91960330 true A randomised controlled trial to examine the feasibility of a weight management programme prior to surgery with embedded qualitative study PreWel The primary objective is to examine the feasibility and acceptability of referring participants and the participation in a weight management programme to improve post-operative outcomes. The trial also aims to assess: 1. Weight change from start of programme to pre-surgery and from the start of programme to post-surgery 2. Unexpected, serious adverse events during the weight management programme and post-surgery (up to 90 days) To see if we can collect data for a future trial: 1. Complications from surgery 2. Health care resource use 3. Health-related quality of life To examine the processes involved for the feasibility trial and allow refinement for a future trial we will: 1. Examine engagement with weight management 2. Examine heterogeneity between surgical operations 3. Examine contamination with the comparator group 4. Describe who takes part in the trial to assess equality, diversity and inclusion 5. Examine methods to collect postoperative data Background and study aims About one-third of people on NHS surgical waiting lists live with obesity. Living with obesity prior to surgery may increase the risk of surgical complications, such as wound infections, heart problems, and longer hospital stays. Although effective weight management programmes exist, they are not routinely offered to patients while they wait for surgery. The PRE Weight Loss (PRE-WEL) study aims to find out whether it is practical and acceptable to offer free weight management programmes to patients preparing for surgery. The study will also measure weight changes, hospital stay length, surgical complications, quality of life, and healthcare resource use to help design a future larger-scale trial. Who can participate? Patients aged 18 years or older with Body Mass Index (BMI) 30 kg/m² or higher, who are referred for hip or knee joint replacement, laparoscopic cholecystectomy (gallbladder removal), hysterectomy, or coronary artery bypass graft and/or valve surgery (between 1 and 6 months before their scheduled operation date) What does the study involve? Participants will be randomly placed into one of two groups: 1. The weight management group are offered a choice of free weight management programmes) to access for 1 to 6 months before surgery. 2. The booklet group are given an NHS weight management information booklet. Participants will complete short questionnaires and send a photograph of their weight reading from home scales at the start, shortly before surgery, and 90 days after surgery. Surgical details and post-surgery recovery information will also be collected from hospital and GP records. Participants can optionally choose to take part in interviews or keep voice/paper diaries sharing their experiences. What are the possible benefits and risks of participating? Participants receive free access to a structured weight loss programme or booklet, which may help them lose weight before surgery. All participants contribute to research aimed at improving pre-operative NHS care. Participants receive a £20 voucher each time for completing follow-up assessments or qualitative sub-studies. The overall risk is low and no higher than standard NHS care. Weight management programmes are non-invasive. Where is the study run from? The study is managed by Loughborough University (Centre for Lifestyle Medicine and Behaviour) in partnership with the Leicester Clinical Trials Unit (LCTU) (UK) When is the study starting and how long is it expected to run for? November 2026 to August 2029 Who is funding the study? National Institute for Health and Care Research (NIHR) (UK) Who is the main contact? Dr Claire D. Madigan, prewel@mailbox.lboro.ac.uk The feasibility and acceptability of referral and participation in a weight management programme before surgery, the number of participants randomised after a 12-month recruitment period; engagement with the intervention; retention rate: the number of participants follow-up (pre-surgery and 90-days post-surgery) as a proportion of participants randomised; embedded think aloud study and qualitative interviews with participants will examine the acceptability of referral and participation in weight management programmes 1. Change in weight measured in kg from baseline to pre-surgery and baseline to 90 days post-surgery 2. Number of serious adverse events occurring prior to surgery as a proportion of participants randomised 3. Number of serious adverse events occurring during surgery and up to 90-days post-surgery as a proportion of participants randomised 4. The proportion of participants with no specified complications related to surgery, hospitalization or mortality from date of surgery up to 90 days post-surgery 5. The proportion of participants that are readmitted to hospital, have a re-operation or mortality within 90 days post-surgery 6. Length of stay (LOS), defined as the time in days between admission for surgery and discharge from surgery 7. Surgery duration, measured in minutes as recorded in hospital notes 8. The number of participants with complete data as a proportion of participants randomised when quality of life is measured using EQ-5D-5L at baseline, pre-surgery and 90-days post-surgery 9. Engagement data collected from the weight management programmes 10. The length of access to the weight management programme, defined as the time between first attendance and their surgery 11. Heterogeneity between surgical operations measured using the means (SD) and proportions by surgical operation of the weight change data and the postoperative complications 12. Whether weight management interventions are delivered as planned and patient’s experiences of the intervention, measured using qualitative interviews and think aloud sub-study during the weight management programme 13. Comparator group contamination measured using: 13.1. Proportion of participants randomised to the comparator arm whose weight pre-operatively remains within 2 kg of baseline weight 13.2. Proportion of the comparator that actively managed their weight pre-operatively, defined as answering yes to the question about actively managing their weight and answered yes to options other than “I have been following the plan” 14. Number and proportion (of randomised) participants by age, sex, ethnicity, index of multiple deprivation, comorbidities, malnutrition status (as measured using PS-SGA short form) and long-term health condition 15. The number of participants with data collected from hospital records, GP data and patient-reported data as a proportion of participants randomised, reported separately for each method Ethics approval required London - Bromley Research Ethics Committee

2 Redman Place, Stratford

London United Kingdom E20 1JQ 26/LO/0622 10.1186/ISRCTN91960330 371974 CPMS: 74081, NIHR: 303187 371974 74081 303187 Interventional Randomized controlled trial Blinded (masking used) Active Parallel Treatment Not applicable Treatment 2029-08-01T00:00:00.000Z United Kingdom England Loughborough University

Epinal Way

Loughborough England LE11 3TU 10004113@2.16.840.1.113883.2.1.3.8.2.9.1 University of Leicester

Department of Cardiovascular Sciences University of Leicester Glenfield Hospital

Leicester England LE3 9QP University Hospitals Bristol and Weston NHS Foundation Trust

Marlborough Street

Bristol England BS1 3NU North Bristol NHS Trust

Southmead Hospital Southmead Road Westbury-On-Trym

Bristol England BS10 5NB University Hospitals of Leicester NHS Trust

Leicester Royal Infirmary Infirmary Square

Leicester England LE1 5WW RWE@2.16.840.1.113883.2.1.3.2.4.18.48 University Hospitals Birmingham NHS Foundation Trust

Queen Elizabeth Hospital Mindelsohn Way Edgbaston

Birmingham England B15 2GW RRK@2.16.840.1.113883.2.1.3.2.4.18.48 University Hospitals of Derby and Burton NHS Foundation Trust

Royal Derby Hospital Uttoxeter Road

Derby England DE22 3NE RTG@2.16.840.1.113883.2.1.3.2.4.18.48 South Tees Hospitals NHS Foundation Trust

James Cook University Hospital Marton Road

Middlesbrough England TS4 3BW RTR@2.16.840.1.113883.2.1.3.2.4.18.48 false 1. Aged >=18 years 2. Referred for hip/knee replacement, laparoscopic cholecystectomy, hysterectomy or coronary artery bypass graft and/ or valve surgery 3. Body mass index (BMI) >=30 kg/m2 Mixed 18 Years 100 Years All 120 0 1. Greater than 6 months to operation date or less than one month before operation date 2. Urgent/emergency or surgery listed outside of the inclusion criteria 3. Currently/recently enrolled in a weight management programme or lost >3 kg of weight in the last 3 months 4. Women known to be pregnant of breastfeeding 5. History of eating disorders within the last 10 years 6. Any other significant disease or disorder which, in the opinion of the investigator or healthcare team, may put the participant at risk because of participation in the trial (e.g., serious mental health concerns) 2026-11-01T00:00:00.000Z 2028-01-01T00:00:00.000Z Hip/knee joint replacement, laparoscopic cholecystectomy, hysterectomy, or coronary artery bypass graft/valve surgery Surgery Participants will be randomised stratified by surgical speciality (hip/knee joint replacement, laparoscopic cholecystectomy, hysterectomy or coronary artery bypass graft and/ or valve surgery) using random block sizes. Participants will be randomly assigned (1:1) to either: 1. Intervention arm: free referral to a weight management programme of their choice for up to 6 months before surgery. 2. Control arm: delivery of a NHS weight management booklet. Data will be collected at baseline, 1 week pre-surgery, and 90 days post-surgery via electronic questionnaires and participant-submitted weight photographs. Optional embedded qualitative sub-studies (interviews and WhatsApp "think aloud" voice notes) will gather real-time data on participant experiences. Progression to a full-scale trial will be guided by definitive traffic-light criteria tracking recruitment and retention rates. Behavioural Data sharing statement to be made available at a later date 9da547d7-3ed5-4621-b23c-a9cd4a4966d2 2c3f3ad7-da40-4f6c-b1c0-356fbb899599 34d7a2d8-c1c0-4c63-b4bd-ee68a8d86ae9 fac32cb1-3489-4ba9-bda8-c02c215fe374 No Claire Madigan https://orcid.org/0000-0002-6782-0017 Principal investigator

School of Sport Exercise and Health Sciences, Loughborough University, Epinal Way

Loughborough United Kingdom LE11 3TU +44 (0)1509223008 c.madigan@lboro.ac.uk Public Charlotte Doleman Public Scientific

School of Sport Exercise and Health Sciences, Loughborough University, Epinal Way

Loughborough United Kingdom LE11 3TU +44 (0)1509226501 C.L.Doleman1@lboro.ac.uk Public Loughborough University Hospital/treatment centre https://ror.org/04vg4w365 Non-commercial National Institute for Health and Care Research http://dx.doi.org/10.13039/501100000272 16804705 true Indoor Versus OutdooR group psychological therapy for older adults in NHS inpatient settings; a feasibility study of a pragmatic, cluster randomized controlled trial (RCT) IVOR This is a small-scale pilot study designed to assess whether a larger trial would be feasible. The study compares indoor and outdoor group psychological therapy for older adults receiving NHS inpatient care. It will assess how practical and acceptable it is to deliver the two approaches and whether the study procedures are manageable. The findings will help determine whether and how a larger trial could be conducted in the future. Background and study aims People who spend time outdoors may experience benefits to their mental health and wellbeing, such as reduced stress and improved mood. However, psychological therapy in NHS hospitals is usually delivered indoors. There is some evidence that providing psychological therapy outdoors may help people feel better and become more engaged with therapy, but there is not yet enough research to know whether this is practical and beneficial for older adults receiving care in NHS hospitals. This study will compare group psychological therapy delivered indoors with the same type of therapy delivered outdoors for older adults staying in NHS hospital wards. The study will help us understand whether outdoor psychological therapy is practical and acceptable for patients and staff. It will also help us decide whether a larger study should be carried out in the future. Who can participate? People who are currently receiving care on dementia and frailty inpatient wards at Birmingham and Solihull Mental Health NHS Foundation Trust may be able to take part. Participants will need to have been invited to attend group psychological therapy and be able to give informed consent to take part in the research. Staff involved in delivering or supporting the therapy may also be invited to provide their views about delivering psychological therapy outdoors. What does the study involve? Participants who agree to take part will attend group psychological therapy as part of their usual care. The therapy will be delivered either indoors or outdoors. The ward will be assigned to either the indoor or outdoor therapy group, meaning that participants on the same ward will receive the same type of therapy. Participants will not individually choose whether their therapy is delivered indoors or outdoors. Participants will be asked to complete questionnaires about their wellbeing and their experience of the therapy. These questionnaires will be completed before the therapy, after the therapy, and again approximately 3 months later. The study will also collect information about how many people agree to take part, whether participants attend the therapy sessions, and whether the therapy can be delivered as planned. Staff will be asked about their experience of delivering therapy outdoors. What are the possible benefits and risks of participating? Benefits: This study will help us to consider the feasibility of delivering outdoor psychological therapy. Whilst there may be no immediate benefits to participants, the aim is to improve care for future patients on the ward. Risks: Some of the disadvantages of taking part are that participants may find it time consuming to complete the questionnaires and that they will not be able to choose where the group psychological therapy is conducted (indoors or outdoors) as it is randomly allocated. For participants who receive outdoor group psychological therapy, they may be exposed to adverse weather conditions, they may find it more difficult to walk to the venue, and there may be less privacy. Taking part is voluntary, and participants can choose not to take part or withdraw from the research without this affecting their usual care. Where is the study run from? The study is sponsored by the University of Birmingham and is delivered at Birmingham and Solihull Mental Health NHS Foundation Trust. It will take place on dementia and frailty inpatient wards within the Trust, including the Juniper Centre and Reservoir Court. When is the study starting and how long is it expected to run for? The study started recruitment in May 2026 and the study will end in January 2027. Who is funding the study? Investigator initiated and funded. Who is the main contact? Dr Stephanie Howarth Principal Investigator s.l.howarth@bham.ac.uk Recruitment rates Number and proportion of eligible participants recruited to the study, measured against the target recruitment of 16–24 participants. Recruitment rate will be calculated as the number of participants consenting to take part divided by the number of eligible participants approached/invited, expressed as a percentage. The number recruited per week will also be recorded from the start of participant recruitment until the end of the recruitment period (approximately 16 weeks). Acceptability of intervention Acceptability of Intervention Measure post-intervention Ethics approval required Seasonal REC

2 Redman Place Stratford

London United Kingdom E20 1JQ 26/LO/0064 10.1186/ISRCTN16804705 362658 362658 Interventional Randomized controlled trial Open (masking not used) Active Parallel Treatment Feasibility of outdoor group psychological therapy Not applicable 2027-01-01T00:00:00.000Z United Kingdom England Birmingham and Solihull Mental Health NHS Foundation Trust

The Uffculme Centre 52 Queensbridge Road Moseley

Birmingham England B13 8QY RXT@2.16.840.1.113883.2.1.3.2.4.18.48 false Participants (service users) will be eligible to take part in the study if: 1. They are aged 18 years or above 2. They are currently receiving care from inpatient services at the Juniper Centre or Reservoir Court, Birmingham and Solihull NHS Foundation Trust 3. They are due to take part in a therapy group, such as Stressbusters 4. They have read the Participant Information Sheet and had the opportunity to speak to a researcher and ask any questions they may have about the study 5. There are no concerns about their capacity to provide informed consent to take part in the study 6. They provide informed consent by completing the Informed Consent Form Participants (staff) will be eligible to take part in the study if: 1. They are currently working in inpatient settings at the Juniper Centre or Reservoir Court, Birmingham and Solihull NHS Foundation Trust 2. They facilitate or co-facilitate groups, such as Stressbusters 3. They have read the Participant Information Sheet and had the opportunity to speak to a researcher and ask any questions they may have about the study 4. They provide informed consent by completing the Informed Consent Form Mixed 18 Years 120 Years All 24 0 Participants (service users) will be excluded from the study if: 1. They are not currently receiving inpatient care from the Juniper Centre or Reservoir Court, Birmingham and Solihull NHS Foundation Trust 2. They are not due to take part in a therapy group, such as Stressbusters 3. They are unable to understand the Participant Information Sheet or do not have the opportunity to speak with a researcher about the study 4. There are concerns about their capacity to provide informed consent to take part in the study 5. They do not provide informed consent by completing the Informed Consent Form Participants (staff) will be excluded from the study if: 1. They are not currently working in inpatient settings at the Juniper Centre or Reservoir Court 2. They do not facilitate or co-facilitate groups such as Stressbusters 3. They are unable to understand the Participant Information Sheet or do not have the opportunity to speak with a researcher about the study 4. They do not provide informed consent by completing the Informed Consent Form 2026-05-28T00:00:00.000Z 2026-09-17T00:00:00.000Z Psychological therapy for psychological distress in adults and older adults receiving inpatient mental health care for a range of mental health conditions and/or dementia Mental and Behavioural Disorders Intervention arm – outdoor Stressbusters group: Older adult inpatients due to attend the routinely offered Stressbusters therapy group will receive five weekly, one-hour group psychological therapy sessions delivered in an outdoor space on the ward. Each session focuses on one of the five senses (sight, hearing, taste, touch and smell) and provides strategies to reduce stress, using activities such as smelling lavender, looking at calming images or listening to uplifting music. Comparator arm – indoor Stressbusters group: Older adult inpatients will receive the same five weekly, one-hour Stressbusters group sessions, but delivered indoors. The content, frequency and duration of the therapy will be the same as in the outdoor arm, with the setting being the main difference between the two groups. Participants will be grouped according to the ward on which they are receiving inpatient care. Each ward-based group (cluster) will be randomly allocated to either the indoor or outdoor intervention. The study aims to recruit 16–24 participants across the four wards. Participants will complete questionnaires before and after the five-week intervention and at three-month follow-up. Brief feedback will also be collected after each session. Staff delivering the groups will complete questionnaires about their experience of delivering the therapy in the allocated setting. The study will assess the feasibility of recruitment, attendance and outcome measurement, as well as the acceptability and practicality of delivering Stressbusters indoors or outdoors. Randomisation Participants will be randomised by cluster according to the ward on which they are receiving inpatient care. Each cluster will comprise between 1 and 8 participants and will be randomised in a 1:1 ratio to receive the Stressbusters psychological therapy either indoors or outdoors. Block randomisation will be used to allocate clusters to the two study arms. An independent researcher, who is not involved in delivering the therapy, will conduct the randomisation using an Excel spreadsheet. Following randomisation, the researcher will inform the relevant therapy staff and service user participants whether the upcoming Stressbusters group will be delivered indoors or outdoors. The group will then be delivered in the allocated setting. Behavioural Not expected to be made available Protocol

0ed03880-a2d5-49e4-a6d9-03fa53e15d13 219fe7a6-e1c0-45b4-8338-30f536557b58 92656118-54cf-4bcf-b068-f88abfd36fc4 8d6af225-90e4-4a42-b9c6-f5fe3fd13343 dce9aedd-281c-4e28-bb73-288c21115807 No Participant information sheet 50104 Participant Information Sheet (Service User) v1.0 01Aug2025.pdf 45394494-5e85-478f-8d1c-39937f5b12cd true application/pdf 146239 3af1c3a85d45ec9bb5612e67209e5c80 Protocol file 50104 Protocol v1.0 01Aug2025.pdf b55bee6e-57bc-4e53-a6be-a2e75c5c94b5 true application/pdf 573139 ad91998e7c5c05128b5ab8bf78e050e9 Stephanie Howarth Principal investigator

University of Birmingham 52 Pritchatts Road, Edgbaston

Birmingham United Kingdom B15 2TT +44 121 414 3344 s.l.howarth@bham.ac.uk Public Anna Amiry https://orcid.org/0000-0002-0912-3387 Public

School of Psychology University of Birmingham 52 Pritchatts Road, Edgbaston

Birmingham United Kingdom B15 2TT +44 121 414 3344 axa2572@student.bham.ac.uk Public Carl Krynicki https://orcid.org/0000-0003-0943-5142 Scientific

School of Psychology University of Birmingham 52 Pritchatts Road, Edgbaston

Birmingham United Kingdom B15 2TT +44 121 414 3344 c.krynicki@bham.ac.uk Public University of Birmingham https://ror.org/03angcq70 Non-commercial Investigator initiated and funded 11648926 true A 6-week, double-blind, randomised controlled trial to assess the safety, tolerability and preliminary efficacy of a 5% SiPore-containing toothpaste AMYLO-STOP Tolerability Trial Primary objective: To assess the safety of twice-daily use of a 5% SiPore-containing toothpaste over 6 weeks, compared with a control toothpaste with the same base formula but without SiPore, in adults with mild-moderate gingival inflammation. Secondary safety and tolerability objectives: 1. To assess changes in plaque accumulation from baseline to 6 weeks 2. To assess changes in gingival inflammation from baseline to 6 weeks Exploratory objectives: 1. To collect saliva samples for analyses of the oral microbiome Background and study aims This study will look at the safety of a new toothpaste containing 5% SiPore and whether people are able to use it without unwanted effects. SiPore is a specially designed form of silica. Similar types of silica have previously been tested in people and have generally been found to be safe and well tolerated when taken by mouth.The main purpose of the study is to find out whether using toothpaste containing 5% SiPore causes any side effects, discomfort or irritation in the mouth. Who can participate? Adults aged 18 to 60 years with mild to moderate gum inflammation What does the study involve? Participants will be randomly placed into one of two groups. One group will use a toothpaste containing 5% SiPore and the other group will use a control toothpaste that looks, tastes and feels the same but does not contain SiPore. Participants will use their allocated toothpaste for 6 weeks. The study will also look at whether the toothpaste may have benefits for oral health. We will assess changes in the amount of dental plaque, gum inflammation and overall gum health. We will also look at the types of bacteria found in the mouth to see whether the toothpaste affects the balance of the oral bacterial community. What are the possible benefits and risks of participating? The results of this study will help us understand whether toothpaste containing 5% SiPore is suitable for wider use and will provide early information about whether it may have benefits for oral health. Where is the study run from? Birmingham Dental Hospital (UK) When is the study starting and how long is it expected to run for? September 2026 to December 2026 Who is funding the study? Orkla Health AS (Norway) Who is the main contact? Dr Praveen Sharma, p.sharma@bham.ac.uk The proportion of participants experiencing at least one serious treatment-emergent oral adverse event in the 5% SiPore and control toothpaste groups, a combination of clinical assessments (Turesky Plaque Index [TPI] for plaque accumulation, Modified Gingival Index [MGI] for gingival inflammation, assessment of oral hard and soft tissue conditions), participant-reported outcomes (including taste, texture, oral comfort and willingness to continue use), investigational product accountability records and biological sample collection. Data will be collected the baseline and 6-week timepoints by trained and calibrated study staff using standardised electronic case report forms (eCRFs). Participant-reported data will be collected using self-reported, questions such as 1) Would you switch from your current toothpaste to this toothpaste? 2) Would you recommend this toothpaste? 3) Do you feel cleaner after brushing with this toothpaste than with other toothpastes? Compliance data will be collected through participant self-report and return of used investigational product, with visual inspection of toothpaste tubes undertaken. Saliva samples will be collected according to a standardised sample collection procedure and used for exploratory oral microbiome analyses to investigate changes in oral microbiome with use of test or control toothpastes. Differences in any treatment-emergent oral adverse events including oral mucosal sloughing, oral ulceration, taste, texture, oral comfort and willingness to continue use between the test and the control toothpaste, a combination of clinical assessments (TPI for plaque accumulation, MGI for gingival inflammation, assessment of oral hard and soft tissue conditions), participant-reported outcomes (including taste, texture, oral comfort and willingness to continue use), investigational product accountability records and biological sample collection. Data will be collected the baseline and 6-week timepoints by trained and calibrated study staff using standardised electronic case report forms (eCRFs). Ethics approval required Wales Research Ethics Committee 5

Floor 4, Crown Building

Cardiff United Kingdom CF10 3NQ 26/WA/0215 10.1186/ISRCTN11648926 372427 372427 Interventional Randomized controlled trial Blinded (masking used) Active Parallel Treatment Not applicable 2026-12-11T00:00:00.000Z United Kingdom England Birmingham Dental Hospital

St. Chads Queensway

Birmingham England B4 6NN RYW21@2.16.840.1.113883.2.1.3.2.4.18.48 true 1. Aged 18 to 60 years, inclusive, at the time of screening 2. Able and willing to provide written informed consent 3. Willing and able to comply with all scheduled visits and all study procedures 4. In good general and mental health, with no condition that, in the opinion of the investigator or medically qualified designee, would: 4.1. Affect the participant’s safety or wellbeing 4.2. Affect the study outcomes 4.3. Or impair the participant’s ability to understand and follow study procedures and requirements 5. At screening, meeting all of the following oral health criteria 5.1. At least 20 natural permanent teeth, excluding third molars 5.2. Mild to moderate gingivitis defined as 10% ≤ BS ≤ 30% Adult 18 Years 60 Years All 80 0 1. Participation in another study involving investigational product(s), including non-medicinal studies, within 30 days before study entry or during participation 2. Any acute or chronic medical or psychiatric condition, serious or unstable condition, including cardiovascular disease, diabetes, liver or kidney disorder, that may increase risk, affect safety, interfere with study outcomes, or make participation inappropriate 3. Pregnant, intending to become pregnant during the study, or breastfeeding 4. Known or suspected intolerance or hypersensitivity to study materials, ingredients or related compounds 5. On a restricted carbohydrate or starch diet 6. Unwilling or unable to comply with protocol lifestyle considerations 7. Current smoker, current vaper, ex-smoker or ex-vaper who stopped within 6 months of screening, or user of smokeless tobacco, including chewing tobacco, gutkha, pan containing tobacco, or nicotine-based e-cigarettes 8. Medical condition or bleeding disorder that could influence gingival bleeding, study outcomes or participant safety 9. Severe oral conditions that could compromise study outcomes or participant/examiner safety 10. Tongue or lip piercing, or any other oral feature that could interfere with toothbrush use 11. Medication exclusions 11.1. Antibiotic medication within 28 days before screening or use during the study 11.2. Oral care product containing antibacterial agents, for example chlorhexidine, or any ingredient considered likely to affect plaque formation or gingival health within 4 weeks of screening 12. Periodontal exclusions: 12.1. Signs of periodontitis, defined as any site, not including wisdom teeth, with probing pocket depth ≥3.5 mm 12.2. Periodontal treatment within 12 months of screening 13. Dental exclusions: 13.1. Caries, restorations or dental conditions that could compromise outcomes or oral health 13.2. Partial or full dentures 13.3. Fixed orthodontic appliances or orthodontic treatment within 3 months of screening 13.4. Other orthodontic devices, including bands, fixed retainers or removable retainers, likely to interfere with study procedures, assessments or outcomes 13.5. Dental prophylaxis within 12 weeks of screening 13.6. Teeth bleaching within 12 weeks of screening 13.7. High levels of calculus deposits 13.8. Any other reason that, in the opinion of the study dentist or suitably qualified designee, makes participation inappropriate 2026-09-14T00:00:00.000Z 2026-09-25T00:00:00.000Z Mild-moderate gingival inflammation Oral Health Participants will be randomised in a 1:1 ratio to receive either the 5% SiPore-containing toothpaste or the control toothpaste with the same base formulation but without SiPore. Randomisation will occur at the baseline visit, once eligibility has been confirmed and all baseline assessments have been completed. Randomisation will be stratified by sex (male/female) and percentage of bleeding sites (<15% or ≥15%). The randomisation schedule will be generated using online, randomisation software. Allocation will be concealed until the point of assignment, using study product codes or an equivalent secure allocation system. Participants will be asked to use their allocated toothpaste twice daily for the duration of the study. Data and samples to assess primary and secondary outcomes will be collected at baseline and at the 6-week visit. Other Not expected to be made available 3cb88886-17d9-4cc4-8e2a-54399b9e1966 8908fcb4-da7b-4ad9-9d8d-7c04693a66dc 04d7c80d-8cb3-4d38-8868-cf130b04f4f0 No Praveen Sharma https://orcid.org/0000-0001-6435-4842 Public Scientific Principal investigator

