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

NHSBT Newcastle Blood Donor Centre Holland Drive

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

Pinewood House Pinewood PLACE

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

Bethlem Royal Hospital Monks Orchard Road

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

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

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

Robert Dolan House 9 Alie Street

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

Trust Headquarters 350 Euston Road Regents PLACE

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

NHS Foundation Trust Carholme Court Long Leys Road

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

Trust Hq Swandean Arundel Road

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

Carew House Beacon Technology Park Dunmere Road

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

Trust Headquarters Redesmere The Countess of Chester Health Park Liverpool Road

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

Trust Headquarters West Park Hospital Edward Pease Way

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

Harper Lane Shenley

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

Goodmayes Hospital 157 Barley Lane

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

18 Mole Business Park Randalls Road

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

Springfield Hospital 61 Glenburnie Road

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

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

London United Kingdom SE5 8AF +44 (0)20 7848 0002 rory.sheehan@kcl.ac.uk Public South London and Maudsley NHS Foundation Trust https://ror.org/015803449 Non-commercial National Institute for Health and Care Research http://dx.doi.org/10.13039/501100000272 43999465 true A three-arm clustered randomised-controlled superiority trial to compare the effect of a weekly community mobile greengrocer stop (with and without provision of monetary vouchers) versus comparator on fruit and vegetable intake in social housing communities in Liverpool, UK SCHOUSE To compare differences in fruit and vegetable intake after 26 weeks between: A. A comparison group who receive signposting to support and community food initiatives (Comparator), and a group who additionally receive a new weekly mobile greengrocer stop in their neighbourhood (Intervention 1) for 26 weeks, and B. Intervention 1 and a group who receive provision of weekly vouchers for use at the greengrocer in addition to a new weekly mobile greengrocer stop in their neighbourhood (Intervention 2) for 26 weeks Background and study aims Eating a healthy diet can be difficult. Most people in the UK struggle to eat the five recommended portions of fruit and vegetables per day. Not eating enough fruit and vegetables can increase the risk of health problems related to a low-quality diet. Because of this, it is important to understand the barriers people face to eating enough fruit and vegetables. In many communities, it is hard to get to shops and food outlets that sell fruit and vegetables at an affordable price. These issues of access and affordability can create significant barriers to eating a diet that promotes good health. In the UK, people living in social housing are particularly vulnerable to these barriers and the health risks that can result from them. This may be because of the food environment of the community they live in or additional challenges or disadvantages they already face. At present, there is little evidence on what can be done to improve access to and affordability of fruit and vegetables to support people to improve their diet when they live in social housing. Our clustered randomised control trial addresses this gap in evidence, by investigating what happens to people's diet and wellbeing when you introduce a new mobile greengrocer service to their area and what further impact providing vouchers to spend at the mobile greengrocer might have. Who can participate? Adults living in one of our 12 study areas in Liverpool and living in social housing provided by Onward, Riverside, or Torus. They must be 18 years or older, the person responsible for getting food for their household, and not currently in receipt of Rose vouchers from the Alexandra Rose Charity. What does the study involve? We will randomly allocate our 12 study areas to one of three groups. Participants in an area will receive new initiatives based on which group their area was allocated to for the duration of the 6-month trial. Participants from areas in Group 1 will receive monthly, digital bulletins from their housing provider, outlining local opportunities for support, upcoming events, and community-based food initiatives. Participants from areas in Group 2 will receive monthly bulletins, like participants in Group 1, but they will also receive the opportunity to shop at a new mobile greengrocer service within 1km of where they live. The mobile greengrocer will visit their area at the same time every week for 6-months and will sell fresh fruit and vegetables to anyone in the community who would like to shop there. Participants from areas in Group 3 will receive monthly bulletins and the opportunity to shop at a new mobile greengrocer service within 1km of where they live, like participants in Group 2. In addition to this, they will also receive vouchers to spend on fruit and vegetables at the mobile greengrocer each week. The participants will receive these vouchers for 6-months. Participants in all areas will complete a questionnaire and three online 24-hour food diaries at the beginning, middle, and end of the trial. Our main outcome of interest is fruit and vegetable intake. We want to see if (i) introducing a weekly mobile greengrocer stop to a local area supports people to increase their fruit and vegetable intake, and (ii) pairing this introduction with provision of vouchers to spend at the new service supports people to increase their fruit and vegetable intake even more than introducing the new service alone. We will also explore other outcomes that might help to understand how introducing this new service and voucher provision may work, for example, mental health and wellbeing, sense of community and social support, and barriers to doing food shopping and accessing fresh fruit and vegetables. What are the possible benefits and risks of participating? People who take part will help support the trial's aim to develop an understanding of how community-based approaches to improve the access and affordability of fresh food can impact people living in social housing. By actively engaging in the new offers delivered in the trial, participants will likely improve the chances that their areas continue to be supported by these offers in the longer term. Participants who complete the trial questionnaires and food diaries across the course of trial will receive retail vouchers as compensation for their time. While there very few risks in taking part, some participants may find it uncomfortable to answer questions about their experiences and challenges around getting food, finances, health, and wellbeing. Where is the study run from? The trial is mainly being delivered by researchers at the University of Liverpool, UK, with support from researchers at the University of Cambridge, UK. We are also collaborating with three housing associations (Onward Homes, Riverside, and Torus) who together manage the majority of social housing properties in Liverpool. When is the study starting and how long is it expected to run for? The trial is starting on Monday 7th September 2026 and is expected to be complete by the end of August 2027. Who is funding the study? The trial is supported by the UK Research and Innovation (UKRI) Strategic Theme on Creating Opportunities, Improving Outcomes, in partnership with UKRI’s Global Food Security programme (UKRI GFS), BBSRC, AHRC, ESRC, MRC, NERC and Innovate UK. Who is the main contact? Dr Courtney Neal, courtney.neal@liverpool.ac.uk Average daily fruit and vegetable intake (g) at endpoint 3 x 24h dietary recalls via Intake24 baseline and week 22 Average daily fruit and vegetable intake (g) at midpoint 3 x 24h dietary recalls via Intake24 baseline and week 11 Average daily portions of fruit and vegetables consumed 3 x 24h dietary recalls via Intake24 baseline, week 11, and week 22 Average daily intake of energy (kcal) 3 x 24h dietary recalls via Intake24 baseline, week 11, and week 22 Average daily intake of carbohydrates (g) 3 x 24h dietary recalls via Intake24 baseline, week 11, and week 22 Average daily intake of protein (g) 3 x 24h dietary recalls via Intake24 baseline, week 11, and week 22 Average daily intake of fat (g) 3 x 24h dietary recalls via Intake24 baseline, week 11, and week 22 Average daily intake of AOAC fibre (g) 3 x 24h dietary recalls via Intake24 baseline, week 11, and week 22 Daily portions of fruit and vegetables consumed by eldest child in household a parent-reported food frequency question in questionnaire baseline, week 11, and week 22 Food insecurity status U.S. Adult Food Security Module (10-items) with a 30-day reference period baseline, week 11, and week 22 Use of emergency food support a self-reported frequency question in questionnaire baseline, week 11, and week 22 Use of community food projects a self-reported frequency question in questionnaire baseline, week 11, and week 22 Barriers to buying, cooking and eating fresh fruit and vegetables a self-reported question in the questionnaire baseline, week 11, and week 22 Household weekly spend on fresh fruit and vegetables a self-reported question in the questionnaire baseline, week 11, and week 22 Frequency of Queen of Greens use at a stop <1km from home address in last three months a self-reported question in the questionnaire baseline, week 11, and week 22 Frequency of Queen of Greens use at a stop >1km from home address in last three months a self-reported question in the questionnaire baseline, week 11, and week 22 Self-efficacy in affording the fruit and vegetables needed for their household to eat a healthy diet a self-reported question in the questionnaire baseline, week 11, and week 22 Liking of eating fresh fruit a self-reported, VAS question in the questionnaire baseline, week 11, and week 22 Liking of eating fresh vegetables a self-reported, VAS question in the questionnaire baseline, week 11, and week 22 Negative emotional state Depression, Anxiety and Stress Scale - 21 items (DASS-21) in the questionnaire baseline, week 11, and week 22 Severity of depression symptoms the depression sub-scale of DASS-21 in the questionnaire baseline, week 11, and week 22 Severity of anxiety symptoms the anxiety sub-scale of DASS-21 in the questionnaire baseline, week 11, and week 22 Severity of stress symptoms the stress sub-scale of DASS-21 in the questionnaire baseline, week 11, and week 22 Feelings of loneliness the three-item UCLA loneliness scale and a direct measure of loneliness (recommended by the Office for National Statistics) in the questionnaire baseline, week 11, and week 22 Level of social support the Oslo Social Support Scale (OSSS) in the questionnaire baseline, week 11, and week 22 Sense of community the Brief Sense of Community Scale (BSCS) in the questionnaire baseline, week 11, and week 22 Satisfaction with housing provider three items from the Tenant Satisfaction Measures (TSM; overall satisfaction, feeling the housing provider listens to them and acts on their needs, and being satisfied that housing provider positively contributes to their neighbourhood) baseline, week 11, and week 22 Support service use a self-reported question in the questionnaire baseline and week 22 Daily portions of fruit and vegetables a self-reported food frequency question in the questionnaire baseline, week 11, and week 22 Ethics approval required University of Liverpool Central University Research Ethics Committee C

Foundation Building University of Liverpool

Liverpool United Kingdom L69 7ZX 18413 10.1186/ISRCTN43999465 Interventional Randomized controlled trial Open (masking not used) Active Cluster Treatment Not applicable 2027-08-31T00:00:00.000Z United Kingdom England University of Liverpool

Department of Public Health, Policy and Systems Institute of Population Health University of Liverpool Brownlow Hill

