Assessment of Metformin for Restoration of Immune Homeostasis in HIV+ and HIV- Individuals With a History of Injection Drug Use (MET-IH)
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 2
- 主要终点
- Change in Serum C-reactive Protein (CRP)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 64 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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-
- •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.
排除标准
- •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 ≥
- •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.
研究组 & 干预措施
Placebo Group
Control Group
干预措施: Jynneos (Biological)
Placebo Group
Control Group
干预措施: Capvaxvie (Biological)
Metformin Group
Participants will receive Metformin ER (500mg increasing to 1000mg) for 16 weeks to assess immune restoration and inflammatory response.
干预措施: Jynneos (Biological)
Metformin Group
Participants will receive Metformin ER (500mg increasing to 1000mg) for 16 weeks to assess immune restoration and inflammatory response.
干预措施: Capvaxvie (Biological)
Placebo Group
Control Group
干预措施: Placebo (Drug)
Metformin Group
Participants will receive Metformin ER (500mg increasing to 1000mg) for 16 weeks to assess immune restoration and inflammatory response.
干预措施: Metformin (Drug)
结局指标
主要结局
Change in Serum C-reactive Protein (CRP)
时间窗: 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.
次要结局
- Change in exhausted B cells(Baseline to Week 16)
- Change in exhausted T cells(Baseline to Week 16)
- Change in MPOX vaccine-specific IgG antibody.(Baseline to Week 13)
- Change in PCV21 vaccine-specific IgG antibody.(Baseline to Week 9)
研究者
Ellen Eaton
Dr. Ellen Eaton
University of Alabama at Birmingham