Birmingham Dental Hospital 5 Mill Pool Way

Birmingham United Kingdom B5 7SA +44 (0)121 466 5128 p.sharma@bham.ac.uk Public Orkla (Norway) https://ror.org/04a839673 Commercial Orkla Health AS 14945909 true Evaluating nutritional ketosis versus NHS Eatwell guide for bipolar depression: single blind randomised controlled trial ENERGISE-BD To determine the efficacy of nutritional ketosis in comparison to the NHS EatWell guide (9) for the treatment of bipolar depression. Background and study aims Bipolar disorder is a mental health condition which causes repeated episodes of low and high mood. Many people with bipolar disorder also experience long-lasting symptoms of depression, which can significantly affect everyday life. The current understanding of how bipolar disorder develops remains unclear, and treatments for the depressive symptoms are not always effective and often have unwanted side effects. Some evidence suggests that changes in diet might help treat depressive symptoms in bipolar disorder, so we are doing this study to investigate this further. We think certain diets could reduce feelings of depression, and want to know if this is something doctors should recommend in the future. Who can participate? Male and female adults (18+ years old) with a diagnosis of bipolar disorder and are currently experiencing bipolar depression. What does the study involve? We want to compare the NHS EatWell Guide to nutritional ketosis. The NHS EatWell Guide recommends eating a variety of foods for a balanced diet. Nutritional ketosis is achieved by following a ‘keto’ diet, which is high in fat and very low in carbohydrates, allowing the body to switch to burning fat for energy. In this study, one group of people follow the nutritional ketosis plan for 12 weeks and the other group follow the NHS EatWell Guide for 12 weeks. • There is an equal chance of going into each group. We aim to recruit 206 people in total (103 people in each group). • Participants will know which group they go into. • We will study how each group gets on to see which one is the most effective as a treatment for bipolar depression. • We will take the following measurements: • Height, weight and blood pressure • Blood glucose/ketones • Blood sample to assess different markers of physical health • Urine test to check if pregnant (if relevant) • A series of questionnaires, which will ask about the participants mental health and physical health • Some of the participants in the study who are based in Edinburgh will undergo a Magnetic Resonance Spectroscopy scan of the brain. What are the possible benefits and risks of participating? Potential benefits of taking part in this study include: • Learning more about your mental health and mood over the time you spend in the study, and how they relate to changes in your diet. • Education and advice on a dietary intervention from a qualified dietitian. • The results from this study may help us to improve treatments for people with bipolar depression in the future, and your participation could make a meaningful impact on this important area of research. • We will reimburse participants for their time and travel expenses. The disadvantages are that participants may find the study time-consuming, as it will last 24 weeks and require you to attend 3 to 4 face-to-face appointments depending on whether they are one of the participants who will undergo brain scans (Magnetic Resonance Spectroscopy). Appointments will include questionnaires which may take some time and ask sensitive questions about the participants personal and mental health history, which some participants may find upsetting. Dietary changes may cause side effects including stomach upset, nausea, vomiting, changes in bowel habits (particularly constipation), hunger, thirst, tiredness, irritability, weight loss, low blood sugar (hypoglycaemia), high levels of fat in the blood (hyperlipidaemia), high levels of ketones in the blood, leg cramps, or irregular periods in women. As nutritional ketosis involves eating a high proportion of fat, it may increase levels of fat in the blood (cholesterol and triglycerides). Blood tests may be uncomfortable or upsetting, and they may cause small bruises. There is a small chance that blood tests or brain scans might find unexpected abnormalities. A minority of people find Magnetic Resonance Spectroscopy brain scans anxiety-provoking and may experience a fear of small spaces (claustrophobia) during the scans. Where is the study run from? The University of Edinburgh and NHS Lothian (UK) When is the study starting and how long is it expected to run for? October 2026 to July 2030 Who is funding the study? Wellcome Trust (UK) Who is the main contact? Lorna Dewar energise-bd.trial@ed.ac.uk Proportion of participants in each arm who experience a clinically meaningful response, defined as a drop in PHQ-9 score of 6 or more Patient Health Questionnaire (PHQ-9) baseline and 12 week post randomisation 1. Severity of depression symptoms measured using the Patient Health Questionnaire-9 (PHQ-9) at baseline, 12 weeks and 24 weeks post randomisation 2. Anxiety symptoms measured using the Generalised Anxiety Disorder Questionnaire (GAD-7) at baseline, 12 weeks and 24 weeks post randomisation 3. Mania symptoms measured using the Altman Self-Rating Mania Scale (ASRM) at baseline, 12 weeks and 24 weeks post randomisation 4. Health-related quality of life measured using the EuroQol EQ-5D-5L at baseline, 12 weeks and 24 weeks post randomisation 5. Functional impairment measured using the Functioning Assessment Short Test (FAST) at baseline, 12 weeks and 24 weeks post randomisation 6. Concurrent medication use (psychiatric and other medications) measured using study-recorded medication data at baseline, 12 weeks and 24 weeks post randomisation 7. Continuation of allocated diet intervention measured using study-recorded intervention adherence data at baseline, 12 weeks and 24 weeks post randomisation 8. Feasibility of collecting health economic resource use consequences and associated costs of a nutritional ketosis intervention compared to the NHS EatWell Guide for bipolar depression measured using a bespoke health economic resource use questionnaire at 12 weeks and 24 weeks post randomisation 9. Body mass index (BMI) measured using BMI calculated from measured height and weight at baseline and 12 weeks post randomisation 10. Weight change from baseline (percentage) measured using percentage change in body weight calculated from measured weight at baseline and 12 weeks post randomisation 11. Blood pressure (BP) measured using blood pressure measurement at baseline and 12 weeks post randomisation 12. Glycated haemoglobin (HbA1c) measured using an HbA1c blood test at baseline and 12 weeks post randomisation 13. Insulin resistance (C-peptide and glucose) measured using blood tests for C-peptide and glucose at baseline and 12 weeks post randomisation 14. Lipid profile (total cholesterol, triglycerides, cholesterol/HDL ratio and non-HDL cholesterol) measured using a lipid profile blood test at baseline and 12 weeks post randomisation 15. Renal function (urea and electrolytes [U&Es]) measured using a urea and electrolytes blood test at baseline and 12 weeks post randomisation 16. Liver function measured using liver function tests (LFTs) at baseline and 12 weeks post randomisation 17. Plasma lactate measured using a plasma lactate blood test at baseline and 12 weeks post randomisation 18. Blood ketone levels measured using a KetoMojo device daily from baseline to 12 weeks post randomisation 19. Blood glucose levels measured using a KetoMojo device daily from baseline to 12 weeks post randomisation 20. Magnetic Resonance Spectroscopy (MRS) markers of brain energetics: Estimated molal tissue concentration of glutamate plus glutamine (Glx), and lactate (Lac), phosphocreatine/ATP signal ratio and intracellular pH measured using Magnetic Resonance Spectroscopy (MRS) assessments of brain metabolites at baseline, 6 weeks and 12 weeks post randomisation Ethics approval required East Midlands – Leicester South Research Ethics Committee

Health Research Authority 3 Piccadilly Place London Road Manchester

Manchester United Kingdom M1 3BN 26/EM/0140 10.1186/ISRCTN14945909 370428 CPMS: 76325 370428 76325 Interventional Randomized controlled trial Blinded (masking used) Active Parallel Treatment Not applicable 2030-07-01T00:00:00.000Z United Kingdom England Scotland 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 The Barberry

25 Vincent Drive

Birmingham England B15 2FG RXT@2.16.840.1.113883.2.1.3.2.4.18.48 false 1. Adults (aged 18 and over) with a primary* diagnosis of bipolar disorder (BD-I or BD-II), confirmed by the Structured Clinical Interview for DSM5 (Diagnostic and Statistical Manual of Mental Disorders, fifth edition), (SCID5) 2. Bipolar depression symptoms of at least moderate clinical severity on the PHQ-9 (defined as a score of 10 or above) *Other comorbid psychiatric diagnoses are permitted (apart from eating disorders and substance misuse/dependence) Mixed 18 Years 100 Years All 206 0 Current key exclusion criteria as of 11/08/2026: 1. Currently in need of acute inpatient, crisis resolution, or home treatment services 2. Does not have capacity to consent 3. Previous use of nutritional ketosis within 2 months 4. Current use of weight loss medications (such as semaglutide or tirzepatide) 5. Inability to complete mandatory study assessments 6. No access to a smartphone and/or unwilling to add the KetoMojo app to their smartphone 7. Specific contraindications for the nutritional ketosis intervention: 7.1. Pregnancy, breastfeeding, or planning to become pregnant within 3 months 7.2. Liver failure 7.3. Pancreatitis (acute and past history) 7.4. Chronic kidney disease 7.5. Type I diabetes 7.6. Use of SGLT-2 inhibitors 7.7. Recent stroke or myocardial infarction 7.8. Heart failure 7.9. Cardiac arrhythmias 7.10. Respiratory failure 7.11. Active infections 7.12. Cancer 7.13. Hyperuricaemia 7.14. Severe hyperlipidaemia (familial hypercholesterolaemia, severe hypertriglyceridemia, or a documented medical history of high total cholesterol >7.5 mmol/L) 7.15. Participant-reported inborn error of metabolism affecting fatty acid transport/oxidation, including organic acidurias and mitochondrial fatty acid beta-oxidation disorders 8. Past history of an eating disorder (bulimia or anorexia) 9. Currently only eating a vegan or exclusively plant-based diet 10. Other major primary psychiatric disorder that is not bipolar disorder, or major neurological disorders 11. Harmful current use of or dependence on psychoactive substances (including alcohol) 12. Currently enrolled in an interventional research study _____ Previous key exclusion criteria: 1. Currently in need of acute inpatient, crisis resolution, or home treatment services 2. Does not have capacity to consent 3. Previous use of nutritional ketosis within 2 months 4. Current use of weight loss medications (such as semaglutide or tirzepatide) 5. Inability to complete mandatory study assessments 6. No access to a smartphone and/or unwilling to add the KetoMojo app to their smartphone 7. Specific contraindications for the nutritional ketosis intervention: 7.1. Pregnancy, breastfeeding, or planning to become pregnant within 3 months 7.2. Liver failure 7.3. Pancreatitis (acute and past history) 7.4. Chronic kidney disease 7.5. Type I diabetes 7.6. Use of SGLT-2 inhibitors 7.7. Recent stroke or myocardial infarction 7.8. Heart failure 7.9. Cardiac arrhythmias 7.10. Respiratory failure 7.11. Active infections 7.12. Cancer 7.13. Hyperuricaemia 7.14. Severe hyperlipidaemia (familial hypercholesterolaemia, severe hypertriglyceridaemia, or total cholesterol >7.5 mmol/L) 7.15. Participant-reported inborn error of metabolism affecting fatty acid transport/oxidation, including organic acidurias and mitochondrial fatty acid beta-oxidation disorders 8. Past history of an eating disorder (bulimia or anorexia) 9. Currently only eating a vegan or exclusively plant-based diet 10. Other major primary psychiatric disorder that is not bipolar disorder, or major neurological disorders 11. Harmful current use of or dependence on psychoactive substances (including alcohol) 12. Currently enrolled in an interventional research study 2026-10-01T00:00:00.000Z 2029-12-01T00:00:00.000Z Bipolar depression Mental and Behavioural Disorders ENERGISE-BD is a single blind randomised controlled trial of nutritional ketosis versus the NHS EatWell guide for the treatment of bipolar depression. Participants will be randomised in a 1:1 ratio to either the nutritional ketosis intervention or the NHS EatWell Guide control group using a secure online randomisation system designed and managed by the Edinburgh Clinical Trials Unit (ECTU). Nutritional ketosis intervention: Participants will follow a modified ketogenic diet for 12 weeks, providing approximately 60–75% of estimated energy requirements from fat, 5–7% from carbohydrates, with the remaining energy provided by protein. For the first two weeks pre-prepared meals will provide the required daily calorie and macronutrient composition and will be tailored to individual dietary requirements. NHS EatWell Guide control: Participants will follow a diet based on the NHS EatWell Guide for 12 weeks, which promotes a healthy, balanced diet comprising fruit and vegetables, starchy carbohydrates, lean sources of protein, dairy or suitable alternatives, and healthy fats, with smaller amounts of foods high in fat, salt and sugar. The allocated dietary intervention will last for 12 weeks. Participants will attend in-person study visits at baseline, 6 weeks and 12 weeks. During the 12-week intervention, participants in both groups will have weekly remote contact with a study dietitian to provide dietary support and monitor adherence to their allocated diet. At the end of the 12-week intervention, participants will be supported during a 2-week phase-out from their allocated diet. A final follow-up appointment will be conducted remotely at 24 weeks. Brain imaging substudy: At the Edinburgh site, approximately 72 eligible participants without contraindications to magnetic resonance (MR) scanning (approximately 36 from each treatment arm) will undergo 1-hour 3T MR scans at baseline, 6 weeks and 12 weeks. Imaging will include anatomical brain imaging for the detection of incidental pathology and positioning of magnetic resonance spectroscopy (MRS) volumes of interest. Other The datasets generated during and/or analysed during the current study will be stored in a publicly available repository: Edinburgh DataShare. Following publication of the primary study results, anticipated approximately 9–12 months after the end of the project, de-identified participant-level data, together with relevant supporting metadata and documentation, will be made available via Edinburgh DataShare for secondary research purposes. Data will remain available in accordance with the repository’s preservation and access policies. Imaging data, including images and spectra, are potentially re-identifiable and will therefore be stored securely on University of Edinburgh servers rather than in a publicly accessible repository. Requests to access these data, or for other data-sharing activities not specified in the protocol, will be reviewed in accordance with ECTU data-sharing procedures. Access will be subject to participant consent and applicable ethical, legal and information governance requirements. Requests will be assessed according to factors including the proposed purpose and scientific merit, suitability of the requester, data requested and risk of re-identification. Where approved, the minimum necessary data will be shared in the least identifiable form using an appropriately secure mechanism and subject to any required agreements. Stored in publicly available repository f184ff95-1834-4693-81ef-5d91924e8b47 e4d03f9a-cab6-4e96-83c5-3cdbc6ada87e 2f53fb96-79d3-4a97-b840-7c03b0c5d75a 1db7987c-e1cc-4be2-bec7-fca508605d13 4f8d7c5b-26d2-48c5-89fa-9dcc6be86c7e cfa467ba-8d80-4c85-b208-0f329498a11f Yes Daniel Smith https://orcid.org/0000-0002-2267-1951 Principal investigator Scientific

The Royal Infirmary of Edinburgh 51 Little France Crescent Old Dalkeith Road Edinburgh

Edinburgh United Kingdom EH16 4SA +44 7734463270 d.smith@ed.ac.uk Public Steven Marwaha https://orcid.org/0000-0002-0303-9942 Principal investigator Scientific

Birmingham and Solihull Mental NHS Foundation Trust

Birmingham United Kingdom B13 8QY - s.marwaha@bham.ac.uk Public Lorna Dewar https://orcid.org/0009-0009-7260-4165 Public

ECTU, Usher Building The University of Edinburgh Edinburgh BioQuarter 5-7 Little France Road

Edinburgh United Kingdom EH16 4UX - energise-bd.trial@ed.ac.uk Public Rebecca Reynolds https://orcid.org/0000-0001-6226-8270 Scientific

The Royal Infirmary of Edinburgh 51 Little France Crescent Old Dalkeith Road Edinburgh

