Can metformin prevent worsening of muscle weakness and frailty in older people who are showing early signs of frailty?
| ISRCTN | ISRCTN29932357 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN29932357 |
| EudraCT/CTIS number | 2020-004023-16 |
| IRAS number | 275219 |
| Secondary identifying numbers | CPMS 47772, IRAS 275219 |
- Submission date
- 10/04/2020
- Registration date
- 21/01/2021
- Last edited
- 23/01/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Signs and Symptoms
Plain English Summary
Background and study aims
Frailty is a condition where the body isn’t able to cope with a problem such as an injury, mild infection or other illness. Some of the first signs are losing muscle strength and slower walking. It is not yet known how best to prevent the onset of frailty. Exercise can help, and diet may also play a part. These approaches only go so far though, and new approaches including medication are also needed. Metformin is a medication that may be promising to prevent frailty by improving muscle function.
This project will test whether metformin, a medicine normally used to treat diabetes, can improve physical function in older people without diabetes at risk of developing frailty or sarcopenia (muscle weakness).
Who can participate?
People living in the North East of England aged 65 years or older who walk slowly and have low muscle strength, which means they are at risk of becoming frail, and who do not have diabetes.
What does the study involve?
Participants will be randomly allocated to one of two groups. One group will take a metformin tablet three times a day for 4 months. The other group will take a placebo (dummy) tablet three times a day for 4 months. Neither the participants nor the research team will know who is taking which tablet until the end of the study.
The researchers will measure walking speed, handgrip strength and other aspects of frailty and muscle weakness at the start and after 4 months of treatment. They will also measure activities of daily living, quality of life, muscle size, side effects of medication, and a series of blood tests to understand who might respond best to metformin to help select participants for a future large study.
What are the possible benefits and risks of participating?
Metformin is a safe medication that has been used by millions of people for over 50 years. It can cause loose bowel motions or nausea in some people, but the researchers will minimise the chances of this happening by using a low dose, and excluding anyone with recent diarrhoea. Very rarely, metformin can cause a build up of acid in the blood (acidosis). The researchers will monitor this at the monthly visits, and they will also exclude people with poor kidney function, who may have problems expelling metformin from the body, which can increase the chances of metformin causing a build-up of acid.
Where is the study run from?
Newcastle upon Tyne Hospitals NHS Foundation Trust (UK)
When is the study starting and how long is it expected to run for?
April 2020 to August 2023
Who is funding the study?
NIHR Newcastle Biomedical Research Centre (UK)
Who is the main contact?
Professor Miles Witham, Miles.Witham@newcastle.ac.uk
Contact information
Public
Campus for Ageing and Vitality
Newcastle
NE4 5PL
United Kingdom
 ORCID ID |
0000-0002-1967-0990 |
|---|---|
| Phone | +44 (0)1912081317 |
| Miles.Witham@newcastle.ac.uk |
Study information
| Study design | Randomized, placebo-controlled, double-blind, parallel-group trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Community |
| Study type | Prevention |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet. |
| Scientific title | Metformin to prevent progression of sarcopenia and frailty for older people – a randomised controlled proof of concept trial |
| Study acronym | MET-PREVENT |
| Study hypothesis | 4 months of metformin 500 mg three times a day will improve measures of physical performance in older people with sarcopenia and prefrailty. |
| Ethics approval(s) | Approved 07/01/2021, North West - Liverpool Central Research Ethics Committee (**Currently being held remotely via Teleconference/ZOOM** Liverpool Women's Hospital, +44 (0)207 104 8197, +44 (0)2071048387; liverpoolcentral.rec@hra.nhs.uk), ref: 20/NW/0470 |
| Condition | Frailty and sarcopenia in older people |
| Intervention | Participants will be randomised 1:1 into the metformin or placebo arms using a web-based randomisation system. They will receive metformin hydrochloride 500 mg or matching placebo three times a day for 4 months. Assessments will be conducted at baseline and 4 months (all outcomes) with an additional safety assessment visit at 1 month. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase IV |
| Drug / device / biological / vaccine name(s) | Metformin hydrochloride |
| Primary outcome measure | 4-m walk speed at 4 months |
| Secondary outcome measures | 1. Fried frailty score, including individual components: 1.1. Activity level assessed using self-report questionnaire at baseline and 4 months 1.2. Exhaustion assessed using self-report questionnaire at baseline and 4 months 1.3. Grip strength assessed using Jamar handgrip dynamometer at baseline and 4 months 1.4. 4-m walk speed assessed using timed walk test over 4 m at baseline and 4 months 1.5. Weight assessed using calibrated scales at baseline and 4 months 2. Transitions from pre-frail to frail, death, inability to continue in trial, or to non-frail from baseline to 4 months 3. Lower limb muscle power measured using Short Physical Performance Battery at baseline and 4 months 4. 6-min walk distance assessed at baseline and 4 months 5. Total body muscle mass measured using bioimpedance at baseline and 4 months 6. Ability to perform activities of daily living assessed using the Nottingham Extended Activities of Daily Living Scale (EADL) at baseline and 4 months 7. Health related quality of life assessed using the EQ5D and SF-36 scales at baseline and 4 months 8. Trial metrics: 8.1. Conversion from screening to randomisation assessed using study records at screening and baseline study visits 8.2. Recruitment rate assessed using study records over the 10-month recruitment period 8.3. Retention rate assessed using study records over the 4-month participation period |
| Overall study start date | 01/04/2020 |
| Overall study end date | 31/08/2023 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Senior |
| Lower age limit | 65 Years |
| Sex | Both |
| Target number of participants | 80 |
| Total final enrolment | 72 |
| Participant inclusion criteria | 1. Aged 65 years or over 2. Low maximum handgrip strength (<16 kg for women, <27 kg for men) 3. Walk speed <0.8 m/s on 4-m walk test |
| Participant exclusion criteria | 1. Diabetes mellitus (type 1 or type 2) 2. eGFR <45 ml/min/1.73 m2 by MDRD4 or CKD-EPI equation 3. History of diarrhoeal illness within the last 3 months (>48 h of Bristol stool chart grade 6 or 7 ) 4. Alcohol intake >21 units/week (women) or >35 units/week (men) 5. Symptomatic chronic heart failure, diagnosed according to European Society of Cardiology guidelines (asymptomatic left ventricular systolic dysfunction will not be an exclusion criterion) 6. Liver function tests (bilirubin, alanine aminotransferase or alkaline phosphatase) >3x upper limit of normal 7. Oral steroid dose >7.5 mg prednisolone equivalent per day 8. Unable to mobilise without human assistance 9. Life expectancy of <3 months as adjudicated by the local investigator 10. Unable to give written informed consent 11. Previous intolerance of metformin or taking metformin for another condition 12. Currently participating in, or participated within 30 days, another intervention study (observational studies and registries are permitted) |
| Recruitment start date | 01/04/2021 |
| Recruitment end date | 30/09/2022 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Newcastle University
Newcastle upon Tyne
NE4 5PL
United Kingdom
Gateshead
NE9 6SX
United Kingdom
Sponsor information
Hospital/treatment centre
Newcastle Joint Research Office
Regent Point
Regent Road
Newcastle upon Tyne
NE3 3HD
England
United Kingdom
| Phone | +44 (0)191 282 4461 |
|---|---|
| sean.scott@nhs.net | |
| Website | http://www.newcastle-hospitals.org.uk/ |
"ROR" |
https://ror.org/05p40t847 |
Funders
Funder type
Research organisation
Private sector organisation / Research institutes and centers
- Alternative name(s)
- Newcastle Biomedical Research Centre, Newcastle NIHR Biomedical Research Centre
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/01/2024 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Main trial results will be published within 18 months of the end of the trial, and results will be presented as a conference abstract within 12 months of the end of the trial. Results will be fed back to participants via a newsletter and an in-person end-of-study event. |
| IPD sharing plan | The datasets generated during the current study will be available upon request from the Chief Investigator (Professor Miles Witham, Miles.Witham@newcastle.ac.uk). Deidentified, individual participant-level data will be available to bona-fide academic research teams from 12 months after the end of the trial, subject to submission of an outline of the purpose for which it will be used, and subject to approval by a Data Access Committee process hosted by the trial funder (NIHR Newcastle Biomedical Research Centre). Consent will be obtained from participants for this data sharing. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No | ||
| Protocol article | 18/07/2022 | 18/08/2023 | Yes | No | |
| Basic results | 19/12/2023 | 19/12/2023 | No | No | |
| Plain English results | 23/01/2024 | 23/01/2024 | No | Yes |
Additional files
Editorial Notes
23/01/2024: Plain English results uploaded.
19/12/2023: Basic results uploaded.
18/08/2023: The following changes were made to the trial record:
1. Publication reference added.
2. The intention to publish date was changed from 31/08/2023 to 31/01/2024.
20/10/2022: The recruitment end date has been changed from 31/10/2022 to 30/09/2022. Total final enrolment added.
20/06/2022: The recruitment end date has been changed from 30/06/2022 to 31/10/2022.
13/12/2021: The recruitment end date was changed from 31/12/2021 to 30/06/2022.
21/01/2021: Trial’s existence confirmed by the National Institute for Health Research (NIHR).
