Impact of Metformin on Immuno-virologic Parameters in HIV

University of Hawaii

Status and phase

Unknown

Phase 3

Phase 2

Conditions

HIV/AIDS

Treatments

Drug: Metformin

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT04500678

H046

Details and patient eligibility

About

Non-diabetic, aviremic HIV-infected individuals on antiretroviral therapy (ART) will be randomized to metformin therapy or to observation for 72 weeks. Primary objective is to assess change over 72 weeks in CD4 T cell negative checkpoint receptors (PD-1 and TIGIT). As secondary objectives the study will look at 72 week change in other immuno-virologic parameters (CD8 T cell negative checkpoint receptors, plasma indoleamine 2,3-dioxygenase (IDO) levels and CD4 T cell and monocyte intracellular HIV DNA and HIV RNA. The study will also explore the 72 week impact of metformin on change in carotid intima-media thickness (cIMT) as a surrogate marker of atherosclerosis, on neuropsychological (NP) performance, strength, and change in body composition.

Enrollment

38 estimated patients

Sex

All

Ages

40+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

HIV+
On suppressive ART stable for > 1 year
Plasma HIV RNA < 50 copies/mL within 3 months of entry, with no HIV RNA > 200 copies/mL within the past 6 months prior to entry
Age >40 years
Ability and willingness to provide written informed consent

Exclusion criteria

Uncontrolled chronic medical condition or cancer
Acute illness within 2 weeks of entry
Diagnosis of diabetes by history, fasting blood glucose >126, or by HgbA1c > 6.5
Chronic, uncontrolled diarrhea
Known hypersensitivity or contraindication to metformin use
Current presence of hepatitis C including currently on or intent to start therapy for hepatitis C within the 48 week duration of study.
Serum B12 level below the reference normal range as listed by the commercial lab utilized for this study (Diagnostic Laboratory Services)
Pregnancy, or intent to become pregnant or nursing an infant
Any immunomodulator, HIV vaccine, any other vaccine, or investigational therapy within 30 days of study entry.
Current uncontrolled coronary artery disease or NYHA Class 3 or 4 congestive heart failure
History of liver cirrhosis
Current use of zidovudine, stavudine or didanosine
The following lab values
- Hemoglobin < 9.0 g/dL
- Absolute neutrophil count < 1000/μL
- Platelet count < 50,000/μL
- AST (SGOT) and ALT (SGPT) > 5x upper limit of normal (ULN)
- Calculated creatinine clearance (Cockcroft and Gault) < 50 ml/min
Active or recent past history (within past 2 years) of illicit substance or alcohol use or abuse which, in the judgment of the Investigator, will interfere with the patient's ability to comply with the protocol requirements
Patients, who, in the opinion of the Investigator, are unable to comply with the dosing schedule and protocol evaluation or for whom the study may not be advisable