Clinical trial NCT07007221: Clinical Trials to Evaluate Metformin to Treat Depression in People Living With HIV
Official title: Clinical Trials to Evaluate Metformin to Treat Depression in People Living With HIV
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Depression
Hiv
Lead sponsor: University of Minnesota
Sponsor class: OTHER
First posted: 2025-06-05
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a 3 part trial, parts 1 and 2 have 2 arms each, part 3 has 4 arms
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 18-65 years old
* HIV positive
* On HIV antiretroviral therapy for \&gt; 6 months
* Undetectable HIV RNA
* Outpatient
* Depression by PHQ-9 \&gt;10, confirmed by MADRS score 20+ and MINI interview
* Provision of Informed Consent
* Willingness to comply with all screening and study procedures
* Primary Residence \&lt;50 km from clinic

Exclusion Criteria:

* Planning to move out of clinic catchment area in the next 3 months
* Suicidal (PHQ-9 question 9 score \&gt;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) \&lt;45
* Abnormal TSH \&gt;3.5 IU/mL
* Previous Enrollment in the trial (Parts 2 and 3)

Primary outcomes:
measure: MADRS Score
timeFrame: 8 weeks
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: University of Minnesota
name: Sarah Lofgren, MD
role: PRINCIPAL_INVESTIGATOR
References: