Profiles (SIP-A). An easily competed 25-item scale for adolescents assesses how they perceive themselves and how they would like to be. Twelve items assess positive attributes (e.g. confident, fun to be with), twelve assess negative attributes (e.g. annoying, moody) and one is neutral (i.e. feel different from others). 1.2. Children's Automatic Thoughts Scale (CATS). This self-completed scale assesses a range of negative self statements in children and young people aged 7-16. For each item the child is asked to rate whether they have had a similar thought over the past week. Each item is rated as "not at all" (scores 0), "sometimes" (scores 1), "fairly often" (scores 2), "often" (scores 3) or "all the time" (scores 4). The 10-item personal failure sub-scale will be used. 2. Cost effectiveness at 12 months Old ethics approval format University of Bath Ethical Committee: School for Health: School Research Ethics Approval Panel (SREAP), 18/12/2007 10.1186/ISRCTN19083628 HTA 06/37/04 HTA 06/37/04 Cluster randomised controlled trial. Interventional Cluster randomised trial Prevention 2011-12-31T00:00:00.000Z United Kingdom England Royal United Hospital

Bath United Kingdom BA1 3NG Patient All children aged 13-16 attending participating schools (n = 8-12) Child 13 Years 16 Years All 5000 5030 No exclusion criteria 2008-09-01T00:00:00.000Z 2011-12-31T00:00:00.000Z Depression Mental and Behavioural Disorders Depression Interventions will be provided during the usual Personal, Social and Health Education (PSHE) sessions (1 hour per session, total of 11 sessions over one school term). Arm A: Group CBT. CBT recognises the importance of negative thoughts and low self-worth/image in the onset and maintenance of depression. These are therefore actively targeted during CBT with core treatment components including psycho education, identifying and challenging negative/dysfunctional thoughts, identifying personal strengths (thereby enhancing self-esteem/image), managing social problems, and learning to problem solve. Arm B: Attention placebo. The attention placebo intervention will involve similar time and contact with an external group leader but will not include the active components of the CBT intervention. The content will be based upon the PSHE provided in schools but will be provided by leaders from outside of the school. This will therefore control for the non-specific effects of interventions that are considered important in studies of depression. Arm C: Usual PSHE Other Not Specified 2013 Results article in http://www.ncbi.nlm.nih.gov/pubmed/24172024 results 2014 Results article in http://www.ncbi.nlm.nih.gov/pubmed/24813670 cost-effectiveness results 2012 Results article in https://www.ncbi.nlm.nih.gov/pubmed/23043090 results (added 08/05/2019) 2010 Protocol article in http://www.ncbi.nlm.nih.gov/pubmed/21114808 protocol Results

results

cost-effectiveness results

results

protocol

1b3d21c2-e999-4bf9-8fe7-3af2c65a6aa9 20d4f1c1-90bf-4dd0-ab05-2f76139a2513 83394428-b840-4966-a531-a075f083061b No Paul Stallard Scientific

Department of Child and Family Psychiatry Royal United Hospital Combe Park

Bath United Kingdom BA1 3NG +44 (0)1225 383860 paul.stallard@awp.nhs.uk Public University of Bath (UK) University/education https://ror.org/002h8g185 Non-commercial Health Technology Assessment Programme http://dx.doi.org/10.13039/501100000664 38174888 true Serotonin sensitivity in insomnia: a placebo-controlled crossover study of sleep after 5HT2 blockade in primary insomnia Does Trazodone improve sleep in primary insomnia? Not provided at time of registration Sleep efficiency: % Total Sleep Time / Staging Time. 1. Daily symptom report (DSR) 2. Total sleep time (TST) 3. Number of awakenings 4. Wake Time After Sleep Onset (WASO) 5. Time spent in stages 1 to 4 and rapid eye movement (REM), %TST spent in each stage 6. REM onset latency 7. Sleep onset Latency (SOL), slow wave activity 8. Leeds Sleep Evaluation Questionnaire. Old ethics approval format Bath Research Ethics Committee, 21/04/2006, REC ref: 06/Q2001/32. 10.1186/ISRCTN38174888 N0038183440 N0038183440 Randomised double-blind placebo-controlled crossover study Interventional Randomised cross over trial Treatment 2009-01-31T00:00:00.000Z United Kingdom England University of Bristol

Bristol United Kingdom BS1 3NY Patient 1. Adults referred to Psychopharmacology Unit Clinic 7, Bristol Royal Infirmary with psycho-physiological insomnia 2. Complaint of poor sleep with daytime consequences Adult All 12 12 1. Taking psychotropic medication 2. Total sleep time (subjective) < 6.5 hours 3. Current psychiatric disorder 2006-04-28T00:00:00.000Z 2009-01-31T00:00:00.000Z Nervous System Diseases: Primary insomnia Nervous System Diseases Primary insomnia Trazodone vs placebo. Overnight sleep patterns recorded and compared, after either placebo or trazodone 100mg. Each patient has screening visit and 2 overnight sleep recordings at home a week apart, plus an end-of study visit. Drug Not Applicable Trazodone Not provided at time of registration 2009 Abstract results in https://doi.org/10.1016/S0924-977X(09)70593-0 conference abstract (added 21/06/2019) 2011 Other publications in https://www.ncbi.nlm.nih.gov/pubmed/21490119 review article (added 21/06/2019) Results

conference abstract

review article

2e7d074a-7c64-4db0-a26a-b4d15293f961 9a50be9d-caee-4366-84a3-207d41853030 b6fb3db5-d073-4bee-a9ab-2d42d77bb40e f1383f93-2cce-4ced-af8c-1b309f8e2046 edf69e8a-9218-4b08-bfcf-b468cae8432d No Sue Wilson Scientific

University of Bristol Dorothy Hodgkin Building Whitson Street

Bristol United Kingdom BS1 3NY +44 0117 331 3172 sue.wilson@bris.ac.uk Public Record Provided by the NHSTCT Register - 2007 Update - Department of Health Government Non-commercial Avon and Wiltshire Mental Health Partnership NHS Trust (UK) AWP Partnership Mental Health NHS Trust R&D Project grant NHS R&D Support Funding