Condition category
Nutritional, Metabolic, Endocrine
Date applied
08/03/2019
Date assigned
22/03/2019
Last edited
21/03/2019
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
No longer recruiting

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 2 hospitals in Dar es Salaam, the Hindu Mandal Hospital and Amana Hospital. Both 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 June 2020.

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 Trial

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

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

01/06/2020

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

01/04/2019

Recruitment end date

01/06/2019

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

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

www.lstmed.ac.uk

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 - around July 2020. 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

15/07/2020

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

19/03/2019: Trial’s existence confirmed by IRB