Condition category
Nutritional, Metabolic, Endocrine
Date applied
27/06/2020
Date assigned
09/07/2020
Last edited
10/07/2020
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Not yet recruiting

Plain English Summary

Background and study aims
The numbers of people with type 2 diabetes in Africa are rising rapidly. People who are living with HIV and have been on treatment for HIV seem to be at high risk for developing diabetes. 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. We will be testing whether Metformin can stop or delay a person developing diabetes. Metformin has been tested for this purpose in high-income countries, but not in Africa and not 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 and who have pre-diabetes.

What does the study involve?
We will screen people in HIV treatment programmes to identify those who have prediabetes. Screening will be done using both the fasting glucose and the oral glucose tolerance tests. If patients agree to take part in the study, we will allocate them at random to one of two groups. One group will receive a slow-release preparation of metformin which only needs to be taken once a day; and the other 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 3 years. At the end of the study and at yearly intervals during the study, we will test the blood sugar levels in the participants. We will use the oral glucose tolerance test to do this. This is the gold standard for testing for diabetes. The primary objective of the trial is to determine the number of participants who develop diabetes in the two groups over the 3-year follow-up period.
All participants in the trial will receive basic advice on diet and lifestyle to prevent diabetes.

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 all participants in the study closely.

Where is the study run from?
This study will be run from Liverpool in the UK and the Republic of Tanzania in East Africa. In Tanzania we will recruit patients for this study from 6 sites in Dar es Salaam. These are Amana Regional Referral hospital, Temeke Regional Referral Hospital, Mwanyanamala Hospital, Mnazi Moja Hospital, Mbagala Rangi Tatu Hospital and the Shree Hindu Mandal Hospital.

When is the study starting and how long is it expected to run for?
Preparation for this study began in April 2020. Testing of patients to see who would be able to join the study will begin in early 2021, and the follow up of the all participants will be complete by the end of 2024.

Who is funding the study?
This study is funded by a grant from the European & Developing Countries Clinical Trial Partnership (EDCTP).

Who is the main contact?
Prof Shabbar Jaffar, shabbar.jaffar@lstmed.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Prof Shabbar Jaffar

ORCID ID

http://orcid.org/0000-0002-9615-1588

Contact details

Liverpool School of Tropical Medicine
Liverpool
L3 5QA
United Kingdom
+44 (0)151 705 2591
shabbar.jaffar@lstmed.ac.uk

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

Nil known

Study information

Scientific title

Preventing and delaying the development of diabetes in Africa: a randomised placebo-controlled double-blind phase III trial of metformin in people living with HIV-infection and pre-diabetes.

Acronym

META

Study hypothesis

Can treatment with Metformin prevent or delay the development of diabetes among HIV-infected persons on antiretroviral therapy in Africa?

Ethics approval

1. Approval pending, Research Ethics Committee of the Liverpool School of Tropical Medicine
2. Approval pending, Medical Research Coordinating Committee of the National Institute of Medical Research of Tanzania

Study design

Randomized placebo-controlled double-blind phase III 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, HIV-infection

Intervention

Metformin extended release at a dose of 2000mg per day and matching placebo. The follow up period will be three years. Eligible patients will be randomised using permuted blocks in a 1:1 ratio, stratified by health facility and sex.
All participants in the trial will receive basic advice on diet and lifestyle to prevent diabetes.

Intervention type

Drug

Phase

Phase III

Drug names

Metformin extended release

Primary outcome measure

Incidence of diabetes, measured over a 36-month follow-up period. The diagnosis of diabetes will be made using an oral glucose tolerance test, which will be conducted annually

Secondary outcome measures

1. Prevalence and incidence of glycaemia related complications, measured at the start and end of the study, and at any point during follow up where clinically indicated. The study will assess for the following diabetes related complications:
1.1. Retinopathy using retinal photography
1.2. Neuropathy using the Neuropathy Disability Score and the Diabetic Neuropathy Symptom Score
1.3. Nephropathy using serial assessment of eGFR
2. Time to diabetes-free survival, measured at the end of study follow up
3. Cost consequences. Costs associated with lost productivity, and health services and social care resource use will be collected, during and at the end of the study
4. Health-related quality-of-life, measured using EuroQol EQ-5D and 12-item Short Form-12
5. Cost-effectiveness, measured at the end of study follow up. Information on costs will be collected using economic patient questionnaires to measure patients related costs (out-of-pocket expenses, costs associated with lost productivity) as well as costs of all resources used by patients (health service and social care resource use costs). The collected costs and health outcomes will be used to estimate possible cost savings and/or cost-effectiveness of metformin (i.e., cost changes per patient, cost per diabetes case prevented, and QALYs gained).

Overall trial start date

01/04/2020

Overall trial end date

31/12/2024

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. HIV-positive and stable on the same antiretroviral therapy for at least 6-months
2. Attending the HIV clinic regularly for at least 6 months
3. Impaired fasting glucose of between 6.1 to 6.9 mmol/L and/or impaired glucose tolerance at 2 hours of 7.8 to 11.10 mmol/L
4. Planning to remain in the area for > 1 year
5. Willing to provide written informed consent

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

2,000

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

01/02/2021

Recruitment end date

31/10/2021

Locations

Countries of recruitment

Tanzania

Trial participating centre

Amana Hospital
Uhuru Street
Dar es Salaam
-
Tanzania

Trial participating centre

Hindu Mandal Hospital
Chusi Street
Dar es Salaam
-
Tanzania

Trial participating centre

Mwananyamala Hospital
61665 Kinondoni
Dar es Salaam
-
Tanzania

Trial participating centre

Temeke Regional Referral Hospital
Temeke Street Temeke District
Dar es Salaam
-
Tanzania

Trial participating centre

Mbagala Rangi Tatu Hospital
Mbagala Road Temeke district
Dar es Salaam
-
Tanzania

Trial participating centre

Mnazi Moja Hospital
Bibi Titi Mohamed Road
Dar es Salaam
-
Tanzania

Sponsor information

Organisation

Liverpool School of Tropical Medicine

Sponsor details

Pembroke Place
Liverpool
L3 5QA
United Kingdom
+44 (0)151 705 3100
info@lstmed.ac.uk

Sponsor type

University/education

Website

http://www.lstmed.ac.uk/

Funders

Funder type

Charity

Funder name

European and Developing Countries Clinical Trials Partnership

Alternative name(s)

A Parceria entre a Europa e os Países em Desenvolvimento para a Realização de Ensaios Clínicos, The European & Developing Countries Clinical Trials Partnership, Le partenariat Europe-Pays en développement pour les essais cliniques, EDCTP

Funding Body Type

private sector organisation

Funding Body Subtype

International organizations

Location

Netherlands

Results and Publications

Publication and dissemination plan

A publication policy is in preparation. It is intended that study findings will be published in a high-impact peer-reviewed journal. Research papers will be Open Access. Research data will also be made open access in accordance with EDCTP guidelines on data sharing.
Dissemination will be done through academic channels (peer-reviewed journal publications, conference abstracts/proceedings), the project website, public and professional seminars, factsheets, social media and press activities.

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

31/12/2024

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

10/07/2020: Internal review. 09/07/2020: Trial’s existence confirmed by European Union Horizon 2020.