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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Metformin
  Participants will receive Metformin ER (500mg increasing to 1000mg) or placebo for 16 weeks to assess immune restoration and inflammatory response.
• Препарат Placebo
  Participants will receive placebo for 16 weeks and assess immune restoration and inflammatory response.
• Биопрепарат Jynneos
  All participants will take a Jynneos (MPOX) vaccine.
• Биопрепарат Capvaxvie
  All participants will take a Capvaxvie (PCV21, pneumococcal) vaccine.

Первичные конечные точки

• Change in Serum C-reactive Protein (CRP) [Срок оценки: Baseline to Week 16]

Вторичные конечные точки (4)

• Change in exhausted B cells [Срок оценки: Baseline to Week 16]
• Change in exhausted T cells [Срок оценки: Baseline to Week 16]
• Change in MPOX vaccine-specific IgG antibody. [Срок оценки: Baseline to Week 13]
• Change in PCV21 vaccine-specific IgG antibody. [Срок оценки: Baseline to Week 9]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• University of Alabama at Birmingham — Birmingham

Идентификаторы

NCT: NCT06829238 · 000543853 · 1R01DA060692-01A1

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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