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

Phase 4

Recruiting

• Conditions: Systemic Inflammation; Immune Dysregulation; Injection Drug Use; HIV
• Interventions: Drug: Metformin; Drug: Placebo; Biological: Jynneos; Biological: Capvaxvie

• Registration Number: NCT06829238
• Lead Sponsor: University of Alabama at Birmingham

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.

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 Timeline

• Study First Submitted: 2025-02-04
• Study First Submitted QC: 2025-02-10
• Study First Posted: 2025-02-17
• Status Verified: 2025-04
• Study Start: 2025-04-07
• Last Update Submitted: 2025-04-07
• Last Update Posted: 2025-04-09
• Primary Completion: 2028-11-30
• Study Completion: 2029-11-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Metformin Group	Metformin	Participants will receive Metformin ER (500mg increasing to 1000mg) for 16 weeks to assess immune restoration and inflammatory response.
Metformin Group	Jynneos	Participants will receive Metformin ER (500mg increasing to 1000mg) for 16 weeks to assess immune restoration and inflammatory response.
Metformin Group	Capvaxvie	Participants will receive Metformin ER (500mg increasing to 1000mg) for 16 weeks to assess immune restoration and inflammatory response.
Placebo Group	Placebo	Control Group
Placebo Group	Jynneos	Control Group
Placebo Group	Capvaxvie	Control Group

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States