Liverpool England L69 3GB true 1. Aged 18 years old or over 2. Living in one of the 12 clusters 3. Live in a property managed by Onward Homes, Riverside or Torus 4. Be the primary food procurer for their household Mixed 18 Years 125 Years All 360 0 1. Currently in receipt of Rose vouchers provided by the Alexandra Rose Charity 2026-09-07T00:00:00.000Z 2027-03-30T00:00:00.000Z Fruit and vegetable intake of people living in social housing Other As we are conducting a clustered randomised controlled trial, we will randomise at the cluster level. In the present trial, each of our 12 trial sites is a cluster. Thus, participants will be allocated to groups depending on the trial site that they live in. We will randomise the 12 sites to the three intervention arms in blocks of four using the randomizr package in RStudio. Each of the four blocks will correspond to the four waves of trial rollout. The sites in the first block (as determined by the order of the randomisation list) will become the sites in the first wave, and so forth for the following blocks and waves. Comparator (Signposting) The comparator condition for the trial is similar to “usual care”. It is typical for housing associations, through direct communication with dedicated housing officers or health and wellbeing staff, to provide signposting to their tenants about community food initiatives they can access. If required, they may provide referrals for specific projects (i.e., food bank referrals). They also provide signposting to welfare and benefits advice, debt support and other forms of financial support via newsletters and social media. During the trial, partner housing associations will proactively provide this information to all participants (who are also their customers) every four weeks in the form of bulletins via email or WhatsApp. When participants sign up for the trial, they will consent to receive this information. The bulletins will be provided to all participants in the study for 26 weeks. However, participants in the Comparator arm will not receive any other interventions beyond the bulletins. The research team will contact participants in this arm on the Monday before the trial begins to inform them which arm their site is in and what to expect. Intervention 1 (Signposting + Mobile greengrocer) The Queen of Greens is a mobile greengrocer service running a timetable of weekly stops across Liverpool and Knowsley in the North West of England. It sells fresh fruit and vegetables, purchased fresh from the wholesaler, from converted buses/vans which double up as a mobile shops that customers can get on board to do their shopping. Anyone can shop at the Queen of Greens and they accept Healthy Start vouchers and Alexandra Rose vouchers at all of their stops. In addition to receiving the bulletins outlined above, the Queen of Greens bus will begin making weekly stops in sites randomised to Intervention 1. The new stop will be within 1 km of participants' homes. In the first week of the trial, participants will be encouraged to visit the Queen of Greens bus to receive a free tote bag. Participants who are unable to collect the tote bag from the bus in this first week will have the tote bag delivered to their home address. To encourage repeat shopping on the bus, each tote bag will contain a stamp card. Each time a participant shops on the bus in the following weeks and brings their tote bag to put carry their shopping in, they will receive a stamp on their stamp card from the bus' driver after they have made their purchase. They will be able to collect a maximum of one stamp per week, up to a maximum of four stamps. Once they have filled their stamp card, they will receive a monetary voucher to spend on the bus the following week (with an approximate value of up to £5). Vouchers must be spent before Week 8 of the trial, to minimise the impact that the spending of the voucher has on midpoint dietary measures. The bus will be at each stop for 45 min to 1 h per week in each site. With the exception of a two week break over the Christmas and New Year period when the wholesaler closes, the Queens of Greens bus will stop at the same time every week for 26 weeks as part of the trial. It will be at the Queen of Greens' discretion as to whether they continue these stops after the trial concludes. On the Monday before the trial wave begins, the research team will contact participants to tell them about the new Queen of Green stop and provide information about the Queen of Greens and the tote bag/stamp card incentive. Participants will also be invited to follow the Queen of Greens on social media to receive updates on any changes to timetables or schedules. In the bulletin from their housing association, participants will receive a reminder of the date and time the Queen of Greens will be stopping. In summary, the Queen of Greens mobile greengrocer will: • Stop at a regular time and place for 45-60 min each week in intervention site locations, • Enable customers to buy fruit and vegetables on the bus priced in 50p increments, • Not require membership or regular use, • Make pricing clear per each type of item, • Keep customers up to date via their social media on timetable changes, • Take customer preferences and requests into account, • Manage the queue so that the bus is not too crowded with customers (i.e., only 3 people on the bus at a time), • Occassionally provide bundles of free, fresh herbs for customers, and • Occasionally provide free recipe cards for customers. Intervention 2 (Signposting + Mobile greengrocer + Fruit and vegetable vouchers) Alexandra Rose Charity is a charity which provides vouchers (Rose vouchers) to purchase fresh fruit and vegetables from market traders. In addition to receiving everything in Intervention 1 (bulletins and new weekly Queen of Greens stop in their area), participants in sites randomised to Intervention 2 will receive Rose vouchers to purchase fresh fruit and vegetables at the Queen of Greens. Participants will receive one batch of four bundles of vouchers by postal delivery every four weeks (one bundle per week) for the duration of the trial. Over the 26 week trial, participants will receive a total of 7 batches – 6 deliveries with 4 bundles (24 weeks of vouchers) and 1 delivery with 2 bundles (2 weeks of vouchers). Each bundle will include a flyer/note indicating when the participant can expect their next bundle of vouchers. Whether Rose vouchers are hand-delivered to a participant’s address or sent via the postal system depends on the approach their housing association chooses. We will encourage weekly use, but participants will have at least four weeks to use the vouchers they receive in a delivery. Each participant will receive £6 of Rose vouchers per week, plus an additional £2 for each additional member of their household; thus, the weekly value of vouchers each participant receives will vary by their household size. We will assess household size using the number of children and adults participants report being “usually” part of their household in the baseline questionnaire (“usually” is defined as staying with them for 2 or more nights per week). We will not verify household size and composition with the housing associations, as we expect participants to respond honestly to these questions, given their knowledge of the housing associations' involvement in the trial. Researchers will be responsible for registering participants on Alexandra Rose Charity's system, but housing association staff will be responsible for distributing Rose vouchers to participants who due to receive Intervention 2 and who are also their customers. On the Monday before the trial wave begins, the research team will contact participants to inform them that they will receive vouchers to spend at Queen of Greens for the duration of the trial and explain how the distribution and redemption of the vouchers will work. If participants indicate that they no longer want to participate in the trial, they will no longer receive vouchers. Otherwise, vouchers will continue to be sent to participants, even if (i) there is evidence that participants are not using them and/or (ii) participants do not complete a study midpoint or endpoint questionnaire or dietary recall. In summary, Rose vouchers: • Can only be redeemed on the Queen of Greens mobile greengrocer in Liverpool and the surrounding areas (they are not accepted elsewhere), • Should only be spent by the household to which they are issued, • Are paper vouchers that are tracked; if lost and not spent, can be voided, and new vouchers can be issued, • Are only available in £1 denominations and the whole £1 must be redeemed at once (at the Queen of Greens, products are priced in multiples of 50p, so a participant can spend the full value of each voucher), • Have a ‘use by’ date, which is roughly one month after the voucher is issued (while this is not strictly enforced, it is in place to encourage regular spending), • Are scanned ‘out’ by the issuing authority (e.g., housing associations) and scanned ‘in’ by the retailer on use (e.g., Queen of Greens), enabling voucher use to be tracked and retailers to claim payment for the vouchers received from Alexandra Rose. ------- A note on timings The Queen of Greens are unable to operate over the Christmas and New Year period (approximately Monday 21st December 2026 - Monday 4th January 2027) as there wholesale supplier closes for this duration. Further, there is likely to be a significant reduction in staffing capacity from the housing associations during this period which will significantly hinder trial delivery. For any sites in trial waves which include this period, we will treat this two-week period as a pause in the trial in all sites, regardless of allocation. Thus, we will not distribute bulletins in this period, nor will the Queen of Greens visit sites allocated to Intervention 1 or 2. In sites which are affected by this pause, we will extend the trial by two weeks and treat the pause in intervention delivery as a pause in the trial timeline (i.e., midpoint and endpoint data collection will also be pushed back by two weeks). However, to minimise harm that may result from an abrupt stop to Rose vouchers provision, we will provide any participants receiving Rose vouchers with two weeks' worth of vouchers to spend the week before the break in Queen of Greens' provision along with clear guidance on when they can be spent before and after the break. Behavioural The anonymised datasets generated during and/or analysed during the current study will be stored indefinitely in a publicly available repository, the University of Liverpool's Data Catalogue (https://datacat.liverpool.ac.uk/), after an embargo period from the date of data collection to allow for the publication of research findings. Access to the data will be able to be requested from the study Principal Investigator. Anonymised data from questionnaires and 24 h dietary recalls will be available following an embargo period to allow for publication of the research findings. We expect this will be approximately 1 year following the completion of data collection. Explicit consent will be obtained from participants to enable to the public sharing of their anonymised data. Stored in publicly available repository Protocol

Consent form

b208a79c-52ee-40db-bebf-6ab067711426 533e163f-c39e-43e9-81b5-9285dd977e55 743ec8cd-cc72-4709-b855-08ea2757a952 3bd2a8b5-d6b2-461d-9ddc-98f3c0fd1515 Yes Consent form 50184 Consent_SCHOUSE Trial v5 04Aug2026.pdf 1f19a5f7-e9b0-49a6-9535-3e5367b35648 true application/pdf 117441 9aa14e964e174d4be2ee1ede178923be Participant information sheet 50184 PIS_SCHOUSE Trial v7 04Aug2026.pdf 941a48c6-928f-4cbd-b968-2d802e34b659 true application/pdf 459646 509f98678b835e3a6323bde3d46c7c0c Protocol file 50184 Protocol_SCHOUSE Trial v2 28Aug2026.pdf 7ea5492b-5a27-4f56-9649-590c6c733cb6 true application/pdf 1249911 872b651a245f54a650915c731089a29e Rachel Loopstra https://orcid.org/0000-0002-7541-6209 Principal investigator

Department of Public Health, Policy and Systems University of Liverpool

Liverpool United Kingdom L69 3GB +44 7345 442688 rachel.loopstra@liverpool.ac.uk Public Courtney Neal https://orcid.org/0000-0001-5507-4849 Scientific Public

Department of Public Health, Policy and Systems University of Liverpool

Liverpool United Kingdom L69 3GB +44 7345 442688 courtney.neal@liverpool.ac.uk Public University of Liverpool https://ror.org/04xs57h96 Non-commercial UK Research and Innovation http://dx.doi.org/10.13039/100014013 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 59787438 true VR-assisted nature therapy versus online stress management: a randomised controlled trial To evaluate the feasibility, acceptability, and preliminary effectiveness of Thrive Inside, a 12-week VR-assisted nature-based digital therapeutic intervention, compared with an established online stress management programme for adults experiencing stress and anxiety. The study also aimed to inform the design and implementation of a future definitive randomised controlled trial. Background and study aims Stress and anxiety affect millions of people in the UK and are among the most common reasons for seeking mental health support. Long waiting times and increasing demand mean that many people do not receive help as quickly as they need it. There is therefore growing interest in developing accessible interventions that can support people experiencing stress and anxiety before symptoms become more severe. Research has shown that spending time in nature may improve mental wellbeing. Virtual reality offers a way of delivering immersive nature-based experiences in a controlled and accessible way, enabling people to engage with therapeutic environments regardless of weather, location or mobility. Thrive Inside is a 12-week digital programme developed by EarthscapeVR that combines nature-based experiences, psychological education, breathing exercises, mindfulness and guided activities. Some participants also attend facilitated VR sessions using immersive nature environments. The aim of this study is to evaluate whether Thrive Inside is practical and acceptable to deliver, and to compare it with an established online stress management programme based on cognitive behavioural principles. The study will also help determine whether a larger clinical trial should be undertaken in the future. Who can participate? Adults aged 18 to 66 years living in the United Kingdom who were experiencing mild to moderate symptoms of stress or anxiety What does the study involve? People interested in participating contacted the research team after seeing information about the study through TalkHealth and other recruitment materials. Those who met the eligibility criteria received detailed information about the study and provided informed consent before taking part. Participants were randomly allocated to one of two groups. The intervention group completed Thrive Inside, a 12-week online programme consisting of weekly learning modules, breathing exercises, mindfulness practices, nature-based activities and guided reflective exercises. Participants were also invited to attend three facilitated virtual reality sessions using immersive natural environments. Where attendance was not possible, equivalent two-dimensional (2D) video content was provided online. The comparison group completed an established online stress management programme based on cognitive behavioural principles over the same 12-week period. They also received access to an NHS mindfulness body scan exercise. Participants in both groups completed questionnaires before the programme began, during the intervention and after completing the programme. These questionnaires assessed stress, anxiety, mental wellbeing, life satisfaction and connectedness to nature. Participants also provided feedback about their experience of taking part. What are the possible benefits and risks of participating? Participants may learn techniques that help them manage stress, improve emotional wellbeing and develop healthy coping strategies. However, individual benefits cannot be guaranteed. The study was considered low risk. Some participants may have experienced temporary emotional discomfort when completing questionnaires or reflecting on their wellbeing. Participants using VR could also experience mild side effects such as dizziness, eye strain or motion sickness. Participants were free to stop using the VR equipment or withdraw from the study at any time without giving a reason. Information about additional support services was available during study and afterwards. Where is the study run from? The study was sponsored and coordinated by EarthscapeVR Ltd in the United Kingdom. Recruitment was carried out primarily through TalkHealth, with participants completing most aspects of the study remotely from home. The study was conducted in collaboration with researchers from Birkbeck, University of London, the University of Liverpool and the University of Vienna (Austria). When is the study starting and how long is it expected to run for? November 2024 to August 2025 Who is funding the study? The study was funded by Innovate UK, part of UK Research and Innovation (UKRI), through the Creative Catalyst programme (Grant No. 10117269). EarthscapeVR Ltd also provided the intervention platform, virtual reality content and study resources. Who is the main contact? Dr Annahita Nezami, annahita@earthscapevr.com Perceived stress the Perceived Stress Scale (PSS-10) baseline Week 0, mid-intervention (around weeks 3 - 6), and post-intervention (around week 14) Anxiety symptoms Generalized Anxiety Disorder-7 (GAD-7) baseline Week 0, mid-intervention (around weeks 3 - 6), and post-intervention (around week 14) Mental well-being the Warwick–Edinburgh Mental Well-being Scale (WEMWBS) baseline Week 0, mid-intervention (around weeks 3 - 6), and post-intervention (around week 14) Life satisfaction the Satisfaction With Life Scale (SWLS) baseline Week 0, mid-intervention (around weeks 3 - 6), and post-intervention (around week 14) Nature connectedness the Nature Relatedness Scale-6 (NR-6) baseline Week 0, mid-intervention (around weeks 3 - 6), and post-intervention (around week 14) Ethics approval required London - West London & GTAC Research Ethics Committee

Health Research Authority, 2 Redman Place, Stratford

London United Kingdom E20 1JQ 24/LO/0670 10.1186/ISRCTN59787438 345992 345992 Interventional Randomized controlled trial Blinded (masking used) Active Parallel Prevention Treatment Not applicable 2025-08-01T00:00:00.000Z United Kingdom England Talkhealth Partnership Limited

Landmark House, Station Road

Hook England RG27 9HA false 1. Aged 18-66 years 2. Able to provide written informed consent 3. Able to understand English sufficiently to provide written informed consent and understand the written content of the course (alternative language versions are planned for future versions of both the online course and VR content 4. Are aware of ongoing symptoms of mild-moderate anxiety or stress, e.g., over-worrying, nervousness, irritability, mood swings, difficulty concentrating, feeling overwhelmed, exhaustion, negative thoughts, avoidance or withdrawal from usual activities, appetite changes, sleep disturbances, and/or changes in routine 5. Have access to a laptop, mobile phone, or tablet with an internet connection to participate in the online course. The course is designed to be user-friendly and accessible across multiple devices, promoting greater inclusivity Mixed 18 Years 66 Years All 60 74 1. No history of serious self-reported psychiatric or medical conditions 2. No current self-reported serious psychiatric symptoms, such as psychosis or eating disorders 3. No significant issues with vision and/or hearing loss 4. A diagnosis of, or chronic symptoms related to, anxiety disorders such as social anxiety, agoraphobia, health anxiety, panic disorder, or obsessive-compulsive disorder 2024-11-08T00:00:00.000Z 2025-01-31T00:00:00.000Z Mild-to-moderate levels of stress or anxiety Mental and Behavioural Disorders Participants were allocated to either the Thrive Inside intervention group or the active control group after informed consent and enrolment. Microsoft Excel was used to generate a random allocation sequence using the binary values 0 and 1, with 0 representing the control group and 1 representing the Thrive Inside group. Each participant on the enrolment list was assigned to the corresponding value in the randomised sequence. The resulting allocation determined the participant’s study group. The intervention group received Thrive Inside, a 12-week multimodal digital therapeutic programme combining immersive virtual nature experiences, psychoeducation, mindfulness-based exercises, therapeutic activities, and optional group-based VR sessions designed to promote stress reduction, emotional regulation, and nature connectedness. Participants who were unable to attend immersive sessions accessed equivalent two-dimensional (2D) content remotely. The comparator group received an established online stress management programme based on cognitive behavioural principles, delivered over the same 12-week period. Behavioural An anonymised participant-level dataset, study protocol, statistical analysis code and supporting documentation will be deposited in the Open Science Framework (OSF) repository following publication. The data will be made available indefinitely for research purposes. All shared data will be anonymised in accordance with UK GDPR, participant consent and ethical approval. OSF Link https://osf.io/nd8zg/overview?view_only=a494ae5ae57441159d1103c9881467be Stored in publicly available repository Protocol

8e94cc6a-9d0f-447e-9819-58219cd13d2e a04348fc-aa18-4be8-868c-43e7f97b70ea 729c244a-7cc7-4d38-ad47-ab5c31c5bf11 Yes Annahita Nezami https://orcid.org/0009-0003-9705-758X Principal investigator Scientific Public

71-75, Shelton Street, Covent Garden

London United Kingdom WC2H 9JQ - annahita@earthscapevr.com Public EarthscapeVR LTD Commercial Innovate UK http://dx.doi.org/10.13039/501100006041 88133553 true ReSET – Rechallenge Staphylococcus aureus Experimental nasal colonisation sTudy ReSET Primary objectives: Stage I: To determine the safety of S. aureus primary challenge in humans Stage I co-primary: To determine the challenge doses required to achieve a 50-70% nasal colonisation rate with up to two strains of S. aureus Stage II: To determine the safety of S. aureus primary challenge and rechallenge in humans Stage II co-primary: To quantify the rate of S. aureus acquisition following primary challenge, homologous rechallenge ± heterologous rechallenge Secondary objectives: 1. To explore immunological and microbiological markers including those induced by S. aureus exposure and how those may predict protection against re-infection 2. To describe pre-decolonisation S. aureus carriage within the study population 3. To determine time-course and bacterial density of colonisation with challenge strains 4. To determine rates and extent of colonisation spread to extra-nasal sites with challenge strains Background and study aims Staphylococcus aureus is a common bacterium that many people carry in their noses without feeling unwell. In some people it can lead to infections, but we do not fully understand why it lives harmlessly in some individuals and not others. This study aims to learn more about how the bacterium settles in the nose and whether being exposed once can protect someone from becoming colonised again in the future. To do this, the study team will place a small, carefully measured amount of the bacterium into the noses of healthy adult volunteers and monitor them closely. Who can participate? Healthy adults aged 18 to 55 years who meet the detailed health and lifestyle criteria set by the study team. What does the study involve? Participants will first attend a screening visit, where their general health will be checked. If eligible, they will then complete a standard 5 day course of decolonisation treatment that includes a nasal antibiotic ointment and an antiseptic hair and body wash. About two weeks later, they will return to receive the challenge, which means a small amount of Staphylococcus aureus will be dripped into their nose. Participants will record any symptoms each day for 28 days, with some days involving in-person visits for safety checks, blood tests and nose or body swabs. They will take some nose samples at home using equipment provided. After this follow-up period, they will repeat the decolonisation treatment. Some participants may be invited to take part in a second challenge later in the study, depending on whether they became colonised the first time. What are the possible benefits and risks of participating? Participants will be contributing to important research that may help scientists develop new ways to prevent or treat Staphylococcus aureus infections in the future. However, taking part carries some risks. Mild infections such as small skin spots or pimples can occur, though more serious infections are uncommon in healthy adults. There is a small chance volunteers could pass the bacteria to others, so they must avoid close contact with vulnerable people for a period of time. Blood tests may cause slight pain or bruising, and nasal swabs can be a little uncomfortable. The decolonisation products may cause mild irritation or, rarely, allergic reactions. Antibiotics will only be used if necessary. Where is the study run from? The study is run in Oxford, United Kingdom, at the Centre for Clinical Vaccinology and Tropical Medicine at Churchill Hospital. When is the study starting and how long is it expected to run for? April 2026 to December 2029. Who is funding the study? Ellison Institute of Technology (UK) Who is the main contact? Mr Conor Whelan at the Centre for Clinical Vaccinology and Tropical Medicine in Oxford. conor.whelan@paediatrics.ox.ac.uk Stage I: Occurrence of solicited and unsolicited adverse events, serious adverse events and adverse events of special interest clinical assessment and safety reporting D0–D6 (solicited), D0–D28 (unsolicited), study duration (SAEs & AESIs) Stage I: Presence of Staphylococcus aureus in nasal wash culture based microbiology D3–D10 Stage II: Occurrence of solicited and unsolicited adverse events, serious adverse events and adverse events of special interest clinical assessment and safety reporting D0–D6 (solicited), D0R1–D6R1, D0–D28, D0R1–D28R1 (unsolicited), study duration (SAEs & AESIs) Stage II: Presence of Staphylococcus aureus challenge strain in nasal wash culture based microbiology D3–D28, D3R1–D28R1 Ethics approval required South Central - Berkshire REC

2 Redman Place, Stratford

London United Kingdom E20 1JQ 26/SC/0123 10.1186/ISRCTN88133553 366748 CPMS: 71824 366748 71824 Interventional Randomized controlled trial Open (masking not used) Active Parallel Treatment Not applicable Treatment 2029-12-31T00:00:00.000Z United Kingdom England Oxford Vaccine Group

Old Road Headington

Oxford England OX3 7LE Liverpool Vaccine Group

Liverpool School of Tropical Medicine, Accelerator Building, 1 Daulby Street

Liverpool England L7 8XZ 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 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 true 1. Adults between 18 to 55 years old (inclusive) at the time of enrolment (defined by the start of first decolonisation therapy) 2. Medically healthy, such that according to investigator judgement, hospitalisation within the study period is not anticipated, and the participant appears likely to be able to remain a study participant through to the end of protocol-specified follow-up. Planned elective procedures for pre-existing conditions may be allowable if S. aureus colonisation is not deemed to put the participant at increased risk of harm and if the elective procedure does not routinely involve, and is not likely to involve, decolonisation and/or antibiotic therapy 3. Fluent spoken English – to ensure a comprehensive understanding of the research project and their proposed involvement 4. Capacity to provide written informed consent in English for participation in the study 5. Able to attend the scheduled visits and to comply with all study procedures, including internet access for the recording of electronic diaries after issue of decolonisation therapy and S. aureus challenge 6. Able to follow and adhere to hygiene advice as well as the decolonisation protocol which includes daily shower and hair wash 7. Willing and able to avoid planned, non-essential non-study antibiotics for the duration of the study 8. Willing and able to avoid intranasal and inhaled products (including nasal steroids) unless prescribed by the study team for the duration of the study 9. Able to adhere to standard hygiene advice at home 10. Willing to allow confirmation of past medical history either through provision of, or access to, a medical record summary or other medical documentation or to allow investigators to obtain a copy of their medical history via their GP practice or via electronic patient records 11. Willing to allow their GP and/or consultant, if appropriate, to be notified of participation in the study 12. Willing to provide their national insurance number or passport number to be registered on The Trial Over-Volunteering Prevention System (TOPS) 13. For participants of childbearing potential only: Willing to use effective contraception for the duration of the study AND to have a pregnancy test on the day of screening, and challenge or as indicated by the study doctor Adult 18 Years 55 Years All 384 0 1. Research participants 1.1. Participation in another research study in which procedures could compromise the integrity of this study (for example immune modulating or stimulating treatments) or the safety of the participant (for example significant volumes of blood taken), or planning to do so within the study period 2. Vaccination (self-reported with or without confirmation from GP questionnaire or medical records or summary if deemed necessary at clinician discretion) 2.1. Planned vaccination in the two months following final challenge 2.2. Live vaccination within the 4 weeks prior to first challenge 3. Allergy 3.1. Have an allergy or intolerance to beta-lactam antibiotics 3.2. Have an allergy or intolerance to more than one of doxycycline, co-trimoxazole, clindamycin and linezolid 3.3. Have an allergy or intolerance to any of the agents used for decolonisation 4. Specific health history (self-reported with or without confirmation from GP questionnaire or medical records or summary if deemed necessary at clinician discretion) 4.1. History of severe S. aureus infection, including PVL-associated disease 4.2. Atopic dermatitis 4.3. Psoriasis, eczema or other chronic skin condition requiring treatment in the last year 4.4. Compromised skin barrier function at the discretion of the investigator 4.5. Known structural heart issues at the discretion of the investigator, including but not limited to PFO, VSD and bicuspid AV 4.6. Implanted prosthetic material including but not limited to cochlear implants, orthopaedic implants, implantable cardiac devices, cardiac valves and neurological stimulators 4.7. Recurrent sinusitis 4.8. Previous sinus surgery 4.9. Planned surgical, dental, orthodontic, dental hygienist or pre-operative appointment over the study period 5. General health history (self-reported and or confirmed from GP questionnaire or medical records or summary if deemed necessary). Moderate to severe ill health including but not limited to: 5.1. Asplenia or dysfunction of the spleen 5.2. Chronic respiratory disease (for example asthma on medication, COPD, emphysema, bronchiectasis) 5.3. Chronic heart disease (for example angina, ischaemic heart disease, chronic heart failure). Controlled stable hypertension with or without angina may be included 5.4. Chronic kidney disease (for example nephrotic syndrome, kidney transplant, on dialysis) 5.5. Chronic liver disease (for example cirrhosis, biliary atresia, hepatitis) 5.6. Chronic neurological conditions 5.7. Connective tissue disease 5.8. Dementia 5.9. Diabetes mellitus (including diet controlled) 5.10. Immunosuppression or history of receiving immunosuppressive therapy at the discretion of the investigator 5.11. Individuals with cochlear implants 5.12. Individuals with major cerebrospinal fluid leaks (for example following trauma, major skull surgery or requiring CSF shunt) 5.13. History of a bleeding disorder (for example factor deficiency, coagulopathy or platelet disorder) or prior history of significant bleeding or bruising following IM injections or venepuncture 5.14. Any uncontrolled medical, surgical or mental health conditions at the discretion of the study doctor 5.15. Significant mental health condition (for example previous admissions in a psychiatric unit, at the discretion of the clinician) that would impair the participant’s ability to participate in the study 6. Taking medications 6.1. Any medication that may affect the immune system in the last 3 months (for example systemic steroids PO or IM or IV, Roaccutane, disease-modifying anti-rheumatoid drugs) 6.2. Current or intended long-term or intermittent use of antibiotics over the course of the study 6.3. Recent systemic antibiotic exposure in the last 1 month 6.4. Use of any medication affecting blood clotting (any oral or injectable anticoagulants) except for aspirin for secondary cardiovascular prevention 6.5. Use of any medication or other product (prescription or over-the-counter) for symptoms of rhinitis or nasal congestion within 4 weeks of enrolment 7. Volunteers who are pregnant, lactating or intending on becoming pregnant during the study 8. Volunteers who have close contact with individuals at higher risk of infection 8.1. Children under 5 years of age 8.2. Chronic ill health or immunosuppression (adults or children) 8.3. Older adults aged 65 years or above 8.4. Household close contact with compromised skin barrier function, psoriasis, eczema or other chronic skin condition requiring treatment in the last year 9. Volunteers (including healthcare workers) who have close contact in high-risk occupational settings or with high-risk or vulnerable individuals during the study 10. Smoker 10.1. Current or ex-smoker (regular cigarettes, cigars, e-cigarette, vaping or smoking of recreational drugs) in the last 6 months 10.2. Previous significant smoking history (more than 20 cigarettes per day for 20 years or the equivalent, meaning 20 pack years or above) 11. Suspected or known current hazardous or harmful alcohol or drug use, as per investigators’ discretion 12. Intended overseas travel during the course of the study 13. Any other issue which, in the opinion of the study staff, may: 13.1. Put the participant or their contacts at risk because of participation in the study 13.2. Adversely affect the interpretation of the study results 13.3. Impair the participant’s ability to participate in the study 14. Study staff or a partner or dependent child of study staff 15. Household close contact previously or currently involved in this study, provided they have received challenge 16. Stage 2 exclusion only: enrolment in Stage 1 2026-01-01T00:00:00.000Z 2028-12-31T00:00:00.000Z Staphylococcus aureus nasal colonisation Infections and Infestations This study is a two-stage, unblinded, strain-randomised Controlled Human Infection Model (CHIM). It is multicentre, starting in one location with sequential opening of UK locations as required. It is designed to develop and evaluate a safe method of establishing temporary nasal colonisation with Staphylococcus aureus in healthy adults aged 18 to 55 years. In stage I the aim is to find the best challenge dose of up to two strains of S. aureus in order to achieve colonisation in 50 to 70 percent of volunteers. Up to four strains of S. aureus will be trialled and the continuous reassessment method (CRM) will be used to identify the challenge dose. Up to 48 participants per strain will be enrolled. Participants will be screened up to 6 months in advance of enrolment. Screening will involve written consent, a urine test for pregnancy where appropriate, blood tests to check general markers of health, a physical examination and measurement of vital signs. A medical and medication history will be taken. Next of kin information will be requested and they will be provided with a household contact information sheet. Details will also be taken to allow registration on TOPS (trial over-volunteering prevention service) and to allow reimbursement for time and inconvenience. Once enrolled, participants will undergo a 5 day course of standardised decolonisation therapy (nasal antibiotic ointment and antiseptic hair and body wash) starting about 2 weeks before challenge. Participants will have a decolonisation e-diary to record adherence. They will be reviewed about 4 days before challenge for nose samples, body swabs and blood tests. At challenge they will receive a carefully measured dose of liquid containing the candidate strain by dripping it into the nose. The dose will be determined by the continuous reassessment method, which takes into account the proportion of participants colonised up to that point to ensure the best chance of achieving a colonisation rate in the target range. Participants will be followed up with a daily symptom e-diary for safety reasons. This lasts 28 days with a more intensive phase lasting 7 days. There will be a series of more time-intensive in-person reviews on days 1, 3, 7, 10 and 16 after challenge. These reviews are for safety monitoring as well as blood, nose and body swab sampling to check for immune responses and presence of bacteria. On days without in-person review, participants will take nose samples at home and store them in the freezer using provided equipment. Additional home samples will be requested on day 22 and day 42. There will be a further in-person visit on day 28 for blood, nose and body swab sampling. Participants will then be given a further 5 day course of decolonisation therapy. Two follow up visits by phone or email will occur on day 56 and day 182 for safety review. Up to four strains will be trialled, but only up to two strains will progress to stage II once predefined criteria are met, including an estimated colonisation probability within the target range and no safety concerns. If no strain meets criteria, the study will stop. A formal DSMB safety review will be conducted before progression to stage II. Up to 48 participants will be challenged per strain, with a maximum of 192 for stage I. The purpose of stage II is to assess whether colonisation after one challenge offers any protection against colonisation after a second challenge. A new set of participants will be recruited. Participants will be randomised 1:1 to receive either the first or second strain (at the doses selected in stage I) for their primary challenge. Only participants who become colonised at primary challenge will proceed to rechallenge. Participants will undergo a very similar process to stage I, but the day 56 visit will be in-person and this is when they will receive their second decolonisation. Participants not successfully colonised after primary challenge will have their final contact with the study team at the day 182 phone or email visit. Participants successfully colonised after primary challenge will undergo a second decolonisation starting at day 56. The schedule of visits will then repeat with a pre-challenge visit, rechallenge on day 70, and a more intensive follow up period lasting until 56 days after rechallenge, when they will receive their third decolonisation course. Their final contact will be a phone or email visit at day 182 after rechallenge. Rechallenge will initially use the same strain as at primary challenge. The study team will review data as the study progresses, supported by formal interim analyses of rechallenge colonisation rates. Broadly, once 20 participants have demonstrated protection, the strain used for rechallenge will switch from the same strain used at primary challenge to the other strain in stage II, to assess whether protection applies across strains. If only one strain progresses from stage I to stage II, there will be no randomisation and the same strain will be used for both primary challenge and rechallenge. Participants not colonised at primary challenge will not undergo rechallenge and will be followed up for approximately six months. Up to 192 participants will be enrolled in stage II. Other As part of this study, the University of Oxford will share relevant research data with the Ellison Institute of Technology, Oxford. The data they receive will not include participants names, contact details, NHS number or other direct identifiers. The data will be labelled only with a code. Other ddf94934-7b95-4b75-af83-188db229b789 9726a45e-57e3-492e-90a5-c0322a3db06b 3985d5ec-1cec-4422-a3de-e248965813db ef0990a1-5395-43b0-bec1-9d78db86f4f0 Yes Conor Whelan Public Scientific

Churchill Hospital, Annexe Reception, Centre for Clinical Vaccinology and Tropical Medicine

Oxford United Kingdom OX3 7LE +44 1865611400 conor.whelan@paediatrics.ox.ac.uk Public Andrew Pollard https://orcid.org/0000-0001-7361-719X Principal investigator

Churchill Hospital, Annexe Reception, Centre for Clinical Vaccinology and Tropical Medicine

