HMB to improve functional status in people with liver cirrhosis
| ISRCTN | ISRCTN99030459 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN99030459 |
| IRAS number | 1010060 |
| Secondary identifying numbers | 23HEP856 |
- Submission date
- 25/01/2025
- Registration date
- 08/05/2025
- Last edited
- 09/05/2025
- Recruitment status
- Not yet recruiting
- Overall study status
- Ongoing
- Condition category
- Digestive System
Plain English Summary
Background and study aims
Cirrhosis is liver scarring, caused mainly by alcohol or fatty liver in the UK. People with cirrhosis have poorer quality of life than healthy people. As cirrhosis worsens, they develop more symptoms and require hospital admissions. Cirrhosis causes over 75,000 admissions and costs the NHS £17 billion annually. A leaky gut, due to the breakdown of the gut lining, drives liver damage in cirrhosis. Changes in gut bacteria mean there are fewer bacteria that can break down fibre into short-chain fatty acids (SCFAs). SCFAs are important for the proper function of cells lining the gut. Without them the gut becomes leaky, letting parts of bacteria into the bloodstream leading directly to the liver. This triggers liver inflammation and scar formation. There are no treatments for liver scarring or leaky gut. Increasing gut SCFAs may be effective in treating cirrhosis by restoring the gut lining. HMB, a naturally occurring substance that is already available as a dietary supplement to increase muscle strength, also increases SCFA levels in the gut. In small test trials, HMB was safe and had only minor side effects in people with cirrhosis. We will conduct a trial of HMB compared to a dummy treatment (placebo) in 124 patients with cirrhosis from four hospital outpatient clinics in England.
Who can participate?
Patients aged 18 to 85 years with cirrhosis
What does the study involve?
Patients will be randomly allocated to HMB or placebo twice daily for 12 weeks and followed up for another 12 weeks. At the start and during the trial we will measure the Liver Frailty Index, a combination of strength and function tests, and measures of liver disease, quality of life and mental wellbeing. The researchers will consider the treatment effective if there is meaningful improvement in the Liver Frailty Index after 12 weeks of HMB compared to placebo.
What are the possible benefits and risks of participating?
If the study shows HMB is effective, the researchers will work with national societies and healthcare professionals to encourage the regular use of HMB in routine patient care without delay as it is cheap and widely available. If participants are allocated to the HMB group they might experience an improvement in their physical wellbeing, but they might not. If they are in the placebo group or do not benefit directly, their participation will help us learn more about HMB as a treatment for liver cirrhosis. In this way, participation may benefit people with advanced cirrhosis, in the future.
This trial is categorised as: Type A: No higher than the risk of standard medical care. HMB is a nutritional supplement that is available to the public for purchase without prescription or restriction at health food shops or online vendors. Participants will be monitored for adverse events during trial participation.
There is a risk of bleeding, infection and discomfort from additional blood samples being taken that are not standard of care. Venepuncture is a common procedure that will be carried out by appropriately trained staff at site only. Where routine bloods have been carried out in the 4 weeks before a visit to calculate Child-Pugh and MELD scores, these results may be used for trial data to minimise the amount of blood taken at each visit, where possible. Participants will be informed of risks associated with venepuncture in the PIS (e.g., discomfort, bruising, redness, fainting, vein puncture and swelling at the site where the needle goes in).
Where is the study run from?
Peninsula Clinical Trials Unit (UK)
When is the study starting and how long is it expected to run for?
January 2025 to January 2027
Who is funding the study?
Research for Patient Benefit Programme (UK)
Who is the main contact?