Edinburgh United Kingdom EH16 4SA - r.reynolds@ed.ac.uk Public University of Edinburgh and NHS Lothian Non-commercial Wellcome http://dx.doi.org/10.13039/100004440 30583116 true oPtimising post-dischArge care pathways after acute paNcreatitis: evaluatiOn of health seRvice utilisAtion, outcoMes PANORAMA 1. Develop conceptual framework for a ‘gold-standard’ post-hospital discharge pathway (WP1) 2. Explore patient experience of post-hospital discharge care (WP2) 3. Explore clinician approaches to post-discharge care (WP3) 4. Describe real-world pathways experienced by patients after hospital discharge (WP4) 5. Identify groups at highest risk of use of health care services (WP2&4) 6. Co-produce interventions for post-discharge care pathways (WP5) Background and study aims Acute pancreatitis is a common condition that causes inflammation of the pancreas and leads to thousands of hospital admissions in the UK each year. Although most people recover enough to leave hospital, many continue to experience health problems after discharge. These can include difficulties with digestion, problems controlling blood sugar, anxiety, depression, and ongoing pain. Some people also return to hospital after they have been discharged. At present, there is no standard approach to follow-up care after acute pancreatitis in the UK. The PANORAMA study aims to understand what support people need after leaving hospital, how current care pathways are working, and how care could be improved. The researchers also want to identify which patients are most likely to need additional support or further healthcare after discharge. Findings from the study will be used to develop recommendations for future care pathways. Who can participate? Different parts of the study involve different groups of people: 1. People aged 16 years or over who have experienced acute pancreatitis and received care through the NHS 2. Family members or carers of people who have experienced acute pancreatitis 3. Healthcare professionals involved in caring for patients with acute pancreatitis, including hospital doctors, specialist nurses, allied health professionals and GPs 4. Patients currently in hospital with acute pancreatitis who are due to be discharged and are able to give informed consent The study is recruiting participants from across the United Kingdom. What does the study involve? The study is made up of five linked work packages (WP). In WP1, patients, carers and healthcare professionals will be invited to complete a survey about their experiences and views of care after discharge from hospital. In WP2, some patients and carers will be invited to take part in a virtual interview lasting up to 1 hour. Participants will discuss their experiences after leaving hospital and describe what they think could improve care. In WP3, healthcare professionals will take part in similar interviews to explore their experiences of supporting patients after acute pancreatitis and their views on how care could be improved. In WP4, patients who are about to be discharged from hospital after acute pancreatitis will be asked to complete questionnaires about their quality of life, mental health, digestive health and healthcare use. These questionnaires will be completed at discharge and then again after 7 days, 28 days, 3 months and 6 months. Each questionnaire session may take up to 30 minutes. In WP5, selected patients, carers and healthcare professionals will be invited to attend a workshop to discuss the study findings and help develop recommendations for improving care after acute pancreatitis. What are the possible benefits and risks of participating? Participants may not receive any direct medical benefit from taking part. However, their experiences and opinions could help researchers understand how care after acute pancreatitis can be improved. The findings may help shape future services and support for patients recovering from this condition. The risks of participation are expected to be low. Some people may find it upsetting to discuss their experiences of illness during interviews. If a participant becomes distressed, the interview can be paused or stopped, and information about support services can be provided. Participants in the questionnaire study who report signs of severe mental distress or risk of self-harm will be advised to seek help from NHS 111 or their GP. Where is the study run from? The study is sponsored and led by the University of Birmingham and is being conducted in collaboration with NHS hospitals across England and Scotland. Participant data will be managed through secure systems hosted by the University of Birmingham. When is the study starting and how long is it expected to run for? July 2026 to September 2027. Who is funding the study? The study is funded by the National Institute for Health and Care Research (NIHR). Who is the main contact? Dr Michala Pettitt panorama-study@contacts.bham.ac.uk> WP1: Identification of the opportunities that exist to improve care after discharge from hospital following acute pancreatitis survey of stakeholders to identify the key features and characteristics that define a ‘good’ follow-up pathway for patients with AP. Qualitative content analysis using a thematic approach until saturation is reached (40 patients/ carers, 40 clinicians) WP2: Commentary describing the experiences of participants (patients and their carers) following discharge from hospital with acute pancreatitis purposive selection of candidates completing an EoI to maximise sampling across collected descriptors (sex, ethnicity, aetiology, region), followed by semi-structure interviews (informed by analysis of WP1) and qualitative thematic analysis Following analysis of WP1 to run concurrently with WP3 and WP4 WP3: Commentary describing the experiences of NHS clinicians with responsibilities for the care of patients with AP purposive selection of candidates completing an EoI to maximise sampling across collected descriptors (sex, ethnicity, aetiology, region), followed by semi-structure interviews (informed by analysis of WP1) and qualitative thematic analysis following analysis of WP1 to run concurrently with WP2 and WP4 WP4: Patient demographics, Patient co-morbidities, Prior diagnosis of mental health issues, Disease aetiology and inpatient treatment, Clinician planned follow-up on discharge patient records baseline WP4: Alcohol usage AUDIT-C PROM baseline WP4: Patient quality of life EQ-5D-5L PROM discharge, 7 days, 30 days, 3 months, 6 months WP4: Patient anxiety GAD-7 PROM discharge, 7 days, 30 days, 3 months, 6 months WP4: Patient depression PHQ-9 PROM discharge, 7 days, 30 days, 3 months, 6 months WP4: Patient endocrine insufficiency score PEI-Q PROM discharge, 7 days, 30 days, 3 months, 6 months WP4: Healthcare utilisation following discharge Healthcare Utilisation PROM 30 days, 3 months, 6 months WP5: Identification of opportunities to implement the findings from WP1-4 data from WP1-4 will be triangulated to identify commonalities and differences. These analyses will form the basis of discussions in a one-day stakeholder workshop. Rolfe’s Co-reflective model ‘What?, So What?, Now What?’ will be used as a framework to identify opportunities to amend post-discharge pathways for patients following hospitalisation with acute pancreatitis the end of analysis of preceding WP1-4 Ethics approval required South Central - Oxford B Research Ethics Committee

2 Redman Place, Stratford

London United Kingdom E20 1JQ 26/SC/0148 10.1186/ISRCTN30583116 349680 CPMS: 64883, NIHR: 165210 349680 64883 165210 Observational Cohort study Treatment 2027-09-30T00:00:00.000Z United Kingdom England Scotland University Hospitals Birmingham NHS Foundation Trust

Queen Elizabeth Hospital Mindelsohn Way Edgbaston

Birmingham England B15 2GW RRK@2.16.840.1.113883.2.1.3.2.4.18.48 Somerset NHS Foundation Trust

Trust Management Lydeard House Musgrove Park Hospital

Taunton England TA1 5DA RH5@2.16.840.1.113883.2.1.3.2.4.18.48 Leeds Teaching Hospitals NHS Trust

St. James's University Hospital Beckett Street

Leeds England LS9 7TF RR8@2.16.840.1.113883.2.1.3.2.4.18.48 Manchester University NHS Foundation Trust

Cobbett House Oxford Road

Manchester England M13 9WL R0A@2.16.840.1.113883.2.1.3.2.4.18.48 York and Scarborough Teaching Hospitals NHS Foundation Trust

York Hospital Wigginton Road

York England YO31 8HE RCB@2.16.840.1.113883.2.1.3.2.4.18.48 Liverpool University Hospitals NHS Foundation Trust

Royal Liverpool University Hospital Prescot Street

Liverpool England L7 8XP REM@2.16.840.1.113883.2.1.3.2.4.18.48 Oxford University Hospitals NHS Foundation Trust

John Radcliffe Hospital Headley Way Headington

Oxford England OX3 9DU RTH@2.16.840.1.113883.2.1.3.2.4.18.48 NHS Lothian

Waverley Gate 2-4 Waterloo Place

Edinburgh Scotland EH1 3EG SS999@2.16.840.1.113883.2.1.3.8.2.16.1 South Warwickshire University NHS Foundation Trust

Warwick Hospital Lakin Road

Warwick England CV34 5BW RJC@2.16.840.1.113883.2.1.3.2.4.18.48 University Hospitals Bristol and Weston NHS Foundation Trust

Trust Headquarters Marlborough Street

Bristol England BS1 3NU RA7@2.16.840.1.113883.2.1.3.2.4.18.48 Nottingham University Hospitals NHS Trust

Trust Headquarters Queens Medical Centre Derby Road

Nottingham England NG7 2UH RX1@2.16.840.1.113883.2.1.3.2.4.18.48 Maidstone and Tunbridge Wells NHS Trust

The Maidstone Hospital Hermitage Lane

Maidstone England ME16 9QQ RWF@2.16.840.1.113883.2.1.3.2.4.18.48 Gloucestershire Hospitals NHS Foundation Trust

Cheltenham General Hospital Sandford Road

Cheltenham England GL53 7AN RTE@2.16.840.1.113883.2.1.3.2.4.18.48 Torbay and South Devon NHS Foundation Trust

Torbay Hospital Newton Road

Torquay England TQ2 7AA RA9@2.16.840.1.113883.2.1.3.2.4.18.48 Greater Glasgow and Clyde

Gartnavel Royal Hospital 1055 Great Western Road

Glasgow Scotland G12 0XH SG9@2.16.840.1.113883.2.1.3.2.4.18.48 North Bristol NHS Trust

Southmead Hospital Southmead Road Westbury-on-trym

Bristol England BS10 5NB RVJ@2.16.840.1.113883.2.1.3.2.4.18.48 University Hospitals of North Midlands NHS Trust

Newcastle Road

Stoke-on-trent England ST4 6QG RJE@2.16.840.1.113883.2.1.3.2.4.18.48 University Hospitals of Derby and Burton NHS Foundation Trust

Royal Derby Hospital Uttoxeter Road

Derby England DE22 3NE RTG@2.16.840.1.113883.2.1.3.2.4.18.48 Forth Valley

Carseview House Castle Business Park

Stirling Scotland FK9 4TS SV9@2.16.840.1.113883.2.1.3.2.4.18.48 The Shrewsbury and Telford Hospital NHS Trust

Mytton Oak Road

Shrewsbury England SY3 8XQ RXW@2.16.840.1.113883.2.1.3.2.4.18.48 NHS Grampian

Summerfield House 2 Eday Road

Aberdeen Scotland AB15 6RE SN999@2.16.840.1.113883.2.1.3.8.2.16.1 false WP1: Any lived experience of adult acute pancreatitis care in NHS as patient or carer, clinician providing NHS care to patients with acute pancreatitis in secondary or primary care. WP2: Adults (or their carers) with experience of acute pancreatitis care in the NHS within the preceeding six months. Ideally have a conversational standard of English, but translation can be arranged. WP3: Clinicians (surgeons, gastroenterologists, specialist nurses, allied health professionals, GPs) providing NHS care to patients with acute pancreatitis. WP4: People currently admitted to hospital for acute pancreatitis who are due to be discharged. Must be able to consent to participate. WP5: Any lived experience of adult acute pancreatitis care in NHS as patient or carer, clinician providing NHS care to patients with acute pancreatitis in secondary or primary care. Minimum age of participants in any work stream is 16 years old, and participants may be up to 100 years old. Mixed 16 Years 100 Years All 1017 0 WP1: Must be able to complete survey in English WP2: Must have experienced care as an adult WP3: Non UK clinical practice WP4: Unwilling to consent; no capacity to consent 2026-06-17T00:00:00.000Z 2027-09-30T00:00:00.000Z Acute pancreatitis Digestive System There are 5 Work Packages (WP). These are complementary and intended to inform aspects of the final WP5 (see study summary graphic). WP1: Survey In order to ensure that themes addressed in the interviews cover all relevant aspects of post discharge care, we will undertake a short initial survey. This will recruit 20-40 from each group of patients/carers, secondary care clinicians (surgeons/gastroenterologists), nursing and allied health professionals, and general practitioners. The survey captures key demographic data, and asks participants to consider what opportunities exist to improve care after discharge, up to 6 months after acute pancreatitis. WP2: Patient interviews A topic guide has been prepared and will be refined with information from WP1. We will invite people with lived experience of acute pancreatitis to take part in a virtual interview of up to an hour. People can register an interest in participation following links from posts on social media and through interest groups, charities, and the NIHR Be Part of Research registry. They will be asked to complete a short expression of interest form. The research team will review expressions of interest and aim to recruit people with a range of experiences by looking at age, gender, ethnicity, geographical region, and whether pancreatitis was related to gallstones. When an appropriate participant is found, they will be contacted and the study further discussed with them. Should they wish to proceed, a digital consent form will be completed and a meeting arranged. The meeting will be conducted by a non clinical, experience qualitative researcher, and will be conducted by virtual meeting. The interview will explore experience of post-discharge care after pancreatitis, and what the participant feels might improve this. Should the participant become distressed, the interview will be paused, and terminated if necessary. Signposting to resources such as charities will be undertaken. Participation is complete at the end of the interview. The recording will be transcribed, and then dual coded by two researchers. A theoretical framework of post discharge needs will be developed using a thematic analysis approach. This will provide the patient perspective on post-discharge care. WP3: Clinician interviews A topic guide has been prepared and will be refined with information from WP1. We will invite clinicians who care for people with acute pancreatitis to take part. People can register an interest in participation following links from posts on social media and emails through specialist clinical associations. They will be asked to complete a short expression of interest form. The research team will review expressions of interest and aim to recruit people with a range of experiences by looking at clinical role, and geographical region. When an appropriate participant is found, they will be contacted and the study further discussed with them. Should they wish to proceed, a digital consent form will be completed and a meeting arranged. The meeting will be conducted by a non clinical, experience qualitative researcher, and will be conducted by virtual meeting. The interview will explore experience of post-discharge care after pancreatitis, and what opportunities there are to improve this. This will explore ideas around clinical reasoning and assessment of disease and patient recovery. Participation is complete at the end of the interview. The recording will be transcribed, and then dual coded by two researchers. A theoretical framework of post pancreatitis health risks and pathway opportunities will be developed. This will provide insight into clinical reasoning and priorities. WP4: Cohort study This will recruit people who are due to be discharged from hospital following an episode of acute pancreatitis drawing from several hospitals around the UK. Participants can be approached during their recovery and recruited up to the day of hospital discharge. This is supported by posters in the clinical area, a participant information sheet, and a short video. If a participant consents, they will complete a set of questionnaires on the day of discharge. These relate to quality of life, mental health, and impact of disease on digestion. These are repeated at day 7, 28, 3 months, and 6 months. There is an additional questionnaire about alcohol use at baseline. We will ask about health service use at 28 days, 3 months, and 6 months post discharge. Participants will receive reminders to complete by email, sms, or post. All post discharge contact is with the central research team. The questionnaires may take up to 30 minutes to complete. If a participant reponds to mental health questionnaires indicating high risk of self harm, they will be contacted and advised to seek help via 111 or their GP. This WP will provide data on health utilisation in the 6 months following discharge. It will provide novel data on the development of anxiety or depression, general quality of life, and patient reported symptoms of pancreatic exocrine insufficiency. We will use these data to construct models to allow us to stratify people who are most likely to use health care services following acute pancreatitis. WP5: Implementation workshop People who have shown interest in participation in previous WP will be invited to express interest in participating in a workshop to discuss the findings of the study. We will use purposive sampling to identify those to invite to the workshop. A PIS will be provided to those selected to participate, and consent secured. This will continue until we have a minimum of 20 participants, 10 of whom are patients or carers, and the remainder a mix of health care professionals with roles in care of acute pancreatitis. We will present the findings of the study to the whole group. We will then break off into smaller groups to discuss key themes. It is not yet clear what these are, but they may include dietary intervention, mental health support, stratified follow-up, pain management. Smaller groups of 4-5 participants includind patients and clinicians will discuss a single theme. A facilitator will lead this, using a 'so what, now what' framework. This will encourage reflection, contextualising findings, and encouraging participants to share ideas on how to address these challenges. We will take fields notes on the discussions and compile a list of 'recommendations to change practice' and 'recommendations for further research'. These ideas and reflections will be presented back to the wider group for comment. We will share this list with policymakers, clinicians, patients, and researchers to influence future care. Data will be held on secure servers. Expression of interest and cohort data including PROMS will be captured on REDCap hosted at the University of Birmingham. This is encrypted and password protected, using two factor authentication. Other Data sharing statement to be made available at a later date Protocol

