A 72 Week, Randomized, Open-label vs Observation Study to Assess the Potential Immuno-virologic Benefit of Metformin in HIV-infected Individuals Receiving Antiretroviral Therapy
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 38
- 试验地点
- 1
- 主要终点
- CD4 T cell PD1+TIGIT+
研究概览
简要总结
Non-diabetic, aviremic HIV-infected individuals on antiretroviral therapy (ART) will be randomized to metformin therapy or to observation for 72 weeks. Primary objective is to assess change over 72 weeks in CD4 T cell negative checkpoint receptors (PD-1 and TIGIT). As secondary objectives the study will look at 72 week change in other immuno-virologic parameters (CD8 T cell negative checkpoint receptors, plasma indoleamine 2,3-dioxygenase (IDO) levels and CD4 T cell and monocyte intracellular HIV DNA and HIV RNA. The study will also explore the 72 week impact of metformin on change in carotid intima-media thickness (cIMT) as a surrogate marker of atherosclerosis, on neuropsychological (NP) performance, strength, and change in body composition.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •On suppressive ART stable for > 1 year
- •Plasma HIV RNA < 50 copies/mL within 3 months of entry, with no HIV RNA > 200 copies/mL within the past 6 months prior to entry
- •Age >40 years
- •Ability and willingness to provide written informed consent
排除标准
- •Uncontrolled chronic medical condition or cancer
- •Acute illness within 2 weeks of entry
- •Diagnosis of diabetes by history, fasting blood glucose >126, or by HgbA1c > 6.5
- •Chronic, uncontrolled diarrhea
- •Known hypersensitivity or contraindication to metformin use
- •Current presence of hepatitis C including currently on or intent to start therapy for hepatitis C within the 48 week duration of study.
- •Serum B12 level below the reference normal range as listed by the commercial lab utilized for this study (Diagnostic Laboratory Services)
- •Pregnancy, or intent to become pregnant or nursing an infant
- •Any immunomodulator, HIV vaccine, any other vaccine, or investigational therapy within 30 days of study entry.
- •Current uncontrolled coronary artery disease or NYHA Class 3 or 4 congestive heart failure
- •History of liver cirrhosis
- •Current use of zidovudine, stavudine or didanosine
- •The following lab values
- •Hemoglobin < 9.0 g/dL
- •Absolute neutrophil count < 1000/μL
- •Platelet count < 50,000/μL
- •AST (SGOT) and ALT (SGPT) > 5x upper limit of normal (ULN)
- •Calculated creatinine clearance (Cockcroft and Gault) < 50 ml/min
- •Active or recent past history (within past 2 years) of illicit substance or alcohol use or abuse which, in the judgment of the Investigator, will interfere with the patient's ability to comply with the protocol requirements
- •Patients, who, in the opinion of the Investigator, are unable to comply with the dosing schedule and protocol evaluation or for whom the study may not be advisable
研究组 & 干预措施
Metformin
Metformin 500 mg Extended Release (ER) qd increasing to 1000 mg ER qd at week 4 and continued to week 48.
干预措施: Metformin (Drug)
结局指标
主要结局
CD4 T cell PD1+TIGIT+
时间窗: Entry to week 72
Comparison of change over time in percentage of CD4 T cells bearing the PD1+TIGIT+ surface markers in peripheral blood mononuclear cells (PBMC) in the treatment (metformin) arm compared to the observation arm
次要结局
- Peripheral blood CD4 T cell intracellular HIV DNA(Entry to week 72)
- Peripheral blood monocyte intracellular HIV DNA(Entry to week 72)
- Peripheral blood monocyte intracellular HIV RNA(Entry to week 72)
- CD8 T cell PD1+TIGIT+(Entry to week 72)
- Plasma levels of indoleamine 2,3-dioxygenase (IDO)(Entry to week 72)
- Peripheral blood CD4 T cell intracellular HIV RNA(Entry to week 72)
研究者
Cecilia Shikuma
Professor, Medicine
University of Hawaii