Oxford United Kingdom OX3 7LE +44 1865611400 andrew.pollard@paediatrics.ox.ac.uk Public University of Oxford University/education https://ror.org/052gg0110 Non-commercial Elliston Institute of Technology http://dx.doi.org/10.13039/501100000272 12055450 true Evaluating the feasibility of a respiratory-swallow training intervention to improve swallow function for people with head and neck cancer ReST-HN This study aims to: 1. Develop a training package for speech and language therapists 2. Train speech and language therapists to use the programme with patients 3. Carry out a study to examine how the training programme would work in practice, using a biofeedback approach 4. Determine whether the project is feasible and likely to be effective within the NHS Background and study aims The problem: In the United Kingdom, 12,200 people are diagnosed with head and neck cancer every year. Difficulties swallowing food and drink following cancer of the head and neck are common. Swallowing difficulties often arise due to the position of the tumour itself (which may be found in the mouth, tongue, voicebox or throat) and after treatment (surgery, chemotherapy and/or radiotherapy). Swallowing difficulties may last a long time and can lead to problems such as fear of eating, losing weight, chest infections, and even death. Swallowing difficulties can also have a negative impact on an individual’s mental health. These difficulties can affect how people interact with others and whether they take part in enjoyable activities. Unfortunately, exercises designed to improve swallowing do not always work for a lot of patients with head and neck cancer. This means we need to look for new ways of improving swallowing. The solution: New training, which aims to change the breathing-swallowing pattern of patients with swallowing difficulties, has been developed in America. It seems to work well and improves swallowing for people with head and neck cancer. However, this training programme requires a lot of equipment and training to work. We plan to simplify this training and use equipment that is easy to use, both for therapists and patients. This will benefit patients because, if it works, it will be available to lots of people and can be used at home. This study aims to: • develop a training package for speech and language therapists and patients. • train speech therapists to use the programme with patients. • to see how the training programme works in practice, using simple, easy to use equipment to help coordinate breathing and swallowing • find out about whether the project is doable, likely to work in the NHS and worth investing in. • ask patients and therapists about what they think of the training and whether it can be improved. Who can participate? You may be able to take part if you: • have been diagnosed with swallowing difficulties (dysphagia) by your speech and language therapist or have had a swallow test. • have completed treatment (surgery, radiotherapy, and/or chemotherapy) for head and neck cancer for the first time. • finished your cancer treatment at least 3 months ago, with treatment given to try to cure the cancer. • are 18 years of age or older. • are able to drink fluids (of any thickness) • are able to hold drink in the mouth and then continue breathing through the nose What does the study involve? On your first appointment We need to check that the study is suitable for you. The researcher will test your: 1. breathing-swallowing pattern. You will be asked to wear special equipment. The equipment will include monitors under your chin and nose and around your chest and stomach . 2. lung range. You will also be asked to blow into a device (called a spirometer) to test the amount of air going in and out of your lungs. 3. swallowing ability. If you have not recently completed a formal examination of your swallow, such as a swallow x-ray (videofluoroscopy) or via a camera passed through the nose (flexible endoscopic evaluation of swallowing (FEES)), you will be asked to complete a FEES test. During the procedure a thin, flexible instrument is passed through your nose. The parts of your throat can then be seen as you swallow liquids and foods. It will take approximately 15-35 minutes depending on whether you need a swallow test. If you need a swallow test this appointment will need to take place at an NHS clinic, otherwise we can see you at home, if you’d prefer. You may be unable to take part in the study if your breathing-swallowing pattern or swallowing ability is within the normal range or you have a severe lung condition. There will be two groups: 1. One group will act as a control (with no training) 2. One group will receive training using equipment (biofeedback) If you are able to take part in the study, a computer will randomly choose whether you will be in one of the swallow training groups or the control group (no swallow training). You have a 50% chance of being in one of the training groups and a 50% chance of being in the control group. We get a computer to do this job because we think this is fairest. There are no people making decisions about which person is in which group. At your second appointment you will fill out some surveys about your swallowing difficulties. At the same appointment your breathing-swallow pattern will be measured. These tests will take about 30 minutes. You will also have an x-ray video of your swallowing (videofluoroscopy). In the examination you will be asked to swallow a range of foods and drinks of different consistencies. Barium will be added to the food and drink so it shows up clearly on the x-ray. The x-ray will take about 15 minutes. Swallow training If you are selected to take part in the swallow training, a speech and language therapist will see you once a week (for up to an hour) for up to 6 weeks. The training will focus on changing the timing of your swallow whilst you drink. If you are selected to train using the equipment you will be asked to wear a respiratory belt around your chest. If you are unable to manage certain drinks or foods the training will be tailored to your needs. These treatment appointments will be videoed so that the research team can monitor whether the training is following the guidelines. The training sessions will take place at an NHS clinic or at your home, depending on your therapist or your preference. After the training is completed, we will be unable to offer you further training in this technique. Will I need to attend any other appointments? You will be invited to attend another two appointments, one week after the training and three months later, even if you are in the control group (no training). Each appointment will last about 45 minutes. The tests completed at your second appointment will be repeated at each follow up appointment. These will include: 1) surveys, 2) measurement of your swallowing (x-ray), and, 3) assessments of your breathing-swallowing pattern. These appointments will take place at an NHS clinic. You may be invited to an interview to talk about what your experience of taking part in the study was like. This might be during training or after training. Interviews will be audio-recorded and will last up to an hour. You can decide whether or not you would like to take part. You will receive £20 and travel for every appointment you attend once you are taking part in the study. What are the possible benefits and risks of participating? The videofluoroscopy (video x-ray of the swallow) generates real-time moving pictures using radiation. We are all exposed to natural background radiation every day in our environments. The x-ray will give you additional radiation on top of your natural background radiation. Your radiation exposure for each videofluoroscopy is small, about the same as 2-7 weeks of natural background radiation, which you normally receive every day. If you need a swallow test using an endoscope (FEES) it is possible that you may experience mild discomfort. You will have had one of these before with your ENT doctor. There is a small chance you might have a nose bleed (1%), however this is very rare. Where is the study run from? The study is run from the University of Liverpool, UK You may be eligible to take part in the study if you live in Merseyside or Cheshire. When is the study starting and how long is it expected to run for? The study is starting in May 2026 and finishing in February 2028 Who is funding the study? The National Institute for Health and Care Research (NIHR) funds this study (303061) Who is the main contact? The chief Investigator is Dr Michelle Lawton, Michelle.Lawton@liverpool.ac.uk Intervention uptake Screening and enrolment logs recording number of eligible patients and number consenting Throughout recruitment period Acceptability of the intervention Semi-structured qualitative interview during and following the intervention Acceptability of randomisation Semi-structured qualitative interview during and following the intervention Completeness of outcome measures assessment completion records calculating percentage completed 3 month follow up Adherence to treatment manual Treatment fidelity checklist scored from video-recorded sessions During intervention period Determinants of implementation and mechanisms of change Semi-structured qualitative interview during and following the intervention Respiratory swallow coordination Respiratory inductance plethysmography, nasal airflow and submental surface electromyography analysed using LabChart software Baseline, post intervention, 3 month follow up Lung volume during swallowing Respiratory inductance plethysmography calibrated to lung volume estimates Baseline, post intervention, 3 month follow up Respiratory swallow pattern respiratory inductance plethysmography and nasal airflow recordings Baseline, post intervention, 3 month follow up Respiratory pause duration during swallowing nasal airflow recordings Baseline, post intervention, 3 month follow up Swallow safety Penetration Aspiration Scale scored from videofluoroscopic swallow study Baseline, post intervention, 3 month follow up Swallow physiology and impairment Modified Barium Swallow Impairment Profile scored from videofluoroscopic swallow study Baseline, post intervention, 3 month follow up Swallow related quality of life MD Anderson Dysphagia Inventory questionnaire Baseline, post intervention, 3 month follow up Functional swallow performance Performance Status Scale for Head and Neck Cancer Baseline, post intervention, 3 month follow up Pulmonary function Spirometry measuring forced expiratory volume in 1 second and forced vital capacity ratio using a digital spirometer Baseline only Health related quality of life specific to head and neck cancer European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck module HN43 Baseline, post intervention, 3 month follow up Ethics approval required London-Camden & Kings Cross REC

2 Redman Place, Stratford

London United Kingdom E20 1JQ 24/LO/0164 10.1186/ISRCTN12055450 335217 CPMS: 61140, NIHR: 303061 335217 61140 303061 Interventional Randomized controlled trial Open (masking not used) Active Single Treatment Not applicable 2028-08-29T00:00:00.000Z United Kingdom England Clatterbridge Cancer Centre

Clatterbridge Hospital Clatterbridge Road

Wirral England CH63 4JY RJR62@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 Mid Cheshire Hospitals NHS Foundation Trust

Leighton Hospital Leighton

Crewe England CW1 4QJ RBT@2.16.840.1.113883.2.1.3.2.4.18.48 false 1. Have a clinical diagnosis of dysphagia on instrumental assessment using videofluoroscopic swallow study or fibreoptic endoscopic evaluation of swallowing 2. Have dysphagia indicated by outcome measures with penetration aspiration scale score at least 3 and/or DIGEST efficiency grade at least 1 3. Have completed chemotherapy, radiotherapy and or surgical intervention with curative intent for first time diagnosis of squamous cell carcinoma of the head and neck at least 3 months previously 4. Be able to give informed consent 5. Be aged 18 years or above 6. Be able to tolerate fluids orally IDDSI Level 0 to 3 7. Exhibit a suboptimal respiratory swallow pattern exhale to inhale, inhale to inhale, or inhale to exhale in at least 20% of swallow trials 8. Be able to hold a drink orally and resume breathing Mixed 18 Years 120 Years All 40 0 1. A nasogastric tube, laryngectomy or tracheostomy where tube presence will alter respiratory swallow coordination 2. Known neurological disease or insult impacting on swallowing 3. Spinal surgery or insult impacting on swallowing 4. Chronic COPD with forced expiratory volume less than 30% on pulmonary function testing 5. Recent history within the last 3 months of aspiration pneumonia 2026-05-06T00:00:00.000Z 2028-02-29T00:00:00.000Z Swallow training in head and neck cancer Cancer Development of Respiratory-Swallow Training programme (biofeedback) A treatment manual will be developed for ReST using biofeedback using the TIDieR framework detailing: the equipment set-up, feedback provision, monitoring and measuring of goals for both interventions. Respiratory Swallow Training (ReST) using biofeedback group: Clinicians (Speech and language therapists) at the participating sites will be trained to deliver ReST using biofeedback, as per the treatment protocol. Training will include: theoretical underpinning, treatment procedure, practical application and use of instrumentation. Competency will be determined by successful (100%) identification of optimal respiratory-swallow coordination (exhale-swallow-exhale pattern) using visual feedback. ReST training sessions with take place up to 1 hour weekly for up to 6 weeks until mastery is reached. An experienced speech and language therapist, who has received training, will deliver ReST using biofeedback to participants at an NHS clinic or the participant’s home, dependent of individual preference or clinical availability. Participants will continue to see their treating therapist as part of usual care (if applicable) whilst receiving ReST. The treatment protocol will follow a tripartite design incorporating principles of motor learning as outlined by Martin-Harris & colleagues (2015). Goals will be included which are divided into sub-goals within three learning domains: 1) identification, 2) acquisition, and 3) mastery. Participants will only move onto the next phase when they have demonstrated 90% accuracy (over 10 trials) on any given goal. 1. Identification: Participants will be presented with a series of static graphical representations of swallowing and respiration via an online programme. These graphics will show the respiratory cycles and the swallowing. Participants will be asked to identify specific targets to demonstrate their ability to recognise: (1) phases of breathing, (2) the swallow trigger, and (3) optimal versus suboptimal swallowing patterns. Participants will then progress to viewing similar representations presented dynamically on a computer screen. To advance to the next stage, participants must correctly identify targets in at least 9 out of 10 trials. If fewer than 9 trials are correctly identified, additional practice will be provided and/or earlier learning objectives will be revisited. This training will be delivered as an online module that can be completed either independently at home or with support from a therapist, according to participant preference. 2. Acquisition: The aim of the acquisition module is for participants to be able to self-initiate swallows during the expiratory cycle. Participants will view a visual graphical representation of their own respiratory-swallow pattern on the computer screen, via respiratory Inductance plethysmography and a manual switch, which will be pressed by the therapist to mark the swallow. The clinician will provide verbal feedback to participants in relation to accuracy. Teaspoons of thin fluids will be initially trialled, providing they can be safely swallowed. If participants are unable to swallow thin fluids safely, thicker fluids will be trialled as per the findings on instrumental swallow assessment. Swallow initiation during expiration will initially be targeted (with and without visually guided feedback). Only consistencies the participant is safely able to tolerate will be used for training (as per the instrumental swallow assessment). Participants will need to successfully complete 9/10 trials at each stage to move on to the mastery phase. 3. Mastery: The aim of the mastery module is to ensure participants are able to use an optimal respiratory swallow pattern (i.e. exhale-swallow-exhale) with 90% consistency, without visual or verbal feedback. The programme will run for 5-6 weeks. Usual care group: Usual care refers to speech and language therapy provided by the treating speech and language therapist as part of routine care. Speech and language therapy (SLT) aims to remediate swallowing, speech and voice difficulties following head and neck cancer. SLT may include assessment (clinician-rated, patient-rated and instrumental), intervention and/or review, which may focus on the use of compensatory strategies, strengthening and range of motion exercises, supporting mood and confidence, working with family/carers and providing information. Therapy is individually tailored and is largely face-to-face, however it may incorporate telehealth or group work. Patients are seen as inpatients, outpatients or in the community. Dysphagia therapy may include but is not limited to: swallow exercises (e.g. effortful swallow, Masako manoeuvre, Mendelsohn manoeuvre, supra-glottic swallow) and non-swallow exercises (e.g. range of movement exercises, tongue strengthening, expiratory muscle strength training). Therapy may also focus on speech and voice training, directly targeting articulation and vocal quality. Other The datasets generated during and/or analysed during the current study will be stored in a publicly available repository (University of Liverpool repository, anonymised raw data will be shared, the data will become available following study completion for a period of 10 years, consent from participants will be obtained) Stored in publicly available repository Protocol

