Metformin treatment for diabetes prevention in Africa
| ISRCTN | ISRCTN76157257 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN76157257 |
| Secondary identifying numbers | Protocol version 14 |
- Submission date
- 08/03/2019
- Registration date
- 22/03/2019
- Last edited
- 18/07/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nutritional, Metabolic, Endocrine
Plain English summary of protocol
Background and study aims
The numbers of people with type 2 diabetes in Africa are rising rapidly. We are looking for ways to prevent people who have already have raised blood sugar (called prediabetes), from going on to develop diabetes.
We will test a drug called metformin in HIV infected persons with pre-diabetes to see what effect, if any, it has on blood glucose. If the drug is able to lower their blood sugar levels, and appears to be safe, we hope to go on to test whether the drug can stop or delay a person developing diabetes in a subsequent large trial. Metformin has been tested for this purpose in high-income countries countries, but not in Africa among those who are on HIV treatment. The study will be conducted in Tanzania.
Who can participate?
Adults over the age of 18, who are HIV-infected and have been stable on treatment for HIV-infection for a minimum of 6 months.
What does the study involve?
We will screen people in HIV treatment programmes to identify those who are prediabetic. If they agree to take part in the study, we will allocate them at random to one of two groups. The first group will receive a slow-release preparation of metformin which only needs to be taken once a day; and the second group will receive a placebo that looks like the metformin and also is taken once a day. Neither the patient or the doctors will know who is receiving the drug and who is receiving the placebo (this is called a randomised double-blind placebo-controlled trial). Each participant will be followed up for 12 months, and at the end we will assess blood sugar levels in those who received metformin compared to those who received the placebo.
What are the possible benefits and risks of participating?
The benefits of participating are that the study will provide information on a possible prevention strategy for those that are at risk of developing diabetes. There are risks associated with taking metformin. A proportion of people who take this drug experience side effects, particularly of the gastro-intestinal system like nausea, abdominal pain, vomiting and diarrhoea, although these symptoms should decrease with time. There are also more serious side effects like the development of a condition calls lactic acidosis, but is very rare and unlikely to occur. We will be monitoring the study closely.
Where is the study run from?
From 4 hospitals in Dar es Salaam, the Hindu Mandal Hospital, Amana Hospital, Temeke Regional Referral Hospital, and Mwanyanamala Hospital. All are in Tanzania
When is the study starting and how long is it expected to run for?
April 2019 to October 2021
Who is funding the study?
The National Institute for Health Research (NIHR).
Who is the main contact?
Prof Shabbar Jaffar at LSTM (Shabbar.jaffar@lstmed.ac.uk).
Contact information
Scientific
Director UCL Institute of Global Health
30 Guildford Street
London
WC1N 1EH
United Kingdom
 ORCID ID |
0000-0002-9615-1588 |
|---|---|
| Phone | +44 (0)20 7679 2352 |
| s.jaffar@ucl.ac.uk |
Study information
| Study design | Randomised placebo-controlled double-blind trial. |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Prevention |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet. |
| Scientific title | A randomised placebo-controlled double-blind phase II trial to determine the effects of metformin versus placebo on glycaemia in HIV-infected persons with pre-diabetes in Tanzania. |
| Study acronym | META |
| Study objectives | Metformin significantly reduces progression to diabetes in prediabetic HIV infected persons on antiretroviral therapy compared to Placebo. |
| Ethics approval(s) | Liverpool School of Tropical Medicine (LSTM) Research Ethics Committee; reference (17-078) National Institute of Medical Research and the Ministry of Health, Community Development, Gender, Elderly and Children. Tanzania Food and Drug Authority |
| Health condition(s) or problem(s) studied | Prediabetes in person who are on HIV treatment |
| Intervention | The intervention will be Metformin hydrochloride slow-release preparation, 2000 mg per day, compared with a matching placebo. The treatment will only be taken once a day. Participants who are HIV infected and on treatment, found to be prediabetic on screening, will be randomised using permuted block randomisation with varying block sizes chosen at random using the SAS software. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Metformin hydrochloride, slow release preparation |
| Primary outcome measure | Glycaemia at 12 months as ascertained by the oral glucose tolerance test. |
| Secondary outcome measures | Current secondary outcome measures as of 20/05/2020: 1. Changes in glycaemia from baseline as ascertained by the oral glucose tolerance test at 6 and 12 months 2. Incidence of adverse events assessed using patient notes at 12 months 3. Rates of retention in care assessed using patient notes at 12 months 4. Estimated adherence to study drugs assessed using patient notes at 12 months Previous secondary outcome measures: 1. Changes in glycaemia from baseline as ascertained by the oral glucose tolerance test 2. Incidence of adverse events assessed using patient notes at 12 months 3. Rates of retention in care assessed using patient notes at 12 months 4. Estimated adherence to study drugs assessed using patient notes at 12 months |
| Overall study start date | 01/04/2019 |
| Completion date | 26/10/2021 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 360 |
| Total final enrolment | 364 |
| Key inclusion criteria | 1. HIV-positive on antiretroviral therapy (ART) for at least 6 months and considered stable on treatment (i.e. in regular attendance for care). 2. BMI>30 combined with either impaired fasting glucose (6.1 to 6.9 mmol/L) and/or impaired glucose tolerance at 2 hours (7.0 to 11.10 mmol/L) 3. BMI<=30 combined with either impaired fasting glucose (6.3 to 6.9 mmol/L) and/or impaired glucose tolerance at 2 hours (9.0 to 11.10 mmol/L) 4. Planning to remain in the area for > 6-months 5. Written informed consent |
| Key exclusion criteria | 1. Pregnant women 2. Renal disease or renal dysfunction (eGFR<45) 3. Signs and symptoms of any form of acute metabolic acidosis including lactic acidosis and diabetic ketoacidosis 4. Other acute conditions with: 4.1 the potential to alter renal function including: dehydration, severe infection or shock 4.2 the potential to cause tissue hypoxia including decompensated heart failure, respiratory failure, recent myocardial infarction, shock 5. Congestive heart failure requiring pharmacological treatment 6. Clinical evidence of liver disease 7. Evidence of alcoholism or acute alcohol intoxication 8. Known hypersensitivity to metformin or any excipients associated with the preparation (in this case: Magnesium stearate, sodium carboxymethylcellulose, hypromellose) 9. Other acute conditions requiring hospital admission. |
| Date of first enrolment | 05/11/2019 |
| Date of final enrolment | 24/07/2020 |
Locations
Countries of recruitment
- Tanzania
Study participating centres
Dar es Salaam
-
Tanzania
Dar es Salaam
-
Tanzania
Dar es Salaam
-
Tanzania
Dar es Salaam
-
Tanzania
Sponsor information
University/education
Pembroke Place
Liverpool
L3 5QA
England
United Kingdom
| Phone | +44 151 705 2591 |
|---|---|
| shabbar.jaffar@lstmed.ac.uk | |
| Website | www.lstmed.ac.uk |
"ROR" |
https://ror.org/03svjbs84 |
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
Results and Publications
| Intention to publish date | 30/06/2022 |
|---|---|
| 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 to publish one paper in a high impact peer-reviewed journal shortly after the end of the trial. The paper will include the main efficacy findings. |
| IPD sharing plan | The current data sharing plans for this study are unknown and will be available at a later date |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | 18/07/2023 | 18/07/2023 | Yes | No |
Editorial Notes
18/07/2023: Publication reference added.
12/12/2022: The scientific contact was updated.
19/01/2022: The following changes were made to the trial record:
1. The overall end date was changed from 30/09/2021 to 26/10/2021.
2. The intention to publish date was changed from 30/11/2021 to 30/06/2022.
3. The plain English summary was updated to reflect these changes.
01/09/2021: The following changes were made to the trial record:
1. The overall end date was changed from 31/08/2021 to 30/09/2021.
2. The intention to publish date was changed from 01/10/2021 to 30/11/2021.
3. The plain English summary was updated to reflect these changes.
24/03/2021: The total final enrolment was added.
23/03/2021: The following changes were made to the trial record:
1. The contact details were updated.
2. The recruitment start date was changed from 01/10/2019 to 05/11/2019.
3. The recruitment end date was changed from 01/04/2020 to 24/07/2020.
4. The overall end date was changed from 30/04/2021 to 31/08/2021.
5. The plain English summary was updated to reflect these changes.
20/05/2020: The following changes were made to the trial record:
1. The recruitment end date was changed from 01/04/2020 to 01/04/2020.
2. The secondary outcome measures have been updated.
3. The trial participating centres "Temeke Regional Referral Hospital" and "Mwanyanamala Hospital" have been added.
4. The plain English summary has been updated to reflect the changes above.
16/08/2019: The following changes were made to the trial record:
1. The recruitment start date was changed from 01/04/2019 to 01/10/2019.
2. The recruitment end date was changed from 01/06/2019 to 01/04/2020.
3. The overall trial end date was changed from 01/06/2020 to 30/04/2021.
4. The intention to publish date was changed from 15/07/2020 to 01/10/2021.
19/03/2019: Trial’s existence confirmed by IRB.
