Assessment of Metformin for Restoration of Immune Homeostasis in HIV+ and HIV- Individuals with a History of Injection Drug Use
Purpose
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
Eligibility
- Eligible Ages
- Between 18 Years and 64 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
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
- Phase
- Phase 4
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- Single (Participant)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
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 |
|
Recruiting Locations
University of Alabama at Birmingham
Birmingham, Alabama 35294
Birmingham, Alabama 35294
More Details
- Status
- Recruiting
- Sponsor
- University of Alabama at Birmingham
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.