9c0210de-c34c-4430-ba6f-1563bc675a84 108cfc4b-7016-4079-a219-ce0c9bb11e82 9bf64e5e-9517-4e34-aea1-60cd9a583006 Yes Protocol file 49396 Protocol ReST-HN WP3 only 10.04.26 V1.7.pdf b4d7700b-ffa0-43cd-ab7f-380971622c24 true application/pdf 624483 a9665fcb4383342dc4700009dfd4a6ee Michelle Lawton https://orcid.org/0000-0002-2399-6643 Public Scientific Principal investigator

School of Allied Health Professions & Nursing, Institute of Population Health / Liverpool Head and Neck Centre, University of Liverpool, 1.2 Whelan Building, The Quadrangle, Brownlow Hill

Liverpool United Kingdom L69 3GB - michelle.lawton@liverpool.ac.uk Public University of Liverpool Hospital/treatment centre Non-commercial National Institute for Health and Care Research http://dx.doi.org/10.13039/501100000272 16496629 true Impact of menstrual cups on adolescent girls' reproductive health and education IMARA Primary objective: To determine the impact of menstrual cups provided to junior school (JS) girls on pregnancy and school dropout Secondary objectives: 1. To measure the age-specific rates of pregnancy and child marriage in JS girls and identify antecedent risk factors associated with these outcomes 2. To determine the rate, risk factors and reasons for dropout and absenteeism among junior schoolgirls 3. To measure the impact of the menstrual cup on learning via adapted assessments and the Kenya Junior School Education Assessment 4. To determine the impact of menstrual cups on girls' sexual behaviours, including age of sexual début, coerced sex, number and age of partners, condom/contraception use 5. To examine the effect of the menstrual cup on the vaginal microbiome, STIs and BV in a representative sub-study 6. To determine the cost-effectiveness and separately, cost-benefit of the menstrual cup when given to schoolgirls 7. To determine the uptake and safety profile of menstrual cups Background and study aims Adolescent girls are acutely susceptible to sexual and reproductive health (SRH) harms through incomplete biological development, inadequate knowledge of menstruation and puberty, lack of autonomy, social pressures around sex, and harmful gender norms. In many low- and middle-income countries (LMICs), including Kenya, where poverty and gender-based violence are pervasive, girls face sexual abuse, have limited agency to navigate sexual encounters safely, and may resort to transactional sex to obtain daily essentials including menstrual hygiene products. This leaves girls vulnerable to adolescent pregnancy, child marriage, sexually transmitted infections (STIs) and school dropout, with lasting effects across the life course. Trials are needed to test interventions that combine effects that improve girls’ menstrual needs, reduce risky sexual behaviours, and modify social norms. We have conducted prior trials evaluating the impact of menstrual (cups, sanitary pads) and structural (cash transfer) interventions on SRH and school outcomes in about 4750 schoolgirls in rural Kenya. We found menstrual cups were acceptable to parents and to younger and older adolescents, and girls reported improved menstrual hygiene and school engagement and reduced stigma. Cups reduced the incidence of STIs and bacterial vaginosis, suggesting they are a multipurpose tool, improving menstrual care and reducing sexual risks. Our data suggested earlier-aged cup use, e.g., soon after the first menstrual period, may offer the highest protection to maintain a healthy vaginal microbiome. However, our prior trials missed robust measurement and evaluation of the effect of menstrual cups on adolescent pregnancy and on education outcomes such as school dropout, absence, and exam scores. Funding has been provided allowing us to improve our study methods to fully evaluate menstrual cups as a multipurpose tool. Our study aims to evaluate if the provision of menstrual cups will impact educational, sexual and reproductive health and social equity outcomes compared with girls maintaining usual practice in junior schools in western Kenya. Who can participate? The main trial participants are girls attending as day students in junior schools in Siaya County, western Kenya. Girls can participate if they live in the study area, attend the selected junior schools, have parent consent and themselves assent, and have no disability that would preclude them from being able to join the study activities. Our target population are girls in the first year of junior school (grade 7), who would be followed up until they complete junior school (grade 9), e.g., over approximately 2.5 years. What does the study involve? This study includes a menstrual cup group and a control group (where participants are provided the menstrual cup at the end of the study). At the randomisation ceremony head teachers allocate schools to the cup or control group. Informed parent consent through school meetings will first take place before eligible schoolgirls are invited to join and assent. Following participant enrolment, a baseline self-completed survey will be conducted among participants in school, with follow-up surveys conducted every 6 months. A variety of qualitative studies will be conducted among participants agreeing to join activities across the course of the study. Absence will be recorded through software, enabling more accurate recording by teachers. Participants reported to drop out will be visited in their homes to verify this, record pregnancies, and continue biannual surveys to maximise completeness of survey coverage. In a sample of about 10 schools, a sub-study will take place in about 600 girls (300 in the cup group and 300 in the control group). Following parent consent and their assent, participants will be invited to do vaginal swabs, in a private setting, to investigate the vaginal microbiome and to diagnose if they have bacterial vaginosis and/or an STI. Private individual treatment will take place after test rests are obtained. Costings will be conducted throughout to enable the trial data to be used for cost-benefit and cost-effectiveness analysis. In addition to activities among the participants, additional studies will be conducted among a variety of stakeholders to provide contextual information to help understand trial outcomes and to inform policy implications. What are the possible benefits and risks of participating? Girls will receive a menstrual cup, puberty and hygiene education, and training on safe and effective use. The control group will receive a small stationary item at enrolment and a menstrual cup (with training) at the end of the study. Participants are thought likely to benefit from improving their self-esteem and autonomy by contributing to the study. Participants in our previous studies reported enhanced esteem through study participation. The risks for schoolgirls participating in this study include initial embarrassment discussing menstruation with possible shame associated with poor management. This will be mitigated by discussion with the female staff who have worked with adolescent girls for many years. Girls may also feel discomfort when first using the menstrual cup until they are familiar. This will be addressed through training of female experts who will be available to support safe and effective use, with repeat training monthly for 3 months, then quarterly, plus SMS messaging if further support in between training is required. Girls may be triggered by some questions on sexual and reproductive health or behaviours; our female counselling staff will be available, and we have a safeguarding pathway prepared should girls need additional counselling support. Girls in the sub-study investigating STIs and the vaginal microbiome may find the process of swabbing overwhelming; we have trained nurses and female counsellors to assist with every step, and all activities will be conducted in privacy. Treatment of infections is conducted confidentially by our study nurses. Finally, participants are informed from study start and during procedures that they have the right to withdraw at any time with no negative consequences should they so wish. Where is the study run from? Kenyan Medical Research Institute (Kenya) When is the study starting and how long is it expected to run for? May 2026 to February 2029 Who is funding the study? Bill and Melinda Gates Foundation (USA) Who is the main contact? Prof. Penelope Phillips-Howard, penelope.phillips-howard@lstmed.ac.uk The combined incidence of adolescent pregnancy and/or school dropout follow-up surveys 6 monthly intervals and verification house visits over approximately 2.5 years Safety: Incident cases of toxic shock syndrome community surveillance endline, approximately 2.5 years AKIBA Sub-Study: Prevalence of optimal community state type (CST-I, Lactobacillus crispatus dominated) follow-up surveys termly intervals over approximately 2.5 years Incidence of adolescent pregnancy follow-up surveys 6 monthly intervals and verification house visits over approximately 2.5 years Incidence of school dropout follow-up surveys 6 monthly intervals and verification house visits over approximately 2.5 years Incident mental health disorders follow-up surveys using Patient Health Questionnaire-9 (PHQ-9) and EuroQoL 6 monthly intervals over approximately 2.5 years AKIBA Sub-Study: Incidence of bacterial vaginosis (BV) and sexually transmitted infections (STIs) (composite of gonorrhea, chlamydia, trichomoniasis) follow-up surveys annual intervals over approximately 2.5 years Ethics approval required Liverpool School of Tropical Medicine Research and Ethics Committee

Pembroke Place

Liverpool United Kingdom L3 5QA 0136 Scientific and Ethical Review Unit

Mbagathi Way

Nairobi Kenya 54840 5379 10.1186/ISRCTN16496629 Interventional Randomized controlled trial Open (masking not used) Active Parallel Prevention Not applicable 2029-02-28T00:00:00.000Z Kenya Kenya Medical Research Institute

Kisian Campus, Busia Road

Kisumu Kenya 20778 false Schools: 1. Junior day schools in select sub-counties in Siaya County 2. Schools that educate girls or are co-educational 3. Schools receiving approval to participate from the Head Teacher Main trial participants: 1. Girls attending junior schools (JS) 2. Girls who are day students 3. Girls who live in the study area 4. Girls who have parental consent and assented 5. Girls who have no severe disability precluding them from participating Others: Parents: Parents or guardians of girls participating in the trial who consent to participate Boys: Boys in same schools as participating girls, who receive parental consent and assent Teachers: Teachers in study schools who consent to participate Other stakeholders/community members: Persons in the community of the study schools who work with or who have responsibility for or relationships with adolescent girls, e.g., local ministry officials, chiefs, religious leaders, community males who consent to participate Mixed 12 Years 18 Years Female 2070 0 Schools: 1. Boys-only schools 2. Girls’ schools that require boarding 3. Special needs schools Main trial participants: 1. Girls who live outside the study area 2. Girls who attend boarding schools 3. Girls whose parental consent or girl’s assent is refused 4. Girls with a severe disability precluding participation 5. Girls cannot take part if they have an allergy to silicone or if they plan to move from the study area within the next year Others: Parents: Parents in non-study schools or in study schools but whose daughters are not enrolled in the study Boys: Boys in non-study schools or whose parents do not provide consent Teachers: Teachers outside the study schools or who do not consent Other stakeholders/community members: Persons with no knowledge, experience or responsibility for adolescent girls or no knowledge of the local community 2026-09-01T00:00:00.000Z 2026-09-30T00:00:00.000Z Reproductive health and education Other Schools are the unit of randomisation (clusters), and girls the unit of measurement. A census of junior schools in the area will be completed. A computer-generated randomisation list will be produced by the trial statistician at LSTM. Randomization will adjust for school-level characteristics (e.g., school size) to ensure balance across study arms. Schools with head teacher approval will be randomly allocated into two arms using a 1:1 ratio. The actual allocation of schools to study arms will be revealed using community ceremonies with the Head Teachers of the school. Because schools allocated to the ‘usual practice’ will receive menstrual cups at the end, cup allocation may be perceived by communities as an intervention provided ‘immediately’ vs ‘delayed’. Participants will be randomised (through school allocation) to one of two arms: 1. One menstrual cup (CouldYou?®) with education and training materials for safe, effective cup use. 2. ‘Usual practice’ control (control arm), who will receive a stationary item (notebook) at the beginning of the study and the menstrual cup with training on safe use and care at study end. Menstrual cups are medical-grade silicone-based receptacles inserted in the vagina to collect menstrual blood and are safe, cost-effective, and environmentally friendly. There are now over 100 brands of menstrual cups worldwide. Branded menstrual cups have been registered and approved in numerous countries including the United States Food and Drug Administration (US FDA class 2 registration). In the US, menstrual cups are classed as a medical device and in Europe as a hygiene product. In 2022, ISO established a new committee to define standards for menstrual products (https://www.iso.org/committee/8933440.html). This includes ISO for menstrual cups: ISO/TC 338 (https:committee.iso.org/home/tc338). Kenya, Uganda, South Africa, Ghana, Namibia, Eswatini, Sudan and Egypt are participating members in Africa, along with most countries in America, the Middle East, Asia, Europe and Australasia. Kenya is represented by the Kenya Bureau of Standards (KREBS)(https://www.iso.org/member/1854.html). The menstrual cup used in this study (CouldYou?) (https://couldyou.org/period-poverty/) is made from medical-grade silicon and manufactured in a cGMP manufacturing company, which is also ISO 13485 certified; cups are manufactured in ISO 8 clean rooms and are FDA-registered (FDA registration #3018179390). CouldYou? Cups are distributed within Kenya for menstrual cup programmes, although not in the rural area of our study, and have KPPB licence approval (KPPB # PPB/DON/00277/24). Device Phase III Menstrual cup (CouldYou?®) Not expected to be made available Protocol