WP2 (Carer)

WP2 (Patient)

WP3 (Healthcare)

WP4

WP5 (Carer)

WP5 (Healthcare)

WP5 (Patient)

a8302537-1fc8-48d8-bf9b-8017a0a1efa7 45a86941-ef30-4088-9da9-fc9a6a7ec9e6 4139f118-08af-43cf-b57e-17f39dd608da a99f577c-dde0-44d1-bfda-2b0d5029b807 No WP2 (Carer) 49694 PANORAMA WP2 - PIS (Carer) v1.1 (11-May-2026).pdf b48a81a5-d3ce-4331-aaaa-6646e60da2c1 true application/pdf 248523 0c2c4fce06c569ab0039972ad46c69fe WP2 (Patient) 49694 PANORAMA WP2 - PIS (Patient) v1.1 (11-May-2026).pdf a63d6196-1b78-491d-b4ef-7ad6d6509732 true application/pdf 247988 86bc26aef761125d83fa7228ae598af0 WP3 (Healthcare) 49694 PANORAMA WP3 – Healthcare PIS v1.1 (11-May-2026).pdf 02eea570-22d3-4672-860a-8cb32432bd6b true application/pdf 253412 3ebf145b4440746a8ae06733c7764f3b WP4 49694 PANORAMA WP4 - Participant Information Sheet v1.1 (11-May-2026).pdf cfc4980b-08c2-441e-aac5-bb5219f4839a true application/pdf 250114 ef709faad49a914d4bcf913e4b0b8b69 WP5 (Healthcare) 49694 PANORAMA WP5 – Healthcare PIS v1.1 (11-May-2026).pdf 6a625896-ebb4-4e20-b995-e0bc91f924f8 true application/pdf 260109 cfec9b3b67e8c1ec5e6999c60d96c23d WP5 (Carer) 49694 PANORAMA WP5 - Participant Information Sheet (Carer) v1.1 (11-May-2026).pdf d3ba6b4f-65ec-47eb-9025-005344c01869 true application/pdf 257031 edda5912aa2bbb878b1cce268a8123b2 WP5 (Patient) 49694 PANORAMA WP5 - Participant Information Sheet (Patient) v1.1 (11-May-2026).pdf b01b09f5-7cea-4a8f-bddb-15f3375ce1a8 true application/pdf 255957 e5a8194c9a60351c48a8141029509917 Protocol file 49694 PANORAMA PROTOCOL v1.1 (11-May-2026).pdf 140b17b8-7b62-4c82-b570-191a56b5aaa3 true application/pdf 1274826 7d45197443eb0e6122b78f0d75c18bdd Michala Pettitt https://orcid.org/0000-0002-4736-259X Public Scientific

Public Health Building University of Birmingham

Birmingham United Kingdom B15 2TT +44 121 415 9106 panorama-study@contacts.bham.ac.uk Public Matt Lee https://orcid.org/0000-0001-9971-1635 Principal investigator

Public Health Building University of Birmingham

Birmingham United Kingdom B15 2TT - m.j.lee.1@bham.ac.uk Public University of Birmingham University/education https://ror.org/03angcq70 Non-commercial National Institute for Health and Care Research http://dx.doi.org/10.13039/501100000272 17096714 true Developing a patient-physician co-created national diabetes-related emergencies management monitoring model DEKODE 1. To determine variations and inequalities in diabetes-related emergencies care outcomes in the UK across age, sex, ethnicity, deprivation, region, and vulnerable populations 2. To understand the experiences of people and their carers who have been treated for diabetes-related emergencies 3. To identify implementation principles for patient-centred care in people admitted with diabetes-related emergencies and through DEKODE 4. To investigate the predictors, clinical outcomes, and healthcare impact of recurrent diabetes-related emergencies episodes 5. To evaluate the cost-effectiveness of the DEKODE initiative Background and study aims Diabetic ketoacidosis (DKA) is a dangerous condition where the body lacks enough insulin, causing high blood sugar and acid levels. It's one of the most common reasons people with diabetes need emergency hospital care, with over 32,000 UK cases last year costing the NHS more than £90 million. If untreated, DKA can be life-threatening. In 2020, researchers developed DEKODE, a digital tool helping hospitals track and improve DKA care. Early results showed care varies widely, even within the same hospital, but the reasons are unclear, and patient views haven't been captured. This study aims to understand why DKA care varies across the UK, explore patient and staff experiences, improve the DEKODE tool, investigate repeat DKA episodes, and assess whether DEKODE saves the NHS money Who can participate? 1. Patients admitted to hospital with DKA (using anonymised hospital records from 2001 onwards) 2. Patients aged 16-99 years recently treated for DKA at University Hospitals Birmingham, and their carers 3. Healthcare professionals involved in DKA care at hospitals using DEKODE across the UK What does the study involve? The study has five parts: analysing anonymised NHS hospital records to see how DKA rates and outcomes differ by age, sex, ethnicity, deprivation and region; inviting patients, carers and staff to complete questionnaires and optional video interviews about their experiences; interviewing staff at hospitals using DEKODE to understand what helps or hinders its use; studying hospital data on people who've had DKA more than once; and calculating NHS treatment costs and whether DEKODE reduces them over time. No new treatments are tested – the study focuses on experiences, care patterns and costs. What are the possible benefits and risks of participating? The risks are low to none. However, talking about a DKA episode may bring up difficult memories for some patients or carers. Information to seek support from a relevant patient support group (e.g., Diabetes UK) will be provided if needed. Participants won't directly benefit, but the study will help improve future DKA care. Where is the study run from? University of Birmingham. The wider DEKODE project involves hospitals across the UK. When is the study starting and how long is it expected to run for? June 2025 to August 2028 Who is funding the study? NIHR Academy, via an NIHR Advanced Fellowship awarded to Dr Punith Kempegowda Who is the main contact? Dr Punith Kempegowda, p.kempegowda@bham.ac.uk Work Package 1 – Assessing inequities in DKA care and outcomes in the UK Objective 1.1: Crude incidence rate of DKA (number of new cases per 100,000 person-years), measured using CPRD Aurum/GOLD linked to HES (ICD-10 codes E10.0–E14.1), calculated annually from 01/01/2001 to 31/12/2023, stratified by age, sex, ethnicity, deprivation, mental health status, and region. Objective 1.2: Length of hospitalisation, measured using HES data, at the index DKA admission. Work Package 2 – Lived experiences of people treated for and treating DKA Patient-reported experience of DKA care, measured using the NHS Inpatient Questionnaire for people with diabetes (Microsoft Forms) and the EQ-5D-Y questionnaire, at baseline (inpatient admission), 3 months and 6 months post-discharge. Work Package 3 – DEKODE model implementation and effectiveness Variation in DEKODE implementation across NHS Trusts, measured using thematic analysis of semi-structured interviews with stakeholders (applying NASSS and CFIR frameworks), at the time of interview across six consecutive quarterly DEKODE data cycles. Work Package 4 – Investigating recurrent DKA Frequency and predictors of recurrent DKA (defined as ≥2 DKA episodes), measured using pseudonymised DEKODE national audit data and NHS hospital records, across the full study period. Work Package 5 – Health economics evaluation of the DEKODE model Cost of managing a single DKA episode, measured using NHS procurement data and DEKODE audit data (direct and indirect costs), at baseline and at 12, 18, and 24 months after DEKODE adoption in participating institutions. There are no secondary outcomes Ethics approval required HRA and Health and Care Research Wales (HCRW)

Health Research Authority, 2 Redman Place, Stratford

London United Kingdom E20 1JQ 25/IEC08/0011 10.1186/ISRCTN17096714 344284 CPMS: 56443, NIHR: 303671 344284 56443 303671 Multi-component, mixed-methods study programme Observational Cohort study Treatment 2028-08-30T00:00:00.000Z United Kingdom England University of Birmingham

Department of Applied Health Sciences Murray Learning Centre

Birmingham England B15 2TT University Hospitals Birmingham NHS Foundation Trust

Queen Elizabeth Hospital Mindelsohn Way Edgbaston

Birmingham England B15 2GW RRK@2.16.840.1.113883.2.1.3.2.4.18.48 false Work Package 1: Patients admitted with DKA from 1 January 2001 to 31 December 2023. Work Package 2: 1. Patients: 1.1. Those admitted to the hospital with DKA 1.2. Have the capacity to provide consent 1.3. Aged 16-99 years 2. Carers: 2.1. Those who are identified by patients as recruited above 2.2. Have the capacity to provide consent 2.3. Aged 16-99 years 3. Healthcare workers: 3.1. Those involved in treating DKA for patients recruited above 3.2. Have the capacity to provide consent Work Package 3: Healthcare professionals involved in providing DKA care in hospitals participating in DEKODE Mixed 16 Years 99 Years All 90 0 Work Package 1: Individuals with non-diabetic ketoacidosis or other metabolic disorders that could confound the study results Work Package 2: 1. Patients without DKA 2. Providers not directly involved in DKA care 3. Unable to provide consent Work Package 3: Individuals who do not have sufficient interaction with the DKA care process 2025-06-23T00:00:00.000Z 2027-08-31T00:00:00.000Z Diabetes mellitus Nutritional, Metabolic, Endocrine The DEKODE study is designed to improve the care of people admitted to hospital with diabetes-related emergencies. It consists of four work packages, each focusing on a specific aspect of DKA care. Below is a summary of what will happen to participants in each work package, presented in a clear and straightforward way. Work Package 1: Understanding Inequalities in DKA Care We will use anonymised health records of patients with DKA from 2001 to 2023 to study differences in care and outcomes across regions, age groups, ethnicities, and other factors. This part of the study does not involve direct interaction with participants. Work Package 2: Exploring Lived Experiences of Patients, Carers, and Healthcare Professionals Patients: Patients treated for DKA will be invited to complete a short online questionnaire about their hospital experience. Some patients will be invited for a one-on-one online interview lasting about 30 minutes, where they can share their experiences before, during, and after their hospital stay. A follow-up questionnaire will be sent to patients 3 and 6 months after their discharge to understand any changes in their health and recovery. Carers: Carers (e.g., family members or friends) identified by the patients with their consent will also be invited to participate. They will be interviewed separately to share their perspective on supporting someone with DKA. Healthcare professionals: Healthcare professionals involved in DKA care (e.g., doctors, nurses, and specialist teams) will be invited to take part in online interviews or focus groups. These will last about 30–60 minutes and explore their experiences in managing DKA. All interviews and focus groups will take place online (e.g., via Zoom) and will be audio-recorded. Work Package 3: Evaluating the Implementation of the DEKODE Model Researchers will study how hospitals across the UK have adopted the DEKODE model for standardising DKA care. Healthcare professionals from hospitals using the DEKODE system will be invited for interviews or focus groups to discuss the following: 1. How the model is being used in their hospital. 2. Any challenges or successes in implementing the system. Around 20–30 professionals will participate in this part of the study. Work Package 4: Investigating Recurrent DKA: A Retrospective Cohort Analysis Using DEKODE This retrospective cohort study will analyse individuals with ≥2 DKA episodes using DEKODE data and hospital records to identify key clinical determinants, risk factors, and healthcare utilisation patterns associated with recurrent DKA. Statistical analyses, including logistic regression and Kaplan-Meier survival analysis, will assess independent predictors of recurrence, clinical outcomes, and the impact of DEKODE implementation on reducing recurrence rates Work Package 5: Health Economics Evaluation Researchers will analyse the financial impact of using the DEKODE model in hospitals by comparing the cost of DKA care before and after its implementation. This part will rely on anonymised hospital data and does not involve any interaction with participants. Other The datasets generated during and/or analysed during the current study will be available upon request from Punith Kempegowda (p.kempegowda@bham.ac.uk). Type of data: Qualitative When the data will become available and for how long: 2029, 4 years By what access criteria data will be shared, including with whom: requests will be reviewed case-by-case, and data will be shared upon reasonable request For what types of analyses: secondary qualitative analysis What mechanism? Researchers wishing to access the pseudonymised dataset must submit a written request to the Chief Investigator (Dr Punith Kempegowda, p.kempegowda@bham.ac.uk), outlining the proposed analysis. These will then be reviewed on a case-by-case basis and access will require a signed data-sharing agreement with the University of Birmingham. Whether consent from participants was obtained: Yes Comments on data anonymisation: Only anonymised data will be provided Any ethical or legal restrictions: the requesting researcher should have appropriate ethical and legal approval to request data for further analysis. Available on request 2026 Protocol article in https://pubmed.ncbi.nlm.nih.gov/42780780/ (added 25/09/2026) Protocol

8feb4b65-f215-4641-8996-105f06af3cf8 ba74f382-4dab-4281-80d3-19ab3d1c6b9a 3f8e855a-f000-491f-9478-7414f2d944dc 355e8323-3f92-4392-b987-ef681fa9fca6 Yes Protocol file 49713_PROTOCOL.pdf 1143fb90-d300-4b9a-a71c-58aab1f1f4c0 true application/pdf 753154 dd85f35cabcc811841bb4b8f1191aa5b Punith Kempegowda https://orcid.org/0000-0003-0954-6512 Principal investigator