Kayle Sands, boost.penctu@plymouth.ac.uk
Contact information
Scientific
1 Roscoff Rise
Derriford
PL6 5FP
United Kingdom
| Phone | +44 (0)1752 01752 432842 |
|---|---|
| m.kanengoni1@nhs.net |
Principal Investigator
South West Liver Unit
Level 7
Derriford Hospital
Plymouth
PL6 8DH
United Kingdom
| Phone | +44 (0)1752 432 723 |
|---|---|
| ashwin.dhanda@plymouth.ac.uk |
Public
Peninsula Clinical Trials Unit
Faculty of Health
University of Plymouth
N16, ITTC Building 1
Plymouth Science Park
Plymouth
PL6 8BX
United Kingdom
| Phone | +44 (0)1752 437513 |
|---|---|
| boost.penctu@plymouth.ac.uk |
Study information
| Study design | Double-blind randomized placebo-controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Safety, Efficacy |
| Participant information sheet | Not available in web format, please use the contact details to request a participant information sheet |
| Scientific title | β -hydroxy β-methylbutyrate (HMB) supplementation to improve functional status in people with advanced liver cirrhosis: a multicentre double blind placebo-controlled randomised trial: BOOST |
| Study acronym | BOOST |
| Study hypothesis | Primary objective: Determine the clinical effectiveness of HMB supplementation to improve physical function as measured by the Liver Frailty Index. Secondary objectives: 1. To determine the effect of HMB supplementation on: 1.1. Liver disease severity measured by model for end-stage liver disease (MELD) score and Child-Pugh score 1.2. Quality of life and mental wellbeing measured by Short Form-36 (SF-36) and Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS) 1.3. Rate of hospitalisation 1.4. Rate of infections 1.5. Cognitive function, measured by the Animal Naming Test 1.6. Serum short-chain fatty acid concentrations 1.7. Markers of gut permeability (LPS, LBP and D-lactate) 1.8. Muscle mass measured by calf muscle circumference 2. To evaluate participant engagement with trial procedures and adherence to the intervention 3. To assess for contamination, measured by dietary intake (macronutrient intake over the preceding 24 hours at baseline, week 12 and week 24) via Intake24 tool and HMB supplement use. 4. To assess the safety of intervention. |
| Ethics approval(s) |
Approved 06/05/2025, North East - Newcastle & North Tyneside 1 Research Ethics Committee (2nd Floor, 2 Redman Place, Stratford, London, E20 1JQ, United Kingdom; +44 (0)207 104 8384; newcastlenorthtyneside1.rec@hra.nhs.uk), ref: 25/NE/0028 |
| Condition | Advanced liver cirrhosis |
| Intervention | Current interventions as of 09/05/2025: Intervention: 3 g of HMB (nutritional supplement) daily for 12 weeks, oral administration of to 2 x 750 mg capsules twice daily Matched placebo (maltodextrin) Randomisation is via an online tool Follow-up is 24 weeks post-baseline (12 weeks post-treatment). Previous interventions: Intervention: 3 g of HMB (nutritional supplement) daily for 12 weeks, oral administration of 3 x 500 mg capsules twice daily Matched placebo (maltodextrin) Randomisation is via an online tool Follow-up is 24 weeks post-baseline (12 weeks post-treatment). |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Not Applicable |
| Phase | Phase IV |
| Drug / device / biological / vaccine name(s) | Calcium beta-hydroxy-beta-methylbutyrate (CaHMB) |
| Primary outcome measure | Clinical effectiveness of HMB to improve physical function measured by change in Liver Frailty Index at 12 weeks post-baseline* *Note, LFI is measured at baseline, week 12 and week 24 but the primary outcome is baseline vs week 12 |
| Secondary outcome measures | 1. Quality of life measured using the SF-36 questionnaire at Baseline, Weeks 12 and 24 2. Mental wellbeing measured using the WEMWBS at Baseline, Weeks 12 and 24 3. Liver disease severity measured using the Child-Pugh score at Baseline, Weeks 12 and 24 4. Liver disease severity measured using the MELD score at Baseline, Weeks 12 and 24 5. Cognitive function measured using the animal naming test at Baseline, Weeks 12 and 24 6. Serum SCFA concentrations at Baseline, Weeks 12 and 24 7. LPS, LBP and D-lactate concentrations measured using blood test at Baseline, Weeks 12 and 24 8. Muscle mass measured by calf circumference, corrected for BMI and oedema, at Baseline, Weeks 12 and 24 9. Number, duration and diagnosis of any hospital admissions (self-reported) at Weeks 4, 12 and 24 10. Infections (self-reported and by primary/secondary care records) at Weeks 4, 12 and 24 11. Attendance to and completion of the final study visit (Week 24) 12. Self-report of medication adherence at Weeks 4 and 12 13. Medication adherence measured by pill count measured at Week 12 14. Dietary intake measured using a 24-hour food recall (total macronutrient intake/24 hours - protein, carbohydrate, fat, and fibre) at Baseline, Weeks 12 and 24 15. Contamination assessed by checking HMB supplement use at Baseline, Weeks 4, 12 and 24 16. Safety of intervention measured by adverse reactions and serious adverse events measured at Weeks 4, 12 and 24 |
| Overall study start date | 23/01/2025 |
| Overall study end date | 31/01/2027 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Lower age limit | 18 Years |
| Upper age limit | 85 Years |
| Sex | Both |
| Target number of participants | 124 |
| Participant inclusion criteria | Current inclusion criteria as of 09/05/2025: 1. Cirrhosis diagnosed by any of the following: 1.1. Clinical features of cirrhosis as determined by an experienced clinician 1.2. Radiological features on ultrasound or cross-sectional imaging 1.3. Histological evidence of cirrhosis 1.4. Fibrosis assessment by transient elastography with stiffness >15 kPa 2. Advanced cirrhosis defined as Child Pugh score of 7 or more (based on laboratory values and clinical assessment within the previous 6 months) 3. Evidence of portal hypertension within the previous 6 months defined by: 3.1. Presence of ascites 3.2. Presence of oesophageal or gastric varices 3.3. Splenomegaly >13 cm in maximum diameter 3.4. Episode of hepatic encephalopathy 4. Ability to provide informed consent to participate 5. Participant is ≥18 years and ≤85 years of age Previous inclusion criteria: 1. Cirrhosis diagnosed by any of the following: 1.1. Clinical features of cirrhosis as determined by an experienced clinician 1.2. Radiological features on ultrasound or cross-sectional imaging 1.3. Histological evidence of cirrhosis 1.4. Fibrosis assessment by transient elastography with stiffness >15 kPa 2. Advanced cirrhosis defined as Child Pugh score of 7 or more (based on laboratory values and clinical assessment within the previous 6 months) 3. Evidence of portal hypertension within the previous 6 months defined by: 3.1. Presence of ascites 3.2. Presence of oesophageal or gastric varices 3.3. Splenomegaly >13 cm in maximum diameter 3.4. Episode of hepatic encephalopathy 4. Ability to provide informed consent to participate or, where the participant has hepatic encephalopathy, agreement is provided by a personal or professional representative 5. Participant is ≥18 years and ≤85 years of age |
| Participant exclusion criteria | Current exclusion criteria as of 09/05/2025: 1. Estimated prognosis limited to less than 6 months 2. Advanced hepatocellular carcinoma 3. The consumption of HMB, or products containing HMB, within the previous 4 weeks 4. Inability to complete the Liver Frailty Index 5. Liver transplant recipient 6. On the liver transplant waiting list or being considered or under assessment for liver transplant 7. Participant in any other interventional trial within previous 4 weeks 8. Previous history of poor engagement with clinical services, at the discretion of local PI 9. Previous history of hypersensitivity reactions or allergy to exogenous HMB supplements or any of its excipients Previous exclusion criteria: 1. Estimated prognosis limited to less than 6 months 2. Advanced hepatocellular carcinoma 3. The consumption of HMB, or products containing HMB, within the previous 4 weeks 4. Inability to complete the Liver Frailty Index 5. Liver transplant recipient 6. On the liver transplant waiting list or being considered or under assessment for liver transplant 7. Participant in any other interventional trial within previous 4 weeks 8. Previous history of poor engagement with clinical services, at the discretion of local PI |
| Recruitment start date | 01/06/2025 |
| Recruitment end date | 31/05/2026 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Derriford Road
Derriford
Plymouth
PL6 8DH
United Kingdom
Anlaby Road
Hull
HU3 2JZ
United Kingdom
Lower Ln
Fazakerley
Liverpool
L9 7AL
United Kingdom
Queens Medical Centre
Derby Road
Nottingham
NG7 2UH
United Kingdom
Barrack Road
Exeter
EX2 5DW
United Kingdom
Blackshaw Road
Tooting
London
SW17 0QT
United Kingdom
Gartnavel Royal Hospital
1055 Great Western Road Glasgow
Glasgow
G12 0XH
United Kingdom
Wolverhampton Road
Heath Town
Wolverhampton
WV10 0QP
United Kingdom
Sponsor information
Hospital/treatment centre
Plymouth Science Park
Plymouth
PL6 8BX
England
United Kingdom
| plh-tr.rdgovernance@nhs.net | |
| Website | http://www.plymouthhospitals.nhs.uk/home |
"ROR" |
https://ror.org/05x3jck08 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- NIHR Research for Patient Benefit Programme, RfPB
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 16/03/2027 |
|---|---|
| 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 | Peer-reviewed scientific journals Conference presentation Publication on website Submission to regulatory authorities Access to raw data and right to publish freely by all investigators in the study or by the Independent Steering Committee on behalf of all investigators Other After the trial has been reported, the anonymised individual participant data that underlie the results will be available on request from the CI and Sponsor, along with supplementary files as required (e.g. data dictionaries, blank data collection forms, analysis code, etc). Data will be shared with (or access to the data will be provided to) requestors whose proposed use of the data has been approved by the CI and Sponsor, under an appropriate data-sharing agreement. It will not be possible to identify participants personally from any information shared. |
| IPD sharing plan | The data-sharing plans for the current study are unknown and will be made available at a later date |
Editorial Notes
09/05/2025: The following changes were made to the study record:
1. Ethics approval details added.
2. The interventions, inclusion and exclusion criteria were updated.
3. The study participating centres were updated to remove University Hospitals Birmingham NHS Foundation Trust and add Royal Wolverhampton NHS Trust.
27/01/2025: Study's existence confirmed by the HRA.
