Assessment of Metformin for Restoration of Immune Homeostasis in HIV+ and HIV- Individuals With a History of Injection Drug Use ((MET-IH))

Assessment of Metformin for Restoration of Immune Homeostasis in HIV+ and HIV- Individuals With a History of Injection Drug Use (MET-IH)

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.

Study Overview

• Status: Recruiting
• Conditions: HIV; Immune Dysregulation; Systemic Inflammation; Injection Drug Use
• Intervention / Treatment: Drug: Metformin; Biological: Jynneos; Biological: Capvaxvie; Drug: Placebo

Detailed Description

The study aims to assess the impact of metformin on immune dysregulation among 100 adults (ages 18-64) with a history of injection drug use. Participants will be randomized 1:1 to metformin (500mg increasing to 1000mg) or placebo for 16 weeks, during which they will receive Jynneos (MPOX) and Capvaxvie (PCV21, pneumococcal) vaccines. Immunologic responses will be monitored over 6 months post-enrollment.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Ellen Eaton, MD, MSPH; Phone Number: 205-975-0661; Email: eeaton@uabmc.edu
• Study Contact Backup: Name: James Kobie, PhD; Phone Number: 205-934-8800; Email: jjkobie@uabmc.edu

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Recruiting
      • University of Alabama at Birmingham
      • Contact: Ellen Eaton, MD, MSPH; Phone Number: 205-975-0661; Email: eeaton@uabmc.edu
      • Contact: James Kobie, PhD; Email: jjkobie@uabmc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Metformin Group; Participants will receive Metformin ER (500mg increasing to 1000mg) for 16 weeks to assess immune restoration and inflammatory response.	Drug: Metformin; Participants will receive Metformin ER (500mg increasing to 1000mg) or placebo for 16 weeks to assess immune restoration and inflammatory response.; Biological: Jynneos; All participants will take a Jynneos (MPOX) vaccine.; Biological: Capvaxvie; All participants will take a Capvaxvie (PCV21, pneumococcal) vaccine.
Placebo Comparator: Placebo Group; Control Group	Biological: Jynneos; All participants will take a Jynneos (MPOX) vaccine.; Biological: Capvaxvie; All participants will take a Capvaxvie (PCV21, pneumococcal) vaccine.; Drug: Placebo; Participants will receive placebo for 16 weeks and assess immune restoration and inflammatory response.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Serum C-reactive Protein (CRP)	Assessed by Enzyme Linked Immunosorbent Assay (ELISA) of blood samples collected at baseline and at 16 weeks. Reported in mg/dL.	Baseline to Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in exhausted B cells	Assessed by flow cytometry of blood samples collected at baseline and at 16 weeks. Reported as percentage of total B cells.	Baseline to Week 16
Change in exhausted T cells	Assessed by flow cytometry of blood samples collected at baseline and at 16 weeks. Reported as percentage of total T cells.	Baseline to Week 16
Change in MPOX vaccine-specific IgG antibody.	Assessed by Enzyme Linked Immunosorbent Assay (ELISA) of blood samples collected at baseline and at 13 weeks. Reported as micrograms/mL.	Baseline to Week 13
Change in PCV21 vaccine-specific IgG antibody.	Assessed by Enzyme Linked Immunosorbent Assay (ELISA) of blood samples collected at baseline and at 9 weeks. Reported as micrograms/mL.	Baseline to Week 9

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Collaborators: National Institute on Drug Abuse (NIDA)

Study record dates

Study Major Dates

• Study Start (Actual): April 7, 2025
• Primary Completion (Estimated): November 30, 2028
• Study Completion (Estimated): November 30, 2029

Study Registration Dates

• First Submitted: February 4, 2025
• First Submitted That Met QC Criteria: February 10, 2025
• First Posted (Actual): February 17, 2025

Study Record Updates

• Last Update Posted (Actual): April 22, 2026
• Last Update Submitted That Met QC Criteria: April 17, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: People who inject drugs (PWID); Metformin; Immune restoration; Vaccine response
• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation; Organic Chemicals; Biguanides; Guanidines; Amidines; Metformin; smallpox and monkeypox vaccine modified vaccinia ankara-bavarian nordic
• Other Study ID Numbers: 000543853; 1R01DA060692-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No