Department of Applied Health Sciences, University of Birmingham

Birmingham United Kingdom B15 2TT +44 (0)7721 930777 p.kempegowda@bham.ac.uk Public Kalyaani Persad https://orcid.org/0009-0009-1816-2909 Scientific Public

Department of Applied Health Sciences, University of Birmingham

Birmingham United Kingdom B15 2TT +44 (0)7584811046 k.persad@bham.ac.uk Public University of Birmingham Hospital/treatment centre https://ror.org/03angcq70 Non-commercial National Institute for Health and Care Research http://dx.doi.org/10.13039/501100000272 61644978 true Care-experienced yOung peopLe’s mentaL heAlth help-seekinG bEhaviours (COLLAGE): A mixed-methods observational study using a cross-sectional survey and follow-up qualitative interviews to investigate mental health help-seeking among care-experienced young people in England COLLAGE Care-experienced young people in England experience high levels of mental health need, yet many do not access appropriate support. There is limited evidence on how they seek help, the barriers and facilitators they encounter, and how these differ for those with intersecting marginalised identities. The aim of this study is to investigate mental health help-seeking among young people aged 13–25 with experience of out-of-home care in England. The specific objectives are: 1. To examine patterns of help-seeking behaviour, including formal and informal sources of support 2. To identify barriers and facilitators to accessing support 3. To explore how intersecting marginalised identities (e.g. sexual orientation, gender identity, ethnicity, neurodivergence, disability) shape help-seeking experiences 4. To explore in-depth experiences of help-seeking among under-represented groups through qualitative interviews 5. To generate an overall understanding of mental health help-seeking by drawing on findings from the different study components to inform recommendations for improving mental health and social care services. Background and study aims Care-experienced young people in England often have high levels of mental health needs, but many do not receive the support they need. There is limited research on how they try to get help, what barriers they face, and what kinds of support work best, especially for those with multiple marginalised identities (for example, being LGBTQ+, from ethnically minoritised backgrounds, neurodivergent, or living with disabilities). The aim of this study is to understand how young people aged 13 to 25 with experience of out-of-home care seek help for mental health problems, and how services can be improved to better meet their needs. Who can participate? Young people in England who have experience of out-of-home care, including foster care, residential care, or kinship care (living with friends or relatives). For the survey: young people aged 13 to 25 years For interviews: young people aged 16 to 25 years Participants must have been in care within the past 10 years for at least 3 months. Young people currently receiving urgent or crisis mental health care will not be able to take part. What does the study involve? The study includes three parts. First, a review of existing research will be carried out to understand what is already known about help-seeking in care-experienced young people. Second, an online survey (about 150 participants) will ask about mental health, how participants seek help, and any difficulties they experience when trying to access support. Third, online interviews (about 20 to 30 participants) will explore these experiences in more detail, particularly for young people from under-represented groups. Some interviews may be supported by trained peer researchers with lived experience of care. Findings from each part of the study will contribute to an overall understanding of help-seeking and how support can be improved. What are the possible benefits and risks of participating? There are no direct benefits to participants, but the study will help improve mental health and social care services for care-experienced young people in the future. Some participants may feel upset when thinking about difficult experiences. To reduce this risk, the study is designed to be sensitive and supportive. Participants can skip questions, take breaks, or stop at any time. Information about support services will be provided, and interviewers are trained to respond appropriately to distress. Participants may receive a small voucher as a thank you for taking part. Where is the study run from? University of Birmingham (UK) When is the study starting and how long is it expected to run for? January 2026 to November 2026 Who is funding the study? The study is funded by the National Institute for Health and Care Research (NIHR) Research Programme for Social Care (RPSC) (UK) Who is the main contact? Dr Willem Stander, w.stander@bham.ac.uk Help-seeking behaviour the Actual Help-Seeking Questionnaire (AHSQ) survey completion (single timepoint) Help-seeking intentions the General Help-Seeking Questionnaire (GHSQ) survey completion (single timepoint) Help-seeking barriers the Barriers to Adolescents Seeking Help Scale – Brief Version (BASH-B) survey completion (single timepoint) Depression symptoms the Patient Health Questionnaire-2 (PHQ-2) survey completion (single timepoint) Anxiety symptoms the Generalized Anxiety Disorder-2 (GAD-2) survey completion (single timepoint) Self-harm items from the CDC Youth Risk Behavior Survey (YRBSS) survey completion (single timepoint) Suicidality items from the CDC Youth Risk Behavior Survey (YRBSS) survey completion (single timepoint) Associations between help-seeking behaviours and demographic and care-related characteristics self-reported survey data analysed using regression models survey completion (single timepoint) Experiences of mental health help-seeking semi-structured qualitative interviews analysed using reflexive thematic analysis the time of interview Preferences for mental health support and services semi-structured qualitative interviews analysed using reflexive thematic analysis the time of interview Ethics approval required University of Birmingham Humanities and Social Sciences Research Ethics Committee

Research Governance Team, The University of Birmingham, Edgbaston

Birmingham United Kingdom B15 2TT ERN_4998 10.1186/ISRCTN61644978 NIHR: 207636, CRD420251047424 207636 CRD420251047424 Observational Cross sectional study 2026-11-30T00:00:00.000Z United Kingdom England Participants are recruited online across England; no physical recruitment sites are used

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- England - false 1. Aged 13 to 25 years (survey); 16 to 25 years (interviews) 2. Experience of out-of-home care in England (including foster care, residential care, or kinship care) 3. Out-of-home care experience within the past 10 years and lasting at least 3 months 4. Able to provide informed consent (or assent where appropriate) Mixed 13 Years 25 Years All 175 0 1. No experience of out-of-home care in England 2. Out-of-home care experience less than 3 months or more than 10 years ago 3. Currently receiving mental health crisis care or emergency mental health support (e.g., inpatient psychiatric care or intensive crisis services) 2026-01-05T00:00:00.000Z 2026-08-31T00:00:00.000Z Mental health help-seeking in young people with experience of out-of-home care in England Mental and Behavioural Disorders This is a mixed-methods observational study including an evidence synthesis, a cross-sectional online survey, and follow-up qualitative interviews. First, a systematic review of international literature will be conducted to identify existing evidence on mental health help-seeking among care-experienced young people. Second, a cross-sectional online survey will be administered to approximately 150 young people aged 13–25 years in England with experience of out-of-home care. The survey will be hosted on Qualtrics and will collect data on help-seeking behaviours, barriers and facilitators to accessing support, mental health indicators (including anxiety, depression, self-harm and suicidality), and demographic and care-related characteristics. Data will be analysed using descriptive statistics and regression modelling to examine patterns and associations. Third, semi-structured online interviews will be conducted with a purposive sample of approximately 20–30 young people aged 16–25 years, with a focus on those with intersecting marginalised identities. Interviews will explore experiences of mental health help-seeking, barriers and facilitators, and preferences for support. Interviews will be audio-recorded, transcribed, anonymised, and analysed using reflexive thematic analysis. Findings from each study component will contribute to an overall understanding of mental health help-seeking among care-experienced young people. The study is co-produced with a Young Advisors Group of care-experienced young people, who contribute to study design, data collection, and interpretation. Behavioural Not expected to be made available 49374a3d-0626-4d9a-966a-01c4b2902d6b 7017d068-da8c-4510-ad0d-5cd14362478e 9368d61a-e3f1-4ada-bd89-a9f64ced2f7d No Willem Stander https://orcid.org/0000-0002-3664-4647 Principal investigator Scientific Public

University of Birmingham, Edgbaston

Birmingham United Kingdom B15 2TT +44 (0)1214143114 w.stander@bham.ac.uk Public University of Birmingham https://ror.org/03angcq70 Non-commercial National Institute for Health and Care Research http://dx.doi.org/10.13039/501100000272 17520398 true Feasibility and acceptability of a home-based arm-crank exercise programme for people living with spinal cord injury Arm-Crank SCI 1. Is a 12-week online home-based ACE programme, delivered three times a week, acceptable for people with SCI? 2. Is the ACE programme safe to be undertaken by people with SCI at home? 3. Is the ACE programme feasible, with potential to be integrated in the NHS SCI care pathways? Background and study aims This research is about testing a home-based exercise programme designed to help people with spinal cord injury (SCI) stay healthy and reduce the risk of future health problems. The programme uses Arm-Crank Exercise (ACE), where participants sit and use their arms to turn the handles of a stationary arm bike, similar to leg cycling but using your arms. Each session follows a routine and aims to improve fitness, mobility, and general wellbeing in people with SCI. This research will test whether an online ACE programme is practical to deliver, acceptable to participants, and potentially suitable for use in the NHS. The research is carried out in people’s homes. Who can participate? We will invite 50 people with long-term SCI who cannot walk unaided to take part. Participants will be recruited through NHS spinal clinics and charities. What does the study involve? The 12-week programme will include three group sessions per week, delivered live via Zoom. Participants can also use recorded sessions if they prefer more flexibility. We will monitor how many people take part, how many complete the programme, and how often they join sessions. Participants will track their effort using a heart rate monitor and report any fatigue or shoulder pain every two weeks. Any issues or side effects will be recorded. At the end of the programme, participants will be invited to complete a short survey and join a group discussion about their experience and how the programme could be improved. Their feedback will help us plan a larger study in the future. What are the possible benefits and risks of participating? After the programme, we expect that participants may improve fitness, physical function, such as strength of the upper body, seated balance, and mental health. Where is the study run from? University of Birmingham (UK) When is the study starting and how long is it expected to run for? August 2026 to April 2028 Who is funding the study? National Institute for Health and Care Research (NIHR) (UK). Who is the main contact? arm-crank-study@contacts.bham.ac.uk Read the study information sheet and express your interest in participation here: https://itm-redcap.bham.ac.uk/surveys/?s=KTRMACLT7KAPF9EM Participation rate recruitment logs documenting number of participants recruited per month from NHS sites and community sources, supplemented where feasible by logs of individuals declining participation and qualitative feedback from focus groups continuously during the recruitment period Adherence to the intervention number of completed sessions versus prescribed sessions recorded via class attendance logs and participant exercise diary, expressed as a percentage of total sessions offered throughout the 12 week intervention period Safety, including fatigue, shoulder pain, and adverse events Fatigue Severity Scale, Wheelchair User’s Shoulder Pain Index, and self reported adverse events collected via participant report during biweekly telephone calls baseline, every 2 weeks during the 12 week intervention, and end of intervention at 12 weeks Attrition study withdrawal records and completeness of follow up data from study database assessed at end of intervention at 12 weeks and at any point of withdrawal during the study Usability, perceived effectiveness and satisfaction a self-reported online EXIT survey 12 weeks Functional capacity and cardiovascular fitness Six-Minute Arm-Crank test (6-MAT) with recording of rating of perceived exertion RPE, heart rate HR and distance via arm ergometer and remote supervision baseline, 12 weeks Health-related quality of life across physical and mental health domains Short Form 36 walk-wheel questionnaire (a modified version for SCI) baseline, 12 weeks Health-related quality of life and health utilities EQ-5D-5L and SF-6D questionnaires with comparative analysis alongside SF-36 walk-wheel outputs baseline, 12 weeks Health care resource use ModRUM questionnaire for self-reported resource use and Case Report Form for extraction of resource use data from NHS records baseline, 12 weeks Waist circumference self-measured waist circumference in the supine position using a measuring tape by a carer or family member under remote supervision baseline, 12 weeks Bowel function International Spinal Cord Injury Bowel Function Basic Data Set questionnaire baseline, 12 weeks Leisure time physical activity level leisure time physical activity questionnaire baseline, 12 weeks Ethics approval required West of Scotland REC 5

Suite 203, The Pentagon Centre36 Washington Street

Glasgow United Kingdom G3 8AZ 26/WS/0045 10.1186/ISRCTN17520398 360942 CPMS: 69526, NIHR: 209820 360942 69526 209820 Interventional Non-randomized controlled trial Open (masking not used) Uncontrolled Single Treatment Not applicable Treatment 2028-04-30T00:00:00.000Z United Kingdom England University of Birmingham

School of Sport, Exercise and Rehabilitation Sciences Edgbaston

Birmingham England B15 2TT Sheffield Teaching Hospitals NHS Foundation Trust

Northern General Hospital Herries Road

Sheffield England S5 7AU RHQ@2.16.840.1.113883.2.1.3.2.4.18.48 Stoke Mandeville Hospital

