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

The University of Alabama at Birmingham

Status and phase: Enrolling; Phase 4

Conditions: Systemic Inflammation; Immune Dysregulation; HIV; Injection Drug Use

Treatments: Drug: Metformin; Biological: Capvaxvie; Drug: Placebo; Biological: Jynneos

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT06829238

1R01DA060692-01A1 (U.S. NIH Grant/Contract)

000543853

Details and patient eligibility

About

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.

Full 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.

Enrollment: 100 estimated patients

Sex: All

Ages: 18 to 64 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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100 participants in 2 patient groups, including a placebo group

Metformin Group

Experimental group

Description:

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

Treatment:

Biological: Jynneos

Biological: Capvaxvie

Drug: Metformin

Placebo Group

Placebo Comparator group

Description:

Control Group

Treatment:

Biological: Jynneos

Biological: Capvaxvie

Drug: Placebo