Metformin Immunotherapy in HIV Infection

March 13, 2023 updated by: Jean-Pierre Routy, McGill University Health Centre/Research Institute of the McGill University Health Centre

The Effect of Metformin on HIV Reservoir Size in Non-diabetic Antiretroviral Therapy (ART) Treated Participants: the Lilac Study

Anti-HIV drugs cut down the number of serious infections that people with HIV get. However, some subjects taking anti-HIV drugs do not achieve adequate cluster of differentiation 4 (CD4) recovery and decrease in elevated cluster of differentiation 8 (CD8) cells. Such patients with a low CD4/CD8 ratio remain at risk for developing acquired immune deficiency syndrome (AIDS) and non-AIDS-related complications. Two of the most important factors associated with low CD4/CD8 ratio include: the persistence of HIV on ART and inflammation.

Metformin, the most widely used medication to treat type 2 diabetes, is well tolerated with minimal side effects. It has been linked to anti-aging and weight reducing properties in non-diabetic persons. Because of its ability to improve immune functions, metformin could be a promising addition to ART in HIV patients. It is also reported to change the composition of microbes in the gut which may improve inflammation.

PURPOSES OF THE STUDY

The purposes of this study are to find out if:

  1. metformin can be combined with anti-HIV drugs to reduce the amount of hidden virus in the body;
  2. metformin can be combined with anti-HIV drugs to improve immune function.
  3. metformin can be combined with anti-HIV drugs to impact CD4 T cell count and CD4/CD8 T cell ratio during treatment and after its discontinuation
  4. metformin can change the composition of the bacteria in the gut which may improve inflammation.

For this purpose, the investigators will add metformin at the usual antidiabetic dose for 12 weeks for patients receiving stable ART, having a CD4/CD8 ratio below 0.7.

Approximately 22 participants will be enrolled in this study at the Chronic Viral Illness Service of the McGill University Health Centre, the Ottawa Hospital and the Maple Leaf Medical Clinic (Toronto). This study will last about 24 weeks; metformin treatment will be for 12 weeks. In order to be eligible for the study, the participants must be 18 years of age or older, have an undetectable viral load (the quantity of the HIV virus in the blood must be less than 50 copies/ml) for at least 3 months and have a CD4/CD8 ratio of less than 0.7. All participants will also be asked to give blood and stool samples and optional colon mucosal biopsy samples (before and after metformin supplementation) to study the size of the viral reservoir and the amount of T cell activation and changes in gut microbiota composition.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

22

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Quebec
      • Montreal, Quebec, Canada, H4A 3J1
        • Chronic Viral Illness Service, McGill University Health Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. HIV-1 infected male or female adults greater than or equal to 18 years of age
  2. HIV-1 infected adults successfully treated with ART for at least 3 years (the time necessary to establish a stable reservoir)
  3. Individuals on a stable ART regimen for at least 3 months, with plasma viral load below the level of detection and with a CD4/CD8 ratio ≤ 0.7
  4. Non-diabetic (HbA1c < 5.9%) and pre-diabetic individuals (HbA1c between 6.0 and ≥ 6.4%), as defined by their glycosylated hemoglobin levels
  5. Able to understand and sign the informed consent form prior to screening

Exclusion Criteria:

  1. Individuals with a known hypersensitivity/allergy to the metformin
  2. Individuals who are actively participating in an experimental therapy study or who have received experimental therapy within the last 6 months
  3. Individuals who are suffering from severe systemic diseases (uncontrolled hypertension, chronic renal failure), or active uncontrolled infections
  4. Individuals having diabetes mellitus (HbA1c ≥ 6.5 %) as defined by the Canadian Clinical Practice Guidelines for the Prevention and Management of Diabetes

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Metformin
Assessment will be done at the baseline, during and after 12 week of metformin use.
Drug: Metformin
Metformin hydrochloride is a white to off-white crystalline compound formulated as tablets for oral consumption; tablets contain 500 mg, 850 mg, or 1000 mg of metformin hydrochloride. Only 500 mg and 850 mg tablets will be used for this study.
Other Names:
  • Glucophage

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Decrease in the size of the HIV reservoir
Time Frame: 12 weeks
12 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Change in the percentage of activated CD8 T-cells
Time Frame: 12 weeks
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

McGill University Health Centre/Research Institute of the McGill University Health Centre

Investigators

  • Principal Investigator: Jean-Pierre Routy, MD; FRCPC, McGill University Health Centre/Research Institute of the McGill University Health Centre

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2016

Primary Completion (Actual)

August 14, 2018

Study Completion (Actual)

February 1, 2020

Study Registration Dates

First Submitted

January 15, 2016

First Submitted That Met QC Criteria

January 15, 2016

First Posted (Estimate)

January 20, 2016

Study Record Updates

Last Update Posted (Actual)

March 14, 2023

Last Update Submitted That Met QC Criteria

March 13, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CTNPT027

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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