Clinical trial NCT06829238: Assessment of Metformin for Restoration of Immune Homeostasis in HIV+ and HIV- Individuals With a History of Injection Drug Use
Official title: Assessment of Metformin for Restoration of Immune Homeostasis in HIV+ and HIV- Individuals With a History of Injection Drug Use (MET-IH)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Systemic Inflammation
Immune Dysregulation
Injection Drug Use
HIV
Keywords: Metformin
Immune restoration
Vaccine response
People who inject drugs (PWID)
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2025-02-17
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in Serum C-reactive Protein (CRP)
timeFrame: Baseline to Week 16
Secondary outcomes:
measure: Change in exhausted B cells
timeFrame: Baseline to Week 16
measure: Change in exhausted T cells
timeFrame: Baseline to Week 16
measure: Change in MPOX vaccine-specific IgG antibody.
timeFrame: Baseline to Week 13
measure: Change in PCV21 vaccine-specific IgG antibody.
timeFrame: Baseline to Week 9
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
Study officials:
References: