Effects of Eplerenone on Cardiovascular Disease in HIV (MIRACLE HIV Study)

Massachusetts General Hospital40 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

HIV

Eligibility

Sex: ALLMin age: 40 YearsMax age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Ages 40-65 years 2. Antiretroviral use (ART) \>12 months and HIV viral load \<100 copies/mL 3. VAT\> 110cm2 Exclusion Criteria: 1. 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. 2. Unstable statin use \<12 months. Stable use (\>12 months) is allowed. 3. Use of full dose ritonavir, nelfinavir, clarithromycin, and other strong inhibitors of CYP3A4, as well as CYP3A4 inducers. 4. Continuous oral steroid use (equivalent to prednisone \> 5 mg daily) within the last 3 months. 5. Uncontrolled diabetes requiring insulin and/or HbA1c \> 7.5%. 6. Creatinine (Cr) \> 1.5 mg/dL or estimated GFR\<60 mL/min/1.73m2. 7. K \> 5.5 mEq/L. 8. Hemoglobin \< 10 g/dL. 9. Known liver disease or ALT \>3x ULN. 10. History of congestive heart failure, stroke, myocardial infarction, or known coronary artery disease. 11. Pregnant, actively seeking pregnancy or breastfeeding. 12. Estrogen, progestin derivative, or other sex steroid use within last 3 months. Stable physiologic testosterone replacement (\> 3 months) is acceptable. 13. Current bacterial or other infections. 14. Active substance abuse. 15. 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. 16. Previous reaction or contraindication to iodine-containing contrast media and gadolinium. 17. Coronary artery luminal narrowing \>70% on coronary CTA.

Outcomes

Primary Outcomes

Myocardial Perfusion by PET

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.

Time frame: 12 Months

Myocardial Perfusion by MRI

Change (value at 12 months minus value at baseline) in myocardial perfusion assessed by myocardial blood flow measured via cardiac magnetic resonance imaging

Time frame: 12 Months

Myocardial Inflammation

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

Time frame: 12 Months

Secondary Outcomes

Coronary Plaque

Change (value at 12 months minus value at baseline) in coronary plaque measured via coronary computed tomography angiogram assessed by coronary calcium score Scale: minimum 0 to maximum no limit, higher score indicates more plaque

Time frame: 12 Months

Markers of Vascular Dysfunction

Change (value at 12 months minus value at baseline) in serum hs-cTnT

Time frame: 12 Months

Markers of Systemic Inflammation hsIL-6

Change (value at 12 months minus value at baseline) in plasma hsIL-6

Time frame: 12 Months

Markers of Systemic Inflammation hsCRP

Change (value at 12 months minus value at baseline) in plasma hsCRP

Time frame: 12 Months

Markers of Immune Activation MCP-1

Change (value at 12 months minus value at baseline) in plasma MCP-1

Time frame: 12 Months

Markers of Immune Activation sCD163

Change (value at 12 months minus value at baseline) in plasma sCD163

Time frame: 12 Months

Markers of Subclinical Injury

Change (value at 12 months minus value at baseline) in serum NT-proBNP

Time frame: 12 Months

Markers of Fibrosis

Change (value at 12 months minus value at baseline) in myocardial fibrosis measured by T1 (a signal intensity that measures fibrosis) via cardiac magnetic resonance imaging

Time frame: 12 Months

Arterial Inflammation

Percentage change (value at 12 months minus value at baseline) in target to background ratio (a measure of arterial inflammation) of the index vessel measured via positron emission tomography/computed tomography

Time frame: 12 Months

Markers of Arterial Inflammation

Change (value at 12 months minus value at baseline) in plasma LpPLA2

Time frame: 12 Months

Assessment of Cardiac Structure by Left Ventricular Mass on Cardiac Imaging

Change (value at 12 months minus value at baseline) in left ventricular mass on cardiac magnetic resonance imaging

Time frame: 12 Months

Assessment of Cardiac Systolic Function Via Cardiac Imaging

