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

NCT07007221 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: IDIM-2024-31723
• Study Type: interventional
• Target: 600
• Locations: 0 countries
• Sites: N/A

Brief 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

Outcome Measures

Primary Outcomes (1)

• MADRS Score

  A score indicating depression severity, ranging from 0-60 with a higher score indicating more severe depression

  8 weeks

Study Arms (8)

Part 1, group 1

EXPERIMENTAL

HIV patients with depression randomized to metformin dose 1000mg

Drug: Metformin

Part 1, group 2

EXPERIMENTAL

HIV patients with depression randomized to metformin dose 1500mg

Drug: Metformin

Part 2, group1

EXPERIMENTAL

HIV patients with depression randomized to metformin

Drug: Metformin

Part 2, group 2

PLACEBO COMPARATOR

HIV patients with depression randomized to placebo

Other: Placebo

Part 3, group 1

EXPERIMENTAL

HIV patients with depression randomized to Metformin

Drug: Metformin

Part 3, group 2

EXPERIMENTAL

HIV patients with depression randomized to fluoxetine

Drug: Fluoxetine

Part 3, group 3

EXPERIMENTAL

HIV patients with depression randomized to metformin + fluoxetine

Drug: Metformin+Fluoxetine

Part 3, group 4

EXPERIMENTAL

HIV patients with depression randomized to double placebo

Other: double placebo

Interventions

Metformin DRUG

12 weeks of Metformin 1000mg

Part 1, group 1

Placebo OTHER

8 weeks placebo drug

Part 2, group 2

Fluoxetine DRUG

12 weeks of Fluoxetine

Part 3, group 2

Metformin+Fluoxetine DRUG

12 weeks of Metformin+Fluoxetine

Part 3, group 3

double placebo OTHER

12 weeks of double placebo

Part 3, group 4

Eligibility Criteria

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

You may qualify if:

• years old
• HIV positive
• On HIV antiretroviral therapy for \> 6 months
• Undetectable HIV RNA
• Outpatient
• Depression by PHQ-9 \>10, confirmed by MADRS score 20+ and MINI interview
• Provision of Informed Consent
• Willingness to comply with all screening and study procedures
• Primary Residence \<50 km from clinic

You may not qualify if:

• Planning to move out of clinic catchment area in the next 3 months
• Suicidal (PHQ-9 question 9 score \>2) or MADRS item 10 with score of 4+
• Pregnant or breastfeeding
• Treatment with a rifamycin
• Current use of any antidepressant, metformin, rifampicin, efavirenz, insulin, or sulfonylurea.
• Active illicit drug use
• Bipolar or psychotic disorder
• Known cirrhosis or heart failure
• Glomerular Filtration Rate (GFR) \<45
• Abnormal TSH \>3.5 IU/mL
• Previous Enrollment in the trial (Parts 2 and 3)

Sponsors & Collaborators

• University of Minnesota: lead

MeSH Terms

Conditions

Depression; Acquired Immunodeficiency Syndrome

Interventions

Metformin; Fluoxetine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Propylamines; Amines

Study Officials

• Sarah Lofgren, MD

  University of Minnesota

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sarah Lofgren, MD

CONTACT

507-401-1624; lofg0020@umn.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a 3 part trial, parts 1 and 2 have 2 arms each, part 3 has 4 arms

Study Record Dates

• First Submitted: March 12, 2025
• First Posted: June 5, 2025
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2030
• Last Updated: January 14, 2026

Record last verified: 2026-01