REFUEL-MS: Clinical and Cost-Effectiveness RCT
| ISRCTN | ISRCTN82686286 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN82686286 |
| IRAS number | 350492 |
| Secondary identifying numbers | NIHR203290, CPMS 67673, CI/2025/0011GB |
- Submission date
- 09/04/2025
- Registration date
- 20/06/2025
- Last edited
- 17/07/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Nervous System Diseases
Plain English summary of protocol
Background and study aims
Although 9/10 people living with MS report fatigue as a symptom, fewer than a third have been offered any treatment for fatigue as part of their routine care. Of these people, only 9% were offered behavioural treatments. Our overall research programme aimed to work with people with MS to create a digital intervention to help reduce fatigue and then to test how well this intervention – called REFUEL-MS – works in real life. REFUEL-MS is an app that includes physical activity, balance exercises, and cognitive behavioural therapy (CBT) techniques. These were included because previous research has found that they are all effective at reducing MS fatigue. This current study aims to test how well the REFUEL-MS app is at reducing MS-related fatigue compared to usual care and to make sure it is safe for patients.
REFUEL-MS is a patient-led app that people with MS can access on a smartphone or tablet. Patient-led means there are opportunities for patients to choose the content that is most relevant to them (cognitive behavioural therapy, physical activity, or balance exercises), set personal goals, and track progress. The intervention also includes support from a REFUEL-MS healthcare professional through regular virtual appointments and app-based messages. The REFUEL-MS app is not intended to replace the existing MS medical care of participants.
Who can participate?
People living with MS can take part if they:
1. Are aged 18 years and over
2. Have a confirmed diagnosis of MS
3. Are able to read and communicate in English
4. Are a resident of England, Wales or Scotland
5. Are able to see and use a smartphone or tablet
6. Experience fatigue
We are particularly interested in involving participants who are not currently well represented in MS research. This includes those who are older, male, LGBTQ+, from minoritised ethnic backgrounds, live with progressive types of MS, varying levels of disability, lower digital literacy, and lower socioeconomic status. REFUEL-MS is designed to be suitable for individuals with different needs. Participants who do not have a suitable device can be loaned one for the duration of the trial.
We will be recruiting 378 people with MS from the UK MS Register, Guy’s and St Thomas’ NHS Foundation Trust, and community groups.
What does the study involve?
Participants who are eligible and consent will complete an online questionnaire. Participants will then be randomly assigned to one of two groups. One group will get access to the REFUEL-MS programme via the app and the other group will continue their usual care. For both groups, the study will last for 16 weeks.
All participants will be asked to complete online questionnaires about their fatigue, physical activity, mood and quality of life at 4, 6 and 12 months after starting the study. All participants will also receive a monthly phone call from the research team to check how they are doing and if anything unexpected has happened since the last call. Some participants will also be invited to take part in an interview about their experience of using REFUEL-MS.
What are the possible benefits and risks of taking part?
Taking part in this study could improve treatments for MS-related fatigue and support future research. The risks are small, as REFUEL-MS can be used from home and tailored to suit individual needs.
Participant safety is very important to us and the research team will regularly contact participants to check if it is suitable for them to continue in the study. We also understand that MS can come with challenges like anxiety and depression, so along with monthly check-in calls, we will provide information on additional support in the Participant Information Sheet.
We know that completing questionnaires can be time-consuming so we are offering participants a £5 voucher when they complete the questionnaires at 6 and 12 months.
Where is the study run from?
King’s College London (UK)
When is the study starting and how long is it expected to run for?
March 2025 to February 2027
Who is funding the study?
1. National Institute for Health and Care Research (NIHR) (UK)
2. MS Society (UK)
Who is the main contact?
Professor Rona Moss-Morris or Harriet Mortimer, refuel-ms@kcl.ac.uk
Contact information
Scientific, Principal Investigator
King's College London
London
SE1 9RT
United Kingdom
| Phone | +44 (0)207 848 8888 |
|---|---|
| rona.moss-morris@kcl.ac.uk |
Public
King's College London
London
SE1 9RT
United Kingdom
| Phone | +44 (0)207 848 8888 |
|---|---|
| harriet.mortimer@kcl.ac.uk |
Study information
| Study design | Randomized controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Community, Home, Internet/virtual |
| Study type | Quality of life, Treatment, Safety, Efficacy |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet. |
| Scientific title | REFUEL-MS: A two-arm parallel group randomised controlled trial of the clinical and cost-effectiveness of a digital CBT, balance and exercise intervention (REFUEL-MS) for treating fatigue in multiple sclerosis (MS) |
| Study acronym | REFUEL-MS |
| Study objectives | We hypothesise that REFUEL-MS, a blended digital self-management treatment for fatigue in MS, will be more (clinically and cost) effective than Treatment-As-Usual (TAU) at reducing fatigue severity in people with MS experiencing high levels of fatigue. |
| Ethics approval(s) |
Approved 16/07/2025, London - Stanmore Research Ethics Committee (Meeting held by video-conference via Zoom, London, N/A, United Kingdom; +44 (0)2071048208; stanmore.rec@hra.nhs.uk), ref: 25/LO/0256 |
| Health condition(s) or problem(s) studied | Multiple sclerosis |