Mandeville Road

Aylesbury England HP21 8AL RXQ02@2.16.840.1.113883.2.1.3.2.4.18.48 false 1. Aged 16 years and older 2. Diagnosed with cervical, thoracic, or lumbar SCI, and medically stable 3. Can provide informed consent and understand and follow instructions for assessment and intervention 4. Use a wheelchair for >=75% of their waking hours 5. Have sufficient elbow flexors strength to operate an arm-crank ergometer 6. Have access to a device and internet connection capable of running Zoom Due to the scope of this study being a feasibility study, the instructions will be given in English. We are aware of the translation services available in the NHS and will consider this for a future trial for the study to be fully inclusive. Additionally, the inclusion criteria for recruiting stakeholders to the qualitative focus group study are: 1. Aged 18 years and above 2. Qualified specialists for caring patients with spinal cord injury in the NHS SCI care pathways 3. At least 6 months experience in caring for people with SCI Mixed 16 Years 120 Years All 60 0 1. Presence of unstable or acute medical conditions that are contraindications for exercise 2. Clinical advice against unsupervised exercise from a consultant or physiotherapist 3. Participation in another research study targeting rehabilitation or health management 2026-08-12T00:00:00.000Z 2027-07-31T00:00:00.000Z Spinal cord injury Nervous System Diseases This is a prospective, non-randomised, single-arm feasibility study, informed by prior research, PPIE input, and the multidisciplinary expertise of the study team. The study will evaluate the feasibility of delivering the intervention and levels of participant engagement in 50 individuals with SCI. We will also conduct qualitative interviews and focus groups with participants, individuals excluded due to language or digital barriers, and healthcare professionals to explore the intervention’s acceptability, safety, and practical considerations for future NHS implementation Work package 1. Feasibility study Planned intervention: Home-based ACE programme The proposed intervention is a structured 12-week ACE programme delivered remotely in the participant’s home. After reviewing best practice guidelines highlighted in relevant literature and discussing with our PPIE groups what would be an appropriate commitment for the programme, the intervention volume was set to 30 minutes per day, 3 days per week, for 12 weeks. The programme duration was determined to be in line with a typical community-based exercise programme for health in individuals with SCI. This dose and duration of the intervention allows time for participants to engage in an evidence-based intervention, progress, and see improvement Equipment provision and induction session To support safe and effective participation, all participants will be provided with: 1. A portable arm ergometer (MagneTrainer ER) and an anti-slip mat 2. A chest-worn heart rate HR monitor (Polar H10), a widely used device for monitoring HR in SCI exercise interventions 3. Gripping aids, if needed Each participant will receive a personalised induction session of approximately 45 minutes delivered via Zoom, or in person either in clinic or via a home visit, depending on individual needs and preferences. This session will cover: 1. Introduction to the aims and expectations of the programme 2. Safe setup and positioning of the arm ergometer 3. Instructions for joining Zoom sessions, camera and sound setup, and using the HR monitor with the Polar Beat app. The research team will help participants set up the Polar Beat app if needed. A project-dedicated account will be created for each participant so that there is no identifiable data going to the app developer 4. A supervised one-to-one ACE trial of approximately 20 minutes to confirm correct technique and screen for any safety concerns 5. Agreement of a personalised weekly schedule, considering the participant’s availability and needs Exercise class format and delivery The research fellow appointed in this study will have the relevant qualification, for example a bachelor’s degree in physiotherapy or sports, exercise and health sciences, and be trained to deliver the intervention safely and effectively Participants will join three live group sessions per week via Zoom for 12 weeks. Each class will follow a standardised structure: 1. 5 minutes pre-session setup and check-in 2. 5 minutes warm-up 3. 30 minutes main ACE session using an interval training format, alternating moderate to vigorous intensity arm cycling with recovery periods. Research suggests that interval training elicits higher enjoyment versus moderate exercise in individuals with SCI 4. 5 minutes cool-down and stretches Live classes will be scheduled at set times, with sessions opening 15 minutes before and remaining open 15 minutes after for optional peer interaction and support. Breakout rooms will be used for people who prefer socialising in a smaller group. This structure is informed by evidence that social support enhances exercise adherence Participants who are unable to attend a live session will have the option to access the pre-recorded session. Attendance will be tracked through a study-provided exercise diary To ensure effective monitoring, group sizes will be limited so that the trainer can observe all participants on screen and offer real-time guidance. Participants will be advised to have a family member, carer, or companion present or nearby during the sessions for added safety Monitoring intensity, safety and adherence Exercise intensity will be monitored as per recommendations for delivering and evaluating exercise interventions involving people with SCI using: 1. Heart rate, recorded via Polar H10 and synced to the Polar Beat app 2. Participant-rated perceived exertion RPE logged at each session Participants will be trained during induction to record and share HR data. RPE will be logged in an exercise diary. Data from HR monitors and RPE scores will be documented by participants in the exercise diary Safety monitoring will include: 1. Biweekly REDCap online surveys of approximately 10 minutes assessing fatigue using the Fatigue Severity Scale and shoulder pain using the Wheelchair User’s Shoulder Pain Index 2. Self-reported logs of adverse events 3. Telephone check-ins by the research team every two weeks to identify any safety concerns or non-engagement Work package 2. Qualitative interviews and focus groups 1. Focus groups with study participants. Four online focus groups of approximately 60 minutes each with a total of 20 participants, five per group, who have completed the programme will be conducted. Participants will be purposively sampled to review adherence and access and inclusivity. Where possible, appropriate representation across sex, ethnicity and socio-economic status will be ensured 2. Focus groups with healthcare professionals. Two online focus groups with a total of 10 healthcare professionals representative of SCI care pathways in England will be conducted via videoconferencing. Healthcare professionals working in spinal units where study participants are outpatients will be invited. Clinicians and physiotherapists involved in this study will also be invited to take part 3. Focus group schedule. Focus groups will provide in-depth insights into participants’ views on the feasibility, acceptability and safety of the intervention. Discussions will explore perceived effectiveness, strengths and challenges related to implementation, and any adaptations needed to support engagement, delivery and overall impact Behavioural The datasets generated during and/or analysed during the current study are/will be available upon request from (Dr Chloe Chiou, s.chiou@bham.ac.uk, anonymous data may be shared with other research groups for research use only after the full results are published. The data will be available for 10 years. Data are available upon reasonable requests directly to Dr Chiou. Available on request

Flyer

2ecab95d-f256-4c52-a1c7-ca688a7162bf fe298465-3058-480d-81fa-5b8151841dfe 6437da27-3086-41ac-adce-7cb6c47d9985 ad2477fc-804e-4552-a773-c17dcb465826 Yes Flyer 49704 New Arm-Crank SCI study flyer 2_v1 with QR code.pdf f3f12bfa-3165-48a7-a793-eaeb5e5e3ac8 true application/pdf 2763119 bd4e72c54c98bc95b47db9ded4258a8a Chloe Chiou https://orcid.org/0000-0002-4200-5243 Principal investigator Scientific Public

School of School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Edgbaston

Birmingham United Kingdom B15 2TT +44(0)121 414 5315 arm-crank-study@contacts.bham.ac.uk Public Yu-Hsien Lee https://orcid.org/0009-0006-9734-314X Scientific Public

School of Sport, Exercise and Rehabilitation Sciences The University of Birmingham, Y14 Edgbaston

Birmingham United Kingdom B15 2TT - y.lee.4@bham.ac.uk Public University of Birmingham University/education https://ror.org/03angcq70 Non-commercial National Institute for Health and Care Research http://dx.doi.org/10.13039/501100000272 66242439 true Harvesting STEM cells through intra-apheresis EXercise STEM-Ex The primary aim of this project is to examine the clinical effectiveness of undertaking intermittent periods of cycling (intra-apheresis cycling) during peripheral blood stem cell donations vs. standard of care in people with myeloma and volunteer, matched donors. Background and study aims Every year, more than 90,000 people around the world receive stem cell transplants to treat illnesses such as myeloma, a type of blood cancer. Stem cells need to be collected from the donor’s blood prior to transplant, and this process takes at least three hours and sometimes has to be repeated over several hospital visits to collect enough cells. As well as the time burden, low cell numbers and complications after transplant still happen, highlighting a clinical need to develop novel approaches. In earlier work, the research team found that attaching pedals to the end of a chair and performing light cycling spaced out over 3 hours increased the number of stem cells and white blood cells important for a successful transplant. The team now aim to find out whether people with myeloma and volunteer matched donors can comfortably undertake brief periods of light cycling during their donation, and whether this helps collect more cells and increase the success of the transplant. The findings will help plan for the future use of this concept in a hospital setting to improve stem cell collections for people with myeloma, volunteer donors and other conditions. Who can participate? Patients with myeloma who have a scheduled blood stem cell collection and volunteer matched donors who have a scheduled blood stem cell collection. What does the study involve? After consent and screening, donors will be randomly placed into either their standard stem cell donation group or a cycling group (plus standard donation). Those in the cycling group will pedal lightly for 4 minutes every 20 minutes during their stem cell donation. Blood samples will be taken from both groups before and afterwards, but this will be separate and not affect the stem cells collected for transplant. What are the possible benefits and risks of participating? Benefits: The research team can provide you with a report of your activity levels measured during the study. By taking part, you will help them to evaluate the impact of a novel non-drug-based protocol aiming to directly improve clinical care for people with myeloma and other illnesses. Once the study has finished, participants will be provided with information on the findings and plans for future projects. Risks: Peripheral Blood Stem Cell Collection Participants will be informed by their medical team of the risks associated with undergoing a peripheral blood stem cell collection. Blood Samples For the research blood samples, the team will need to briefly insert a small needle into a vein in the participant's arm twice during the stem cell collection session (before and after). As far as discomfort is concerned, there might be a small sting with insertion, but otherwise, these procedures are not usually painful. There is a very small risk of infection and bruising at the site of insertion. This risk will be much reduced using trained medical staff and good procedures. The amount of blood taken each time (40mL) is equivalent to less than 3 teaspoons. It is safe to lose this amount of blood during the stem cell collection session, and most importantly, it will not impact the quantity/quality of blood cells being reinfused into the body. Fatigue During Exercise The exercise performed is light, and so the chances of any risks are extremely low. Participants may feel a bit tired while they’re cycling, but this is normal and will be short-lived. They should fully recover within hours of the process. There is a very small risk of unexpected heart problems during any type of exercise, but this is an extremely low risk. Although specific figures are not available for people with myeloma, the risk of a serious heart problem in adults without heart disease only happens once every 400,000 – 800,000 hours of vigorous exercise. Even in patients with heart conditions, who are recognised as high risk, the likelihood is still extremely small (1 death every 176,000 hours of vigorous exercise). Participants can stop exercising at any time if they start to feel uncomfortable. Where is the study run from? The Centre for Clinical Haematology (Birmingham Centre for Cellular Therapy and Transplant) at the Queen Elizabeth Hospital, Birmingham, UK. When is the study starting and how long is it expected to run for? June 2026 to March 2027. Who is funding the study? The Academy of Medical Sciences, UK. Who is the main contact? Phoebe Cox, stemex@contacts.bham.ac.uk Rate of stem cell collection flow cytometry to quantify CD34+ cells collected per minute the end of stem cell collection Final CD34+ dose flow cytometry to quantify CD34+ cells per kg of body mass the end of stem cell collection Time to achieve the target dose flow cytometry to quantify CD34+ cells per hour and day the end of stem cell collection Engraftment outcomes flow cytometry to quantify neutrophil, lymphocyte and platelet recovery a time point following stem cell transplant Feasibility outcomes study data recording recruitment, adherence and attrition rate the end of stem cell collection Acceptability outcomes symptom questionnaires: for autologous donors, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the EORTC myeloma-specific module (EORTC QLQ-MY20); and, for allogenic donors, the Short Form-12 (SF-12) quality of life questionnaire, and an interview, a time point during and following the stem cell collection Physiological outcomes, including the rating of perceived exertion, continuous heart rate monitoring, pedal cadence, and cycling interval average power output the Borg scale, a wristwatch (beats per minute and % of age-predicted heart rate maximum), and pedals during the stem cell collection Immunological outcomes flow cytomtery to quantify concentrations of immune cell subsets pre and post stem cell collection Ethics approval required Health and Social Care Research Ethics Committee A (HSC REC A)

Office for Research Ethics Committees Northern Ireland (ORECNI) Business Services Organisation Unit 4, Lissue Industrial Estate West

Lisburn United Kingdom BT28 2RF 26-NI-0009 10.1186/ISRCTN66242439 326850 CPMS: 70257, SBF0010\1201 326850 70257 SBF0010\1201 Interventional Randomized controlled trial Open (masking not used) Active Parallel Supportive care Not applicable Treatment 2027-06-30T00:00:00.000Z United Kingdom Queen Elizabeth Hospital

Mindelsohn Way Edgbaston

Birmingham England B15 2GW RTHH6@2.16.840.1.113883.2.1.3.2.4.18.48 false 1. Inclusion Criteria for Patient Donors The donor can be included if they have/ are: 1.1. A clinical diagnosis of Myeloma 1.2. A scheduled autologous stem cell collection 1.3. > 18 years old 1.4. The capacity to consent to taking part in the study 1.5. A consultant determined score of ‘0’ or ‘1’ on the ECOG Performance Status Scale 1.6. Consultant and donor agree that donor is capable of lightly pedalling for a maximum of 12 minutes per hour during the stem cell collection 2. Inclusion Criteria for Volunteer Donors The donor can be included if they have/ are: 2.1. > 18 years old 2.2. A scheduled allogeneic stem cell collection 2.3. The capacity to consent to taking part in the study 2.4. Are able to lightly pedal for a maximum of 12 minutes per hour of their stem cell collection, and their consultant agrees 3. Inclusion Criteria for Survey 3.1. > 18 years old 3.2. Have the capacity to consent to taking part in the study 3.3. All people with a clinical diagnosis of myeloma will be included 3.4. All people who have previously undertaken a peripheral blood stem cell collection will be included (patients with myeloma and allogeneic (volunteer matched) donors) 3.5. All healthcare professionals who have previously worked with donors receiving a peripheral blood stem cell collections will be included 3.6. Family members of close friends of people who have previously undertaken a peripheral blood stem cell collections will be included 4. Eligibility Criteria for Interviews (Donors) A CYCLE participant in the STEM-Ex study 5. Eligibility Criteria for Interviews (Healthcare Professionals) 5.1. Directly involved in stem cell collections 5.2. Involved in the STEM-Ex study Mixed 18 Years 110 Years All 70 0 1. Exclusion Criteria for Patient Donors The donor will be excluded if they have/ are: 1.1. Uncontrolled blood pressure 1.2. Previously had a stem cell transplant 1.3. Joint problems that might limit ability to cycle e.g., bony deposits, osteoarthritis, collapsed spine, spine compression and/or an unstable spine 1.4. An abnormal electrocardiogram (ECG), which measures heart rhythm 1.5. Additional health conditions that might put them at risk during this study e.g. brain and/or lung conditions 1.6. Pregnant or planning a pregnancy 2. Exclusion Criteria for Volunteer Donors The donor will be excluded if they have/ are: 2.1. Uncontrolled blood pressure 2.2. Joint problems that might limit your ability to cycle e.g., osteoarthritis 2.3. An abnormal ECG measurement 2.4. Additional health conditions that might put them at risk for this study e.g. heart complications, brain and/or lung conditions 2.5. Pregnant or planning a pregnancy 3. Eligibility Criteria for Survey Not fulfilling one of the three inclusion criteria 4. Eligibility Criteria for Interviews (Donors and Healthcare Professionals) Not fulfilling one of the inclusion criteria 2026-06-29T00:00:00.000Z 2027-03-31T00:00:00.000Z Multiple myeloma Cancer Hypothesis This project will be conducted as a pilot trial to address key uncertainties in designing a definitive randomised controlled trial, which will test the hypothesis that cycling during a stem cell collection elicits a higher stem cell dose and speeds up collection time, compared to standard of care (control). Study Sample Size Approximately 200 autologous donations for myeloma will take place at the Birmingham Centre for Cellular Therapy and Transplant over the planned 15-month data collection period. In line with our patient engagement, a recruitment rate of 25% is sufficient to fulfil the feasibility objectives of this study. Anticipating a 50% recruitment rate for allogeneic donors, the study will recruit 20 healthy donors for equal randomisation, using the web-based platform called Sealed Envelope, into the cycling or control groups. Study Design and Methodology The design and methodology outlined below are the same for both myeloma (patients) and healthy donors: 1. Before Study (30-minute time commitment) As part of the participants' routine clinical appointments, as they prepare for the stem cell collection, the procedures outlined below will be conducted: 1.1. Eligibility An assessment of eligibility for the study involves asking some routine questions. 1.2. Informed Consent A copy of the study information leaflet will be provided, and the participant will be given the opportunity to discuss details with the medical team. The participant can take as long as they wish to consider taking part in the study. If the participant is happy to take part and is eligible, they will be asked to sign a consent form. A letter will be sent to the participants' GP to confirm study participation. 1.3. Questionnaires Questionnaires relating to quality of life (i.e., physical and mental health) and physical capacity to undertake the study. 1.4. Activity Level Assessment A wrist watch will be given to each participant to measure objective physical activity for a 3-day period. The participant doesn't need to do anything during this period. 2. Day of Stem Cell Collection (Both Groups: 45-minute time commitment) All participants will be attending the Birmingham Centre for Cellular Therapy and Transplant for their scheduled stem cell collection. It is important to note that all planned medical care will remain identical and medical procedures will not be altered based on group allocation (notably myeloma cohort). In addition to the donor's standard medical care, the below procedures will take place: 2.1. General Health Assessment The medical team will measure participants' height, weight, waist circumference, resting heart rate, blood pressure and pulse. These procedures will run in parallel with the appointment with the consultant. 2.2. Electrocardiogram (ECG) This is a simple test that checks heart rhythm and electrical activity. Sensors are attached to the skin to detect electrical signals produced by the heart when it beats. 2.3. Group Allocation Random allocation to either the cycling or the control group. 3. Cycling Group - Stem Cell Collection (3-4 hour time commitment) In the cycling group, participants will continue with the stem cell collection as normal. In addition, pedals will be provided in front of the chair, and they will be asked to pedal lightly for 4 minutes every 20 minutes. This typically lasts for approximately 3-4 hours; however, there will be 16 minutes of complete rest in between each interval. The settings on the bike can be altered at any time to ensure that the cycling is perceived as '12' on the validated 'rating of perceived exertion' scale, ranging from '6-20' - this is deemed to be 'light intensity'. Participants will be under constant supervision by the members of the research and medical team during this time. During the procedure, the following measures will be taken: - Perceived exertion/ability to cope with cycling will be measured using the chart above prior to starting and periodically during the trials. - Heart rate will be measured by using a wristwatch. - Blood pressure will be monitored via an automated stress-testing blood pressure monitor using a cuff placed around the upper arm. - Pedal speed. - Cycling Power Output. - Questionnaires relating to the level of comfort and symptoms experienced during and after the procedure (pain, tiredness, nausea, anxiety, drowsiness, appetite, well-being and shortness of breath) - Overall satisfaction and feedback on the session. - Blood Sampling - before and after the procedure, a small peripheral blood sample (20mL) will be collected into EDTA-coated vacutainers. 4. Control Group (3-4 hour time commitment) In the control group, participants will continue with their stem cell collection as normal. Participants will be asked to complete questionnaires relating to their level of comfort and symptoms experienced during and after the procedure, as well as overall satisfaction and feedback on the session. During the procedure, the following measures will be taken: - Heart rate will be measured by using a wristwatch. - Blood pressure will be monitored via an automated stress-testing blood pressure monitor using a cuff placed around their upper arm. - Questionnaires relating to the level of comfort and symptoms experienced during and after the procedure (pain, tiredness, nausea, anxiety, drowsiness, appetite, well-being and shortness of breath) - Overall satisfaction and feedback on the session. - Blood Sampling - before and after the procedure, a small peripheral blood sample (20mL) will be collected into EDTA-coated vacutainers. After the Stem Cell Collection - Interviews (1 hour time commitment) The interviews with donors will focus on: - Perceived acceptability of intra-apheresis cycling (e.g., benefits and challenges). - Physical and emotional experiences during the procedure. - Perceived benefits or burdens of participation. - Suggestions for improving the protocol or participant experience. These interviews will be conducted via an online video service and led by the research associate or chief investigator. Survey If the participant is happy to take part, a series of online questions will be put forward and should take around 10-15 minutes to complete. No identifiable data will be collected, but some special category data, such as age and ethnic origin, will be obtained; this will not be linked to the respondent. Questions will focus on lifestyle, quality of life, perceptions regarding cycling during a stem collection and more general questions about attitudes towards regular exercise. Timeline of Research The broad timetable for the stages of the research includes preparation, convening meetings/conducting interviews, interpreting and analysing findings, and preparing the final report. Other Data sharing statement to be made available at a later date f397731c-b69f-43d2-acb1-28edc0e4ed78 222e31ce-5bf3-4efd-b323-b31c2a6c461d 4eb92b98-b0b3-48b2-9709-fd319bceb583 46f9571f-818b-4ae2-b9e3-a90f58620c24 de778b2a-60cc-4dee-9ea2-8fc17c555808 No Phoebe Cox Public

Research Associate School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham Edgbaston Park Road

Birmingham United Kingdom B15 2TT - p.cox.2@bham.ac.uk Public Alex Wadley https://orcid.org/0000-0002-1820-8446 Principal investigator

Chief Investigator School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham Edgbaston Park Road

Birmingham United Kingdom B15 2TT +44 0121 8011414 a.j.wadley@bham.ac.uk Public - Study Team Public Scientific

School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham Edgbaston Park Road

Birmingham United Kingdom B15 2TT - stemex@contacts.bham.ac.uk Public University of Birmingham Hospital/treatment centre https://ror.org/03angcq70 Non-commercial Academy of Medical Sciences http://dx.doi.org/10.13039/501100000691 15357676 true Evaluating the efficacy of an AI-delivered, neurosymbolic, human-supervised digital intervention for depression and anxiety versus standard cognitive-behavioural therapy in young persons and adults: a pivotal, randomised, controlled, non-inferiority trial To determine whether Nook is non-inferior to standard CBT-based talking therapy in reducing symptoms of depression and/or anxiety at 9 weeks post-randomisation. Background and study aims Depression and anxiety are common mental health conditions that can significantly affect daily life. Cognitive-behavioural therapy (CBT) is an effective treatment, but many people face long waiting times to access it. Nook is an AI-enabled digital programme developed by PsyScale that delivers structured psychological support based on CBT and ACT (Acceptance and Commitment Therapy) through a conversational interface. This study aims to find out whether Nook works as well as standard remote CBT for reducing symptoms of depression and anxiety. Who can participate? Adults and young people aged 16-64 years who have moderate to moderately-severe symptoms of depression and/or moderate to severe anxiety symptoms, sufficient English language skills, and access to an internet-connected device. Participants must not have severe depressive symptoms or high clinical risk. What does the study involve? Participants will be randomly assigned to either use Nook for 6-10 weeks or receive standard remote CBT. They will complete questionnaires about their symptoms at several points during the study. There are no invasive tests or biological samples required. What are the possible benefits and risks of participating? By taking part, participants will be helping to find out what works best for people with anxiety and depression. If Nook is shown to work as well as regular therapy, it could help many people access support faster. As with any therapy, some participants may experience difficult feelings, frustration, or feel worse before feeling better. Additional minor risks include questionnaire burden, fatigue, and difficulty concentrating. There is a small chance Nook could produce an unexpected response, though qualified clinicians monitor the system at all times. Where is the study run from? PsyScale Ltd (UK) When is the study starting and how long is it expected to run for? June 2026 to April 2027 Who is funding the study? PsyScale Ltd (UK) Who is the main contact? Bethan Hawkins, bethan.hawkins@curavit.io Depression and anxiety symptom severity Patient Health Questionnaire (PHQ-9 or PHQ-A) and Generalised Anxiety Disorder 7-item scale (GAD-7) Baseline, 9 weeks post-randomisation Caseness recovery PHQ-9 (or PHQ-A) score <10, and/or GAD-7 score <8 9 weeks Reliable improvement a reduction of ≥6 points on the PHQ-9 (or PHQ-A) and/or ≥4 points on the GAD-7, without a corresponding reliable deterioration on the other measure (assessed only for participants meeting caseness at baseline) 9 weeks Health-related quality of life the EQ-5D-5L (47), a validated, preference-based measure of health-related quality of life that enables estimation of quality-adjusted life years (QALYs) 9 weeks Ethics approval required South Birmingham REC

2 Redman Place, Stratford

London United Kingdom E20 1JQ 26/WM/0050 10.1186/ISRCTN15357676 369133 369133 Interventional Randomized controlled trial Open (masking not used) Active Parallel Treatment Not applicable 2027-04-26T00:00:00.000Z United Kingdom England Lindus Health

Lindus Health - 65 Southwark Street, London, SE1 0HR, United Kingdom

London England SE1 0HR false 1. Have symptoms of generalised anxiety disorder and or symptoms of major depressive disorder as the primary reason for seeking treatment as determined by a psychological well-being practitioner 1.1. Symptoms may meet criteria for either or both disorders 2. Meet symptom severity criteria on either validated screening measure 2.1. Depression assessed using PHQ-9 or PHQ-A for young people with a total score between 10 and 19 corresponding to moderate to moderately severe symptoms 2.2. Anxiety assessed using GAD-7 with a total score between 8 and 21 corresponding to mild to severe symptoms 3. Aged 16 to 64 years 4. If taking psychotropic medication for depression and or anxiety, be on a stable regimen for at least 6 weeks prior to screening with no initiation, discontinuation or dose change during that period 5. Have reliable access to a compatible internet connected device and be able to use it for screening and eligibility, the intervention and assessments with any potential costs clearly noted in the participant information sheet 6. Possess sufficient English language proficiency and cognitive capacity to engage with the digital therapeutic content and complete questionnaires 7. Provide informed consent 8. Be willing to be randomised and to participate in a clinically supervised CBT based AI programme including completion of scheduled outcome assessments Mixed 16 Years 64 Years All 400 0 1. Depression assessed using PHQ-9 or PHQ-A for young people with a total score of 20 or higher 2. Present with a primary or comorbid diagnosis or history that is unsuitable for a digital CBT based intervention as judged by the investigator, including 2.1. Post traumatic stress disorder or complex trauma 2.2. Psychotic disorder, bipolar disorder and or mania 2.3. Complex or treatment resistant obsessive compulsive disorder 2.4. Personality disorder 2.5. Eating disorder 2.6. Substance use disorder or alcohol use disorder 3. Exhibit high risk clinical concerns, including 3.1. Current suicidal ideation with intent or plan as indicated by PHQ-9 score and or participant disclosure 3.2. Suicide attempt within the past 12 months 3.3. Ongoing self harming behaviours 3.4. Requirement for urgent or crisis mental health intervention as indicated by PHQ-9 score and or participant disclosure 4. In participants aged 25 years and under, current treatment with an antidepressant medication that was initiated or dose adjusted within the past 12 weeks due to the recognised increased risk of suicidal thoughts and behaviours during the early phases of antidepressant treatment in this age group 5. Have been referred to or managed by a mental health crisis intervention team or equivalent, or admitted as an inpatient within psychiatric services in the last 12 months 6. Are currently receiving structured psychological therapy for anxiety or depression delivered by another provider 7. Use of medications indicative of severe mental illness or clinical instability, including 7.1. Antipsychotic medication excluding low dose use for non psychiatric indications where clinically appropriate 7.2. Regular use of sedative hypnotic medication such as daily benzodiazepines or Z drugs suggesting clinical instability 7.3. Current or recent use within the past 3 months of psychedelic assisted therapy involving substances such as MDMA, psilocybin or ketamine, where this indicates ongoing clinical instability or participation in an active interventional mental health treatment 8. Participation in another interventional clinical trial or use of investigational drugs in the last 30 days 9. Any other significant disease or disorder which, in the opinion of the investigator, may put the participant at risk because of participation in the trial, influence the results of the trial, or affect the participant’s ability to participate in the trial 2026-06-02T00:00:00.000Z 2026-11-30T00:00:00.000Z Depression and anxiety (Generalised Anxiety Disorder and/or Major Depressive Disorder) Mental and Behavioural Disorders Arm 1 – Nook (Investigational Device): Participants will receive access to Nook, a clinician-supervised, AI-enabled digital psychological intervention developed by PsyScale. Nook delivers structured, evidence-based psychological content derived from Cognitive Behavioural Therapy (CBT) and Acceptance and Commitment Therapy (ACT) via an interactive, text-based conversational interface, supplemented by guided exercises and audio components. The programme consists of four core therapeutic modules (Values and Behavioural Activation, Cognitive Defusion, Sleep and Circadian Regulation, and Graded Exposure), delivered in a fixed sequence, followed by a consolidation and relapse-prevention module. Typical intervention duration is 6–10 weeks, with sessions approximately two times per week and an average session length of 20–25 minutes. Nook is delivered via mobile app, web browser, or tablet under ongoing clinician supervision. Arm 2 – Standard CBT (Control): Participants will receive standard cognitive-behavioural therapy delivered remotely by a qualified therapist for 9 consecutive weeks, representing the current standard of care for depression and/or anxiety. Both arms will be compared on clinical outcomes to assess the non-inferiority of Nook relative to standard CBT. Participants will be randomised in a 1:1 ratio and is stratified by age (16-17, 18-21, 22-64) to ensure balanced allocation across clinically and regulatorily meaningful developmental groups. Updated 15/09/2026: Participants will be randomised in a 1:1 ratio and is stratified by age (16-17, 18-64) to ensure balanced allocation across clinically and regulatorily meaningful developmental groups. Device Not Applicable NOOK Not expected to be made available eb787f0e-b2b2-44a8-bfe2-85723ea69b08 3b54e4e4-a0cd-438d-9a90-8485bcac7209 0d003cb8-98fd-4199-9eae-7f3a18ffe43a ad4e1512-0d66-484c-8f59-e20168b47cda 8ee03380-8fe0-4af8-a143-a4452d65aaca No Bethan Hawkins Public

Lindus Health - 65 Southwark Street

London United Kingdom SE1 0HR +44 808 258 7706 bethan.hawkins@curavit.io Public Marcos Economides https://orcid.org/0000-0003-0511-5432 Scientific

86-90 Paul Street

London United Kingdom EC2A 4NE +44 7902 241486 marcos.economides.ext@psyscale.ai Public Anita Phung https://orcid.org/0009-0001-9137-9727 Principal investigator

Lindus Health - 65 Southwark Street

London United Kingdom SE1 0HR +44 7367 146344 anita.phung@curavit.io Public PsyScale Ltd Commercial PsyScale Ltd