Mineralocorticoid Receptor Antagonism for Cardiovascular Health in HIV--The MIRACLE HIV Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Myocardial Perfusion by PET
研究概览
简要总结
HIV-infected individuals treated with antiretroviral medications are living longer, but have an increased risk of heart disease when compared to non-HIV-infected individuals. A hormone called aldosterone, which regulates blood pressure and sodium balance, is elevated in the HIV population in association with with increased belly fat and altered glucose metabolism. Elevations in aldosterone hormone may also be associated with abnormal blood flow, inflammation, and coronary plaque in the heart. This study is being conducted to evaluate whether therapies to reduce the actions of aldosterone may decrease the burden and progression of heart disease in the HIV population.
详细描述
This is a 12 month randomized, placebo controlled study enrolling HIV-infected individuals with no known history of cardiovascular disease. Eplerenone is a mineralocorticoid receptor antagonist, which can block aldosterone activation. This medication is approved by the FDA for high blood pressure and heart failure. This study aims to investigate the effect of eplerenone on other measures of cardiovascular disease in HIV. Using PET, MRI, and CT imaging technology, this study will evaluate whether eplerenone can improve coronary flow reserve and myocardial inflammation/fibrosis, in addition to atherosclerotic plaque build-up among the HIV population. The study also includes teaching on lifestyle modification to promote a healthy diet and exercise program.There are 3 overnight visits in addition to safety visits.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ages 40-65 years
- •Antiretroviral use (ART) >12 months and HIV viral load <100 copies/mL
- •VAT> 110cm2
排除标准
- •Antihypertensive use including, ACE Inhibitor, ARB, MR blockade, diuretic, potassium (K) supplementation; or BP>140/90 mmHg. Stable use (>3 months) of beta-blockers or calcium channel blockers (CCB) (except verapamil) is allowed.
- •Unstable statin use <12 months. Stable use (>12 months) is allowed.
- •Use of full dose ritonavir, nelfinavir, clarithromycin, and other strong inhibitors of CYP3A4, as well as CYP3A4 inducers.
- •Continuous oral steroid use (equivalent to prednisone > 5 mg daily) within the last 3 months.
- •Uncontrolled diabetes requiring insulin and/or HbA1c > 7.5%.
- •Creatinine (Cr) > 1.5 mg/dL or estimated GFR<60 mL/min/1.73m
- •K > 5.5 mEq/L.
- •Hemoglobin < 10 g/dL.
- •Known liver disease or ALT >3x ULN.
- •History of congestive heart failure, stroke, myocardial infarction, or known coronary artery disease.
- •Pregnant, actively seeking pregnancy or breastfeeding.
- •Estrogen, progestin derivative, or other sex steroid use within last 3 months. Stable physiologic testosterone replacement (> 3 months) is acceptable.
- •Current bacterial or other infections.
- •Active substance abuse.
- •Significant radiation exposure over the course of the year prior to randomization (e.g., radiation therapy, PCI, catheter ablation of arrhythmia) within 12 months of randomization.
- •Previous reaction or contraindication to iodine-containing contrast media and gadolinium.
- •Coronary artery luminal narrowing >70% on coronary CTA.
研究组 & 干预措施
Eplerenone
Eplerenone 50 mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months
干预措施: Eplerenone (Drug)
Eplerenone
Eplerenone 50 mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months
干预措施: Lifestyle Modification (Behavioral)
Placebo
Placebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months
干预措施: Placebo (Drug)
Placebo
Placebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months
干预措施: Lifestyle Modification (Behavioral)
结局指标
主要结局
Myocardial Perfusion by PET
时间窗: 12 Months
Change (value at 12 months minus value at baseline) in myocardial perfusion assessed by coronary flow reserve measured via cardiac positron emission tomography. Coronary flow reserve is given by the ratio of blood flow at stress during maximal dilation of the coronary arteries to blood flow at rest.
Myocardial Perfusion by MRI
时间窗: 12 Months
Change (value at 12 months minus value at baseline) in myocardial perfusion assessed by myocardial blood flow measured via cardiac magnetic resonance imaging
Myocardial Inflammation
时间窗: 12 Months
Change (value at 12 months minus value at baseline) in myocardial inflammation measured by extracellular mass index (a measure of the inflammation within the heart) via cardiac magnetic resonance imaging
次要结局
- Markers of Vascular Dysfunction(12 Months)
- Coronary Plaque(12 Months)
- Markers of Systemic Inflammation hsCRP(12 Months)
- Markers of Systemic Inflammation hsIL-6(12 Months)
- Markers of Immune Activation MCP-1(12 Months)
- Markers of Immune Activation sCD163(12 Months)
- Markers of Subclinical Injury(12 Months)
- Markers of Fibrosis(12 Months)
- Arterial Inflammation(12 Months)
- Markers of Arterial Inflammation(12 Months)
- Assessment of Cardiac Structure by Left Ventricular Mass on Cardiac Imaging(12 Months)
- Assessment of Cardiac Systolic Function Via Cardiac Imaging(12 Months)
- Assessment of Cardiac Diastolic Function Via Cardiac Imaging(12 Months)
研究者
Steven K. Grinspoon, MD
Professor of Medicine
Massachusetts General Hospital