Clinical Trials to Evaluate Metformin to Treat Depression in People Living With HIV

Summary

Depression in HIV occurs commonly and causes poor HIV outcomes with public health implications.

Depression prevalence in HIV-infected persons is estimated at 26% compared to 5% in the general population. Adherence to antiretroviral medication is a life-saving treatment in HIV, but depression can reduce engagement in care and adherence to medication. Depression is also associated with poorer levels of viral suppression and even mortality. Overall, those with depression and HIV are less likely to return to health and remain more likely to transmit the virus. therefore, treatment of HIV is essential to prevention; lower engagement in and adherence to HIV treatment due to depression puts others at risk. This is a 3 part trial, an initial pilot, a placebo controlled pilot, and a full trial.

Part 1. Dose response, Tolerability/Acceptability of Metformin for Depression in people with HIV: To do Initial assessment of metformin for depression in people with HIV we will perform a randomized, double blind, 2-arm, 12 week randomized controlled trial to assess feasibility and acceptability of metformin for depression. We will test two doses of metformin 1000 mg daily versus 1500 mg daily.

Part 2. Preliminary Efficacy Trial of Metformin for Depression in People with HIV: This will be a two-arm, double-blind trial of metformin versus placebo in people with HIV and depression. We will randomize individuals 1:1 to metformin or placebo. Will then collect blood and rectal swabs for preliminary assessments of the mechanism of action for metformin in people with HIV and depression.

Part 3. Full efficacy factorial trial of metformin for depression and comparison/interaction with fluoxetine in people living with HIV: To assess metformin and fluoxetine as efficacious treatments for depression in people with HIV, we will conduct a 4-arm, 12-week, mechanistic, double-blinded, randomized controlled treatment trial (RCT) with an assessment of inflammation and the gut microbiome. Participants (n=400) will be HIV- positive patients on ART with comorbid depression receiving care at one of two Ugandan clinics. In addition, we will use the NIMH Research Domain Criteria (RDoC) of Acute Threat and loss under Negative Valence using biomarkers and self-reported tools.

Conditions

• Depression
• Hiv

Interventions

DRUG

Metformin

12 weeks of Metformin 1000mg

DRUG

Metformin

12 weeks of Metformin 1500mg

DRUG

Metformin

8 weeks of Metformin

OTHER

Placebo

8 weeks placebo drug

DRUG

Metformin

12 weeks of Metformin

DRUG

Fluoxetine

12 weeks of Fluoxetine

DRUG

Metformin+Fluoxetine

12 weeks of Metformin+Fluoxetine

OTHER

double placebo

12 weeks of double placebo

Sponsors & Collaborators

• University of Minnesota

  lead OTHER

Principal Investigators

• Sarah Lofgren, MD · University of Minnesota

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-07-01

Primary Completion

2030-12-01

Completion

2030-12-01

FDA Drug

Yes