Inflammatory Pathogenesis of Coronary Atherosclerosis in HIV
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 81
- 试验地点
- 1
- 主要终点
- Coronary Endothelial Function Measured by Percent Change in Coronary Blood Flow With Exercise (%) at 8 Weeks
研究概览
简要总结
The investigators are studying whether an anti-inflammatory intervention improves impaired coronary endothelial function (CEF) in HIV+ people with no clinical coronary artery disease (CAD).
详细描述
Survival in people with HIV has significantly improved with the use of antiretroviral therapy (ART) but HIV+ people now experience an increasing burden of chronic diseases, including coronary atherosclerosis and coronary artery disease (CAD). HIV patients manifest an increased risk of CAD and its consequences possibly due to interplay of inflammation with traditional risk factors (smoking, high cholesterol, and poor diet), some of the latter accentuated by ART.
What the investigators are studying in this program is the function of the coronary arteries and in particular the inner lining of the arteries called the endothelium in patients with HIV. The endothelium has several important functions; one of them is that under conditions of stress it releases a substance called nitric oxide which increases the size of the artery and increases blood flow. When it is not functioning normally the artery does not increase as much and blood flow does not increase during stress.
The investigators study coronary artery function with magnetic resonance imaging, or MRI. MRI is a method of obtaining images of what is happening inside the body. MRI does not involve radiation, x-ray, or injection of contrast. The investigators can measure flow in the artery and the dimension of the artery at rest and with a handgrip stress and learn the extent to which the artery dilates and flow increases with the stress. The investigators believe that inflammation can interfere with normal function and that by decreasing inflammation abnormal endothelial function may be improved.
Colchicine is an anti-inflammatory agent approved by the Food and Drug Administration (FDA) to treat arthritis and some other conditions. This drug is not approved for use to suppress inflammation in patients with coronary artery disease and improve coronary artery endothelial function. The FDA is allowing the use of colchicine or a placebo in this research study.
This study will involve 24 weeks of colchicine or placebo and 3 Magnetic Resonance Imaging (MRI) scans of the heart and other study procedures.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 21 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients of either gender who are 21 years of age (no upper age limit), HIV positive and taking stable ART (no change in ART regimen in last 3 months),
- •HIV viral load <100 copies/mL (plasma HIV RNA concentration),
- •Abnormal CEF at baseline (<7ml/min change in CBF during IHE as compared to resting value).
排除标准
- •Patients unable to understand the risks, benefits, and alternatives of participation and give meaningful consent,
- •Patients with contraindications to MRI such as implanted metallic objects (pre-existing cardiac pacemakers, cerebral clips) or indwelling metallic projectiles,
- •History of clinical CAD, including acute coronary syndrome, myocardial infarction or revascularization,
- •Resting ECG with evidence of Q wave myocardial infarction,
- •Pregnant women,
- •Recent history, within the past 3 months, of cocaine or heroin use,
- •Moderate or greater renal impairment (estimated glomerular filtration rate <45ml/min),
- •Moderate-severe hepatic disease (elevation in hepatic transaminases >3x upper limit of normal),
- •Leukopenia (<3000/mm3) or thrombocytopenia (<100,000/mm3),
- •CD4<200 cell/mm3,
- •Chronic inflammatory condition such as lupus or rheumatoid arthritis, ulcerative colitis or Crohn's disease,
- •Requirement for, or intolerance to, colchicine,
- •Women of childbearing potential (even if using oral contraceptive agents) or intention to breastfeed,
- •Chronic, continuous use of oral or IV steroid therapy or other immunosuppressive or biologic response modifiers or anti-inflammatory agents (chronic NSAIDs or acetylsalicylic acid (ASA) >81mg daily),
- •History of chronic pericardial effusion, pleural effusion, ascites or peripheral neuropathy manifested by both signs and symptoms,
- •Taking protease inhibitors (PI), cobicistat, or CYP3A4 inhibitors.
研究组 & 干预措施
Colchicine
Colchicine 0.6 mg daily by mouth
干预措施: Colchicine (Drug)
Placebo
Placebo for colchicine 1 tablet by mouth daily
干预措施: Placebo (Drug)
结局指标
主要结局
Coronary Endothelial Function Measured by Percent Change in Coronary Blood Flow With Exercise (%) at 8 Weeks
时间窗: Difference between measurements at baseline compared to measurement at 8 weeks
Percent change in coronary blood flow (CBF) from rest to that during isometric handgrip exercise (IHE) stress at 8 weeks.
次要结局
- Change in Coronary Artery Cross-sectional Area (CSA) at 24 Weeks(At 24 weeks)
- High-sensitivity C-reactive Protein (hsCRP) at 8 Weeks.(At 8 weeks.)
- Change in Coronary Artery Cross-sectional Area (CSA) at 8 Weeks(Difference between measurements at baseline compared to measurement at 8 weeks)
- Coronary Endothelial Function at 24 Weeks;(At 24 weeks.)
- Brachial Flow Mediated Dilatation (FMD) at 24 Weeks.(At 24 weeks)
- Brachial Flow Mediated Dilatation (FMD) at 8 Weeks.(At 8 weeks)
- Interleukin-6 (IL-6) at 8 Weeks(At 8 weeks)
- High-sensitivity C-reactive Protein (hsCRP) at 24 Weeks(At 24 weeks)