| Intervention | This study will involve randomising participants to one of two groups (1:1), to compare the REFUEL-MS app, a digital, healthcare professional (HCP) supported self-management treatment for MS-related fatigue, with usual care (treatment-as-usual; TAU) for a period of 16 weeks. Participants in the two groups will complete assessments of fatigue (primary), physical activity, mood, and quality of life at 4, 6, and 12 months. In addition, a qualitative interview study will be conducted with a diverse sample of pwMS who trialed REFUEL-MS and the HCPs supporting the intervention. This should inform our understanding of the factors impacting engagement with REFUEL-MS, perceptions of its effectiveness and potential implementation in routine MS care. Participant Selection: The target total sample size of 378 (189 randomly allocated per arm) people living with MS (pwMS) who meet the eligibility criteria will be recruited through the NHS and the UK MS Register (UKMSR). To address the lack of representativeness of previous trials of fatigue interventions, we also aim to recruit a percentage of people from minoritised or traditionally underserved groups. If we are unable to recruit sufficient people from these groups through the UKMSR and NHS, we aim to recruit through targeted community groups. |
| Intervention type | Device |
| Pharmaceutical study type(s) | Not Applicable |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Refuel MS |
| Primary outcome measure | Fatigue severity measured by the Chalder Fatigue Questionnaire (CFQ) at 6-months post-randomisation |
| Secondary outcome measures | 1. Fatigue impact measured by the Fatigue Severity Scale (FSS) that captures the impact of fatigue on daily functioning at 4, 6 and 12 months post-randomisation 2. Clinically meaningful improvement in fatigue severity, defined as a reduction of >2.3 points from baseline in the total CFQ score, consistent with estimates of the minimum clinically important difference (binary outcome) at 4 and 12 months post-randomisation 3. Clinically meaningful improvement in fatigue impact, defined as a reduction of ≥0.45 points from baseline in the mean FSS score (binary outcome) 4. Depression severity using the Patient Health Questionnaire (PHQ-9) at 4, 6 and 12 months post-randomisation 5. Anxiety severity using the Generalised Anxiety Disorder scale (GAD-7) at 4, 6 and 12 months post-randomisation 6. General quality of life captured by the EQ-5D-5L at 4, 6 and 12 months post-randomisation 7. MS-specific quality of life captured by the MSIS v29 at 4, 6 and 12 months post-randomisation 8. Health and social care utilisation using a Modified Adult Service Use Schedule (ADSUS) at 6- and 12-month post-randomisation 9. Safety, assessed through collection of Adverse Events and Serious Adverse Events throughout the trial (monthly until 6 months then again at 12 months post-randomisation) |
| Overall study start date | 13/03/2025 |
| Completion date | 01/02/2027 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 99 Years |
| Sex | Both |
| Target number of participants | 378 |
| Key inclusion criteria | People living with MS will be eligible if they: 1. Are 18 years of age and over 2. Able to read and communicate in English 3. Are a resident in England, Wales or Scotland 4. Have a confirmed diagnosis of MS 5. Have sufficient vision and manual abilities to use a smartphone or tablet 6. Experience clinical levels of fatigue, scoring ≥4 on the Chalder Fatigue Questionnaire (CFQ), when using bimodal scoring |
| Key exclusion criteria | Potential participants will be excluded if they: 1. Currently undertaking another behavioural or exercise/balance fatigue management programme, other behavioural treatments* 2. Have started on a new disease-modifying treatment for their MS within the last 6 months** 3. Have started a new antidepressant or fatigue medication within the past 3 months** 4. Are currently experiencing severe mental health problems, including psychosis, bipolar disorder or active thoughts of self-harm that are not being appropriately managed, assessed by self-report 5. Score of 11 or under out of 15 on the Mini Montreal Cognitive Assessment, which denotes moderate or severe cognitive impairment (MoCA) 6. Are unable to give informed consent (for example, due to reduced mental capacity) *These participants will have the option of being recontacted by the trial team once they have completed their current treatment to be rescreened for entry into the trial. **These participants will have the option of being recontacted by the trial team once they have been on their treatment for sufficient time to be rescreened for entry into the trial. Please note, participants will only be recontacted up until the end of the recruitment period (likely October 2025), as this is the last possible timepoint for enrolment on the trial in order to complete 12-month data collection. |
| Date of first enrolment | 21/07/2025 |
| Date of final enrolment | 01/02/2026 |
Locations
Countries of recruitment
- England
- Scotland
- United Kingdom
- Wales
Study participating centres
Great Maze Pond
London
SE1 9RT
United Kingdom
Bermondsey Wing
Guy's Campus
Great Maze Pond
London
SE1 9RT
United Kingdom
Sponsor information
University/education
8th Floor Melbourne House
44-46 Aldwych
London
WC2B 4LL
England
United Kingdom
| Phone | +44 (0)20 7848 7306 |
|---|---|
| vpri@kcl.ac.uk | |
| Website | http://www.kcl.ac.uk/index.aspx |
"ROR" |
https://ror.org/0220mzb33 |
Hospital/treatment centre
R&D Department
16th Floor
Tower Wing
Great Maze Pond
London
SE1 9RT
England
United Kingdom
| Phone | +44 (0)2071887188 |
|---|---|
| R&D@gstt.nhs.uk | |
| Website | http://www.guysandstthomas.nhs.uk/Home.aspx |
|
"ROR" |
https://ror.org/00j161312 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
Private sector organisation / Associations and societies (private and public)
- Alternative name(s)
- Multiple Sclerosis Society of Great Britain and Northern Ireland, The MS Society, MS Society UK, Multiple Sclerosis Society UK, MS Society
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 01/06/2027 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | We plan on publishing our trial registration and a paper on our protocol. These will follow our REFUEL-MS dissemination policy, which focuses on open access and publication in peer-reviewed journals. |
| IPD sharing plan | Data-sharing statement to be made available at a later date. |
Editorial Notes
17/07/2025: The following changes were made to the trial record:
1. The ethics approval was added.
2. The date of first enrolment was changed from 01/07/2025 to 21/07/2025.
09/04/2025: Study's existence confirmed by the MHRA.
