Metformin Immunotherapy in HIV Infection

NCT02659306 | Completed Phase 1 DMC

• 1 other identifier: CTNPT027
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

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. 1.metformin can be combined with anti-HIV drugs to reduce the amount of hidden virus in the body;
2. 2.metformin can be combined with anti-HIV drugs to improve immune function.
3. 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. 4.metformin can change the composition of the bacteria in the gut which may improve inflammation.

Conditions

HIV Infection

Outcome Measures

Primary Outcomes (1)

• Decrease in the size of the HIV reservoir

  12 weeks

Secondary Outcomes (1)

• Change in the percentage of activated CD8 T-cells

  12 weeks

Study Arms (1)

Metformin

EXPERIMENTAL

Assessment will be done at the baseline, during and after 12 week of metformin use.

Drug: Metformin

Interventions

Metformin DRUG

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.

Also known as: Glucophage

Metformin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HIV-1 infected male or female adults greater than or equal to 18 years of age
• HIV-1 infected adults successfully treated with ART for at least 3 years (the time necessary to establish a stable reservoir)
• 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
• Non-diabetic (HbA1c \< 5.9%) and pre-diabetic individuals (HbA1c between 6.0 and ≥ 6.4%), as defined by their glycosylated hemoglobin levels
• Able to understand and sign the informed consent form prior to screening

You may not qualify if:

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

Sponsors & Collaborators

• McGill University Health Centre/Research Institute of the McGill University Health Centre: lead

Study Sites (1)

Chronic Viral Illness Service, McGill University Health Centre

Montreal, Quebec, H4A 3J1, Canada

Location

Related Publications (5)

• Routy JP, Mehraj V, Cao W. HIV immunotherapy comes of age: implications for prevention, treatment and cure. Expert Rev Clin Immunol. 2016;12(2):91-4. doi: 10.1586/1744666X.2016.1112269. Epub 2015 Dec 2.

  PMID: 26629806 BACKGROUND

• Lu W, Mehraj V, Vyboh K, Cao W, Li T, Routy JP. CD4:CD8 ratio as a frontier marker for clinical outcome, immune dysfunction and viral reservoir size in virologically suppressed HIV-positive patients. J Int AIDS Soc. 2015 Jun 29;18(1):20052. doi: 10.7448/IAS.18.1.20052. eCollection 2015.

  PMID: 26130226 BACKGROUND

• Vyboh K, Jenabian MA, Mehraj V, Routy JP. HIV and the gut microbiota, partners in crime: breaking the vicious cycle to unearth new therapeutic targets. J Immunol Res. 2015;2015:614127. doi: 10.1155/2015/614127. Epub 2015 Feb 22.

  PMID: 25759844 BACKGROUND

• Dagenais-Lussier X, Mouna A, Routy JP, Tremblay C, Sekaly RP, El-Far M, Grevenynghe Jv. Current topics in HIV-1 pathogenesis: The emergence of deregulated immuno-metabolism in HIV-infected subjects. Cytokine Growth Factor Rev. 2015 Dec;26(6):603-13. doi: 10.1016/j.cytogfr.2015.09.001. Epub 2015 Sep 8.

  PMID: 26409789 BACKGROUND

• Routy JP, Isnard S, Mehraj V, Ostrowski M, Chomont N, Ancuta P, Ponte R, Planas D, Dupuy FP, Angel JB; Lilac Study Group. Effect of metformin on the size of the HIV reservoir in non-diabetic ART-treated individuals: single-arm non-randomised Lilac pilot study protocol. BMJ Open. 2019 Apr 20;9(4):e028444. doi: 10.1136/bmjopen-2018-028444.

  PMID: 31005944 DERIVED

Related Links

• The Canadian HIV Trials Network

MeSH Terms

Conditions

HIV Infections

Interventions

Metformin

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Jean-Pierre Routy, MD; FRCPC

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 15, 2016
• First Posted: January 20, 2016
• Study Start: September 1, 2016
• Primary Completion: August 14, 2018
• Study Completion: February 1, 2020
• Last Updated: March 14, 2023

Record last verified: 2023-03

Locations

CA (1)