67e12641-353c-4e96-a762-d78ff6a4255c abe8c819-c179-4bd7-bc72-5768dcb84aa7 f2fb59b3-b478-4630-9f56-b5f06ef0ccc7 No Protocol file 49221_PROTOCOL_V0.9_09Feb26.pdf be235853-6e09-4596-be5d-2ea02d8415cc true application/pdf 1937954 f6d4f07ac26ee8eb6bbff472424cf4a0 Penelope Phillips-Howard https://orcid.org/0000-0003-1018-116X Principal investigator Scientific Public

Department of Clinical Sciences, Pembroke Place

Liverpool United Kingdom L3 5QA +44 (0)7985431005 penelope.phillips-howard@lstmed.ac.uk Public Liverpool School of Tropical Medicine https://ror.org/03svjbs84 Non-commercial Bill and Melinda Gates Foundation http://dx.doi.org/10.13039/100000865 78570937 true Peer-to-peer support for people with head and neck cancer HOPE HNC This project aims to co-develop a prototype HNC peer support intervention for subsequent evaluation by: 1. Exploring patients’ and relatives’/carers’ perspectives on receiving and providing peer support across the patient journey 2. Exploring health and social care professionals’ perspectives on delivery of peer support 3. Synthesising this information, and co-creating a peer support intervention, for future testing Background and study aims We aim to improve support services for people diagnosed with head and neck cancer (HNC). The number of people treated for HNC is increasing. About a third have anxiety or depression (also known as emotional distress) which is bad enough to require professional support. Emotional distress reduces quality of life and can make living with symptoms of HNC worse. Many have long-term and complex difficulties with altered appearance, speaking, eating, and drinking difficulties, leaving them very isolated. Some people with HNC do not wish to engage with professional services to help reduce emotional distress. A wider range of care and support must be available. Peer support is one option; it involves people with a similar condition providing social, emotional, or practical support to others. This form of support has been beneficial in other cancer groups. Peer support could improve mental health, provide access to help closer to home and reduce healthcare use. Little is known about the best way to set up a peer support service. Multiple perspectives are required including HNC patients, local and national healthcare providers, social care providers, and cancer charities. Developing a better understanding of how to design and organise a peer support service is the primary aim of this project Who can participate? 1. Head and neck cancer patients aged 18 years and over 2. Carers and relatives of head and neck cancer patients 3. Health and social care providers who are working in the NHS in HNC care provision What does the study involve? There are three interlinked studies. Study 1. Interviews with HNC patients and carers/relatives of people with HNC. These interviews will focus on people's experience, knowledge and ideas about peer support. Study 2. Interviews with health and social care providers who work with people with HNC. Interviews will focus on their experience, knowledge and attitudes about peer-to-peer support. Study 3. A series of three workshops involving patients, carers/relatives, and health and social care professionals to bring together the information obtained in studies 1 and 2 to develop a peer-to-peer support service that could be evaluated in future research. What are the possible benefits and risks of participating? We do not anticipate any major risks. It is possible that people may become upset when talking about your experiences. The researcher can direct you to further support and help if you need it. We hope this study will benefit future patients, health and social care professionals involved in peer support services. We cannot promise that anyone participating will benefit directly, but many people find that taking part in studies like this is useful because they can air their views and reflect on things. Where is the study run from? Institute of Population Health, University of Liverpool (UK) When is the study starting and how long is is it expected to run for? October 2025 to September 2026 Who is funding the study? National Institute for Health and Care Research (NIHR) (UK) Who is the main contact? Dr Peter Fisher; plfisher@liverpool.ac.uk A model of a peer-to-peer support service a qualitative synthesis the completion of the series of interlinked studies Ethics approval required West of Scotland REC 3

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

Glasgow United Kingdom G12 0XH 25/WS/0129 10.1186/ISRCTN78570937 Observational Qualitative research; cross sectional study 2026-09-30T00:00:00.000Z United Kingdom England Mersey Care NHS Trust at Aintree Hospital

C/o University Hospital Aintree Fazakerley Hospital Lower Lane

Liverpool England L9 7AL University of Liverpool

Institute of Population Health University of Liverpool Waterhouse Building, Block B Brownlow Street Liverpool United Kingdom

Liverpool England L69 3GF true HNC patients: 1. HNC patients who are considered medically stable by their clinical care team 2. Aged at least 18 years old 3. Have a sufficient written and spoken English to be able to participate in interviews, workshops and provide informed consent Relatives/carers of HNC patients: 1. Have supported an individual through a diagnosis of HNC and associated treatment 2. Aged at least 18 years old 3. Have sufficient written and spoken English to be able to participate in interviews, workshops and provide informed consent Healthcare and social care providers: 1. Involved in HNC care provision 2. Aged at least 18 years old Mixed 18 Years 99 Years All 70 0 Patients: 1. Do not have capacity to provide informed consent Relatives/carers: 2. Do not have capacity to provide informed consent 3. Carers themselves who have a diagnosis of HNC Healthcare and social care providers: 4. Are not involved in HNC care provision 2025-10-15T00:00:00.000Z 2026-09-30T00:00:00.000Z Head and neck cancer Cancer This 16-month qualitative study has three interlinked studies, each of which contributes to the overall aim of developing a peer-to-peer support model. Study 1: patient and relatives'/carers' perspectives of peer-to-peer support We aim to recruit approximately 20 patients and 10 relatives/carers. Participants will be recruited via local NHS Trusts, existing Patient Research Forum contacts, and social media, e.g., local and national HNC charities and support groups. Participants will be interviewed about their experiences and views of peer-to-peer support. Interviews will last for approximately 45 minutes. Participants will be offered the option of remote (e.g., video calls, telephone calls or in-person interviews) at their preferred location depending upon their personal requirements. Study 2: healthcare and social care providers' perspectives of peer-to-peer support. We aim to recruit approximately 20 health and social care providers who will be recruited through adverts and an email sent by the PI at the study site, publicity campaigns, adverts through professional websites and forums, social media and newsletters. The Postdoctoral Research Associate (PRDA) contact details will be provided on all materials. Potential participants will be sent a participant information leaflet via post/email. Interviews with staff will be conducted either face-to-face or over the telephone/teleconference. Participants will be interviewed about their experiences and views of peer-to-peer support. Study 3: co-production workshops to develop the model of a peer-to-peer support intervention. Patients and family members, health and social care professionals who participated in the interviews, and advisory group members will be invited to participate in the co-design workshops. We aim to recruit approximately 30 participants. A series of three 3-4-hour workshops adapting the format and delivery for underserved HNC patient groups (e.g., those with speech difficulties) will be conducted. Feedback from the project management group and PPI group will inform the delivery and frequency of these workshops, which will remain flexible to need. Participatory methods will be used to empower and promote consensus-building for developing the prototype. Over the course of the three workshops, participants will consider the nature of peer support, what does good peer-to-peer support look like and how a peer support service might operate within the head and neck cancer treatment pathway Participants will begin to develop potential content and to consider ‘what does good peer-to-peer practice look like?’ and 'the group will be supported to develop the intervention, engaging with the potential solution(s) and corresponding materials (considering outputs/evaluation, timing and presentation of service, outcome measures, implementation mechanisms, and their flexibility according to context).    Workshop 3: The group will examine the prototype solution, the need for any adaptations and provide final feedback. By the end of study 3, full consideration will be given to the potential barriers and facilitators to implementing the service and any corresponding materials. Other Not expected to be made available 619f8b8e-ecec-403a-8d83-63394dc6b619 d2cb698a-d8ff-4a4d-b810-5e9beddeb893 9b823c35-184d-4bf8-908c-11ae9070571a No Peter Fisher https://orcid.org/0000-0002-7388-720X Public Principal investigator Scientific

Department of Primary Care and Mental Health Institute of Population Health Eleanor Rathbone Building

Liverpool United Kingdom L69 7ZA +44 (0)1517944160 peter.fisher@liverpool.ac.uk Public University of Liverpool https://ror.org/04xs57h96 Non-commercial National Institute for Health and Care Research http://dx.doi.org/10.13039/501100000272 55288596 true A three-arm randomised feasibility trial of birth options interventions to predict, inform and offer choices to reduce emergency caesarean birth in first pregnancies Aim: To establish if it is possible to implement the Birth Options Interventions and recruit and retain participants in the Birth Options feasibility trial Objectives: 1. What is the recruitment rate to the Birth Options Feasibility Trial? 2. What proportion of women and birthing people complete follow up? 3. Is the Birth Options intervention acceptable to families and clinical staff? 4. What are the reasons for participation/non-participation in the study? 5. How can recruitment to a main trial be optimised? 6. What proportion of women opt for each birth option? 7. Is it feasible to collect the proposed outcome measures for a follow-on trial to evaluate clinical and cost-effectiveness. 8. Exploratory analysis of the proposed outcome measures and characteristics associated with choice of option. 9. What do participants think of the intervention and are any refinements needed? Background and study aims Many women in England have caesarean births – about 42% of all births, and more than half of these are emergency operations. Emergency caesareans can sometimes lead to birth trauma. Women say they want clearer information to help them make choices about how they give birth. This study looks at whether it is possible to run a larger trial comparing three approaches: usual care, a guided conversation about birth options, and a guided conversation plus a tool that predicts the chance of needing an emergency caesarean. In the long term, the study aims to see if these approaches affect how satisfied women feel with their choices and whether emergency caesareans become less common. Who can participate? Women who are between 28 and 37 weeks pregnant with their first ongoing pregnancy are invited to take part. What does the study involve? Participants fill in a questionnaire between 28 and 36+6 weeks of pregnancy. They are then randomly placed into one of three groups: 1. Usual care 2. A guided conversation about birth options 3. A guided conversation plus a prediction tool for emergency caesarean The conversation takes place at around 36 weeks. After that, participants can choose vaginal birth, induction, or planned caesarean. The study team collects feedback from participants and their midwives or doctors, and gathers information about pregnancy and birth. Participants also complete short questionnaires about mental health and birth expectations after the conversation, and about experience and mental health at 6 weeks and 6 months after the baby is born. What are the possible benefits and risks of participating? Taking part may help participants feel more informed and confident about their birth choices. The study could also improve care for future mothers. There are no major risks from taking part, but the conversations and questionnaires may take some time and could feel sensitive for some people. Where is the study run from? University of Liverpool (UK) When is the study starting and how long is it expected to run for? January 2026 to September 2027 Who is funding the study? National Institute for Health and Care Research (NIHR) (UK) Who is the main contact? Dr Abi Merriel, BirthOptions@liverpool.ac.uk Feasibility of recruitment: do we recruit to time and target, the number of patients recruited to the study the end of the recruitment period 1. Recruitment rate to the Birth Options Feasibility Trial: number of recruits per month reported at study close 2. Completion of follow-up to the Birth Options Feasibility Trial: number of women completing the study at study close 3. Acceptability of Birth Options intervention to families and clinical staff: examined using surveys post intervention and qualitative interviews post intervention 4. Reasons for non-participation/non-participation: examined using qualitative interviews at the point of declining to participate 5. Optimisation strategies for recruitment to a main trial: identified via qualitative interviews at the time of decline, drop out, completion and with study staff at the end of the trial 6. Proportion of women opting for each birth option recorded after consultation 7. How complete was the collection of proposed outcome measures: number of surveys completed, completeness of case report form at end of study follow-up. 8. Exploratory analysis of the proposed outcome measures and characteristics associated with choice of option: demographic, clinical and experience outcomes reported by intended and actual mode of birth at 6 weeks and 6 months postnatally. 9. What was the feedback on the intervention and suggested refinements: collected via qualitative interviews following intervention and post birth for women and at the end of recruitment for staff. Old ethics approval format Approved 27/11/2025, South East Scotland Research Ethics Committee 01 (Headquarters, Mainpoint, 102 West Port, Edinburgh EH3 9DN, UK; Tel: not applicable; Sandra.Wyllie@nhs.scot), ref: 25/SS/0100 10.1186/ISRCTN55288596 345836 CPMS: 70096, NIHR: 302530 345836 70096 302530 Randomised cohort study Interventional Randomised controlled trial Treatment 2027-09-30T00:00:00.000Z United Kingdom England Liverpool Women's Hospital

Liverpool Womens Hospital Crown Street

Liverpool England L8 7SS REMAX@2.16.840.1.113883.2.1.3.2.4.18.48 Patient false Women participating in the trial: 1. From 28+0 weeks – 36+6 completed weeks of pregnancy 2. In first ongoing pregnancy past 22+0 weeks 3. Singleton pregnancy 4. 16 years or older Staff/clinicians delivering the intervention: 1. Clinical (Doctors and Midwives) staff delivering study intervention or recruiting to the study Staff recruiting to the study: 1. Research or clinical staff recruiting to the study Mixed 16 Years 99 Years Female 180 0 Women participating in the trial: 1. Having a pre-existing plan for planned caesarean 2. Having a clinical indication that would likely necessitate a planned caesarean, e.g., placenta praevia/accreta 3. Multiple pregnancies 4. Less than 16 years old 5. Not in first ongoing pregnancy Staff/clinicians delivering the intervention: 1. No active participation in the study Staff recruiting to the study: 1. No active participation in the study 2026-02-01T00:00:00.000Z 2027-03-31T00:00:00.000Z Birth options Pregnancy and Childbirth There are three parts to this study: 1. Randomised feasibility trial 2. Intervention development 3. Alongside recruitment intervention 1. Randomised feasibility trial: 180 women will be recruited across three sites and randomised into either: usual care, clinical conversation or prediction of emergency caesarean plus clinical conversation. All women will be asked to complete a baseline questionnaire, a questionnaire around 35-37 weeks of pregnancy, a questionnaire at 6 weeks and then 6 months postnatally. Women in the clinical conversation group will be invited in for a clinical conversation and offer of birth options between 35 and 37 weeks. Women in the prediction + clinical conversation group will either attend for the prediction results and clinical conversation as per above OR attend for an ultrasound scan if they have not already had one in the study window alongside (ideally at the same attendance)the clinical conversation or will attend a further appointment for a clinical conversation with the prediction model if it cannot be facilitated on the same day. Baseline demographics and outcome data will be collected by the site teams. 2. Intervention development: This will be for the clinical conversation (60 participants) and clinical conversation + prediction arms (60 participants). After the intervention women will be asked to complete a questionnaire to feedback on the intervention. We will invite 20 women to an interview after the intervention to feedback on it and 20 women to an interview postnatally to feedback in the context of their birth experience. Alongside this we will ask staff providing the intervention to complete a fidelity questionnaire for each clinical conversation. We will also hold a focus group with staff at each site about the intervention and how to refine it. 3. Alongside recruitment intervention This is used to try to optimise recruitment processes for a main trial. We will record recruitment conversations at each site and analyse these to try to identify elements of successful recruitment conversations. Verbal consent will be sought for this. We will interview upto 20 women who decline participation, 20 who drop out and 20 who complete the study. We will also use the post intervention questionnaires and interviews (mentioned in fidelity section) to understand views on participation/recruitment. We will also interview recruiting staff and map the study flow at participating sites Other Not provided at time of registration Other 8ab41902-786d-422a-9204-5ba5e4b4b5c6 722a3e70-c874-4ff3-9198-a002806de9e2 1667a614-18ca-4ac3-9239-a720ce04590d Yes Abi Merriel Public Scientific Principal investigator

Department of Women’s and Children’s Health, University of Liverpool, First Floor Liverpool Women’s Hospital, Crown Street

Liverpool United Kingdom L8 7SS +44 (0)7801259569 BirthOptions@liverpool.ac.uk Public University of Liverpool Hospital/treatment centre https://ror.org/04xs57h96 Non-commercial National Institute for Health and Care Research http://dx.doi.org/10.13039/501100000272 16400955 true Cognitive brain rehabilitation using transcranial magnetic stimulation in patients with low grade glioma: a proof-of-concept study CARE-LGG 1. Evaluate the long-term cognitive deficits in patients with LGG 2. Identify clinical predictors of cognitive deficits in LGG 3. Establish the utility of remote cognitive testing in patients with brain tumours 4. Generate a spatial map of cognitive deficits in LGG 5. Determine whether rTMS induces any cognitive changes in patients with LGG 6. Determine if any network level changes occur with any cognitive changes induced by rTMS Background and study aims Many people who are treated for a low-grade glioma (a slow-growing type of brain tumour) experience long-term difficulties with memory, concentration, attention, and thinking skills. These problems can affect everyday life, including work, relationships, and independence, and there are currently very limited treatments available to improve them. The aim of this study is to better understand the type and severity of cognitive (thinking) difficulties experienced by people with low-grade glioma and to find out whether a non-invasive brain stimulation treatment called repetitive transcranial magnetic stimulation (rTMS) can help improve cognitive function. Who can participate? Adults aged 18 years or over who were treated surgically for a low-grade glioma at The Walton Centre NHS Foundation Trust from 2013 onwards may be invited to take part. Participation is entirely voluntary, and people can choose which parts of the study they wish to take part in. What does the study involve? The study has three parts. In the first part, participants will be asked to complete online questionnaires and computer-based thinking tests at home, which take less than 90 minutes in total and can be completed with breaks. In the second part, researchers will use results from these tests together with existing MRI brain scans to understand how tumour location relates to thinking difficulties. In the third part, a smaller number of participants with cognitive difficulties may be invited to take part in a proof-of-concept study involving several sessions of rTMS over 4 weeks, along with thinking tests and MRI scans over a three-month period. What are the possible benefits and risks of participating? Taking part may help participants better understand their own cognitive strengths and difficulties. Some participants who receive rTMS may experience improvements in thinking skills, although this cannot be guaranteed. The risks of taking part are overall low. Online assessments may cause temporary tiredness or frustration. rTMS can cause short-lived side effects such as headache, scalp discomfort, or mild fatigue. Serious side effects, such as seizures, are very rare and safety procedures are in place. Where is the study run from? The study is run by the University of Liverpool in collaboration with The Walton Centre NHS Foundation Trust in Liverpool. Some parts of the study are completed entirely online at home, while in-person visits take place at the Walton Centre or nearby research facilities. When is the study starting and how long will it run for? The study is planned to start in February 2026 and is expected to run until August 2030. Who is funding the study? The study is funded by the National Institute for Health and Care Research (NIHR). Additional support, such as some equipment, is provided by industry partners. Who is the main contact? Mr Ahmad Ali, wcft.carelgg-study@nhs.net Subjective cognition Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) 0, 1, and 3 months Objective cognition the Cambridge Neuropsychological Test Automated Battery (CANTAB) battery of electronic cognitive tests 0, 1, and 3 months Objective cognition Hopkins Verbal Learning Test-Revised (HVLT-R), Trail Making Test (TMT), Controlled Oral Word Association (COWA) paper-based tests 0, 1, and 3 months Ethics approval required

10.1186/ISRCTN16400955 345620 CPMS: 63415 345620 63415 Interventional Randomized controlled trial Open (masking not used) Historical Parallel Device feasibility Treatment Not applicable 2030-08-31T00:00:00.000Z United Kingdom England The Walton Centre NHS Foundation Trust

Lower Lane Fazakerley

Liverpool England L9 7LJ RET20@2.16.840.1.113883.2.1.3.2.4.18.48 false WP - Work Package For WP1: 1. Treated for low-grade glioma (grade 2 intrinsic glial tumour) from 2013 onwards at the Walton Centre NHS Foundation Trust 2. Adult patients (>18 years) at time of treatment For WP2: 1. Completed online assessments in WP1 2. Available post-operative volume MRI (T1 or FLAIR) For WP3: 1. Cognitive eligibility: Presence of objective or subjective cognitive deficits defined as >1 SD below the average on any CANTAB test or scoring <55/72 in the Perceived Cognitive Impairments subscale of FACT-Cog 2. Medical stability: no documented change to medical management (chemotherapy, radiotherapy, or surgery) within the last 3 months 3. The invited patients will be selected based on pairwise randomisation from patients who completed assessments in WP1. Pairwise randomisation will be used to balance the two groups on key predictor variables Mixed 18 Years 100 Years All 52 0 For WP1: 1. No explicit exclusion criteria For WP2: 1. No explicit exclusion criteria For WP3: 1. Contraindications to strong magnetic fields (applicable to the TMS sessions and the MRI follow-up scans) 2. Active known pregnancy 3. Unable or unwilling to travel to the Sid Watkins building for TMS sessions 4. History of uncontrolled seizures 2026-02-01T00:00:00.000Z 2027-12-01T00:00:00.000Z Cognitive deficits in patients previously treated for low grade glioma Mental and Behavioural Disorders Only WP3 will be interventional for this study. This will involve 12 sessions of repetitive Transcranial Magnetic Stimulation (rTMS) over 4 weeks. Intermittent Theta Burst dual-target rTMS will be delivered to frontal and parietal targets in the hemisphere contralateral to the treated tumour. The control arm will receive no rTMS. They will only perform the cognitive and MRI assessments to allow comparison. Patients will be allocated to either arm using pairwise randomisation. Device Phase II Transcranial Magnetic Stimulation Not expected to be made available e8d72b23-97e6-4294-80a3-1f6d1872d535 2e68afb1-c00d-4280-962f-1cae7b079f53 30b98956-153f-439c-98a8-926832669150 cd619eca-e2e8-4dc9-aa8b-31ac214daf07 No Ahmad Ali Public Scientific Principal investigator

The Walton Centre NHS Foundation Trust Lower Lane

Liverpool United Kingdom L97LJ +44 (0)151 525 3611 wcft.carelgg-study@nhs.net Public University of Liverpool https://ror.org/04xs57h96 Non-commercial National Institute for Health and Care Research http://dx.doi.org/10.13039/501100000272 Nexstim