A 72 Week, Randomized, Open-label vs Observation Study to Assess the Potential Immuno-virologic Benefit of Metformin in HIV-infected Individuals Receiving Antiretroviral Therapy
| Registry | NCT04500678 |
|---|---|
| Status | Terminated - During the COVID pandemic, our IRB halted enrollment into the study among other changes. Post COVID it was decided that too long an interval between patient enrollment was problematic for the study and a discussion was made to terminate. |
| Phase | Phase 2 / Phase 3 |
| Study type | Interventional; randomized, parallel, masking: double, diagnostic |
| Enrollment | 29 (Actual) |
| Sponsor | University of Hawaii (Other); collaborators: Merck Sharp & Dohme LLC |
| Conditions | HIV/AIDS |
| Interventions | Metformin (Drug) |
| Dates | start 2019-02-01, primary completion 2022-02-01, completion 2022-12-31, first posted 2020-08-05, last updated 2026-10-20 |
| Locations | 1 site in United States |
Related Papers Related Patents Related Grants Related Experts
All trials for HIV/AIDS All trials of Metformin
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). 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.
| Arm | Type | Interventions | Description |
|---|---|---|---|
| Metformin | Experimental | Drug: Metformin | Metformin 500 mg Extended Release (ER) qd increasing to 1000 mg ER qd at week 4 and continued to week 48. |
| Observation | No intervention | Observed without metformin |
Sex: All, ages: 40 Years to any
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
| Milestone | Metformin | Observation |
|---|---|---|
| Started | 14 | 15 |
| Completed | 7 | 11 |
| Not completed | 7 | 4 |
Time frame: from enrollment until end of follow-up, up to 72 weeks
| Arm | Deaths | Serious adverse events | Other adverse events |
|---|---|---|---|
| Metformin | 0/14 (0.0%) | 0/14 (0.0%) | 4/14 (28.6%) |
| Observation | 0/15 (0.0%) | 0/15 (0.0%) | 1/15 (6.7%) |
| Term | Organ system | Metformin | Observation |
|---|---|---|---|
| Gastrointestinal Symptoms | Gastrointestinal disorders | 4/14 | 1/15 |
Limitations and caveats: The study was halted due to the impact of the COVID pandemic. The total number of evaluable participants was very small limiting our ability to analyze. Also, while participants already on the study continued to be followed during the pandemic, immunologic changes due to COVID may also have interfered with the results of the primary analysis.
| Facility | City | Country | Status |
|---|---|---|---|
| John A. Burns School of Medicine, University of Hawaii - Manoa | Honolulu, Hawaii | United States |