Plain English Summary
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?
We anticipate the study will start in April 2019 and run until April 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).
Trial website
Contact information
Type
Scientific
Primary contact
Prof Shabbar Jaffar
ORCID ID
Contact details
Liverpool School of Tropical Medicine
Liverpool
L3 5QA
United Kingdom
+44 151 705 2591
shabbar.jaffar@lstmed.ac.uk
Additional identifiers
EudraCT number
Nil known
ClinicalTrials.gov number
Nil known
Protocol/serial number
Protocol version 12
Study information
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.
Acronym
META
Study hypothesis
Metformin significantly reduces progression to diabetes in prediabetic HIV infected persons on antiretroviral therapy compared to Placebo.
Ethics approval
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
Study design
Randomised placebo-controlled double-blind trial.
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Prevention
Patient information sheet
Not available in web format, please use contact details to request a participant information sheet.
Condition
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
Phase
Phase II
Drug names
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 trial start date
01/04/2019
Overall trial end date
30/04/2021
Reason abandoned (if study stopped)
Eligibility
Participant 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
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
360
Participant 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.
Recruitment start date
01/10/2019
Recruitment end date
01/04/2020
Locations
Countries of recruitment
Tanzania
Trial participating centre
Hindu Mandal Hospital
Chusi Street
Dar es Salaam
-
Tanzania
Trial participating centre
Amana Hospital
Uhuru Street
Dar es Salaam
-
Tanzania
Trial participating centre
Temeke Regional Referral Hospital
Temeke Street
Dar es Salaam
-
Tanzania
Trial participating centre
Mwanyanamala Hospital
61665 Kinondoni
Dar es Salaam
-
Tanzania
Sponsor information
Organisation
Liverpool School of Tropical Medicine
Sponsor details
Pembroke Place
Liverpool
L3 5QA
United Kingdom
+44 151 705 2591
shabbar.jaffar@lstmed.ac.uk
Sponsor type
University/education
Website
Funders
Funder type
Government
Funder name
National Institute for Health Research
Alternative name(s)
NIHR
Funding Body Type
government organisation
Funding Body Subtype
National government
Location
United Kingdom
Results and Publications
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 statement:
The current data sharing plans for this study are unknown and will be available at a later date
Intention to publish date
01/10/2021
Participant level data
To be made available at a later date
Basic results (scientific)
Publication list