Recruiting

Metformin

Sponsor:

University of Alabama at Birmingham

Code:

NCT06829238

Conditions

Systemic Inflammation

Immune Dysregulation

Injection Drug Use

HIV

Eligibility Criteria

Sex: All

Age: 18 - 64

Healthy Volunteers: Not accepted

Interventions

Metformin

Placebo

Jynneos

Capvaxvie

Study Details

Brief summary:

This randomized clinical trial (RCT) evaluates whether metformin can reduce systemic inflammation and improve immune function in individuals with a history of injection drug use, with or without HIV. Participants will receive metformin or placebo and undergo immune system assessments, including vaccine response evaluations.

Conditions

Systemic Inflammation

Immune Dysregulation

Injection Drug Use

HIV

Study ID

NCT06829238

Start date

Apr 7, 2025

Status verified date

Apr, 2026

Completion date

Nov 30, 2029

Anticipated

Primary completion date

Nov 30, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 64

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Provision of signed and dated informed consent.
  • Stated willingness to comply with all study procedures and availability for the study duration.
  • Aged 18 to 64 years old.
  • Weight of at least 110 lbs.
  • Body Mass Index (BMI) of 18.5-40. Enrollment of individuals with BMI >40, deemed in good health, may be considered with approval.
  • Willingness to receive Jynneos (MPOX) and Capvaxvie vaccines.
  • Ability to take oral medication and willingness to adhere to the metformin treatment regimen.
  • History of injection opioid, amphetamine, and/or cocaine use within the past 10 years (self-report).
  • Use of non-prescription opioid, amphetamine, and/or cocaine within the past 30 days (self-report).
  • Clinically confirmed urine drug screen for opioid, amphetamine, and/or cocaine within the past 30 days.
  • Serum CRP > 3 mg/dL.
  • Glucose level between 70-180 mg/dL (non-fasting).
  • Hemoglobin A1c (HbA1c) of 5.0-6.4%.
  • CD4 count > 200 cells/ml.
  • If HIV-positive, HIV viral load < 200 copies/ml.
  • If HIV-positive, on anti-retroviral therapy (ART) for >12 months.

Exclusion Criteria:

  • Inability to give informed consent.
  • Refusal or inability to have blood drawn.
  • Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy, platelet disorder requiring precautions).
  • Pregnant or nursing individuals.
  • Diabetes mellitus.
  • History of severe renal impairment or eGFR <60 mL/min/1.73m².
  • Creatinine clearance <60 mL/min.
  • History of liver disease.
  • ALT/AST > 3× the upper limit of normal.
  • Total bilirubin >1.4 mg/dL.
  • Albumin <3.5 g/dL.
  • Prothrombin >1.5× the upper limit of normal.
  • AUDIT-C score ≥8.
  • Hemoglobin <9.0 g/L.
  • Absolute neutrophil count <1,000/mL.
  • Platelet count <100,000/mL.
  • History of acute or chronic metabolic acidosis.
  • Serum bicarbonate <22 mEq/L.
  • Anion gap >10 mEq/L.
  • Serum lactate >2.2 mmol/L.
  • Serum vitamin B12 <250 pg/mL.
  • History of chronic diarrhea.
  • Current use of metformin or other diabetes medications.
  • History of myocardial infarction, endocarditis, stroke, heart failure, chronic obstructive pulmonary disease, or sepsis.
  • Use of medications such as furosemide, nifedipine, ranolazine, vandetanib, or cimetidine (current or within the past 30 days).
  • Active hepatitis B infection.
  • Hepatitis C infection within 6 months of study entry; individuals with prior hepatitis C must be at least 6 months post-treatment with direct-acting antivirals.
  • Previous receipt of Jynneos or pneumococcal vaccine within the past two years (self-report).
  • Severe allergic reaction to metformin, Jynneos, or Capvaxvie (self-report). Blood donations exceeding 450 mL in the 8 weeks prior to enrollment, accounting for study-related blood draws.
  • Any medical, psychiatric, social condition, or responsibility that, in the investigator's judgment, could interfere with study procedures.

Study Design

Enrollment

100 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Metformin Group

Participants will receive Metformin ER (500mg increasing to 1000mg) for 16 weeks to assess immune restoration and inflammatory response.

placebo comparator: Placebo Group

Control Group

Interventions

Metformin

Participants will receive Metformin ER (500mg increasing to 1000mg) or placebo for 16 weeks to assess immune restoration and inflammatory response.

Placebo

Participants will receive placebo for 16 weeks and assess immune restoration and inflammatory response.

Jynneos

All participants will take a Jynneos (MPOX) vaccine.

Capvaxvie

All participants will take a Capvaxvie (PCV21, pneumococcal) vaccine.

Primary outcome measure

  • Change in Serum C-reactive Protein (CRP) [ Time Frame: Baseline to Week 16 ]

Central Contacts and Locations

Central contacts

Ellen Eaton, MD, MSPH

205-975-0661eeaton@uabmc.edu

James Kobie, PhD

205-934-8800jjkobie@uabmc.edu

Locations

University of Alabama at Birmingham

Recruiting

Birmingham, Alabama, United States, 35294

Contacts

Ellen Eaton, MD, MSPH

205-975-0661eeaton@uabmc.edu

James Kobie, PhD

jjkobie@uabmc.edu

More Information

Sponsor

University of Alabama at Birmingham

Last update posted

Apr 22, 2026

Last verified

Apr, 2026

Keywords

  • Metformin
  • Immune restoration
  • Vaccine response
  • People who inject drugs (PWID)

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University of Alabama at Birmingham on 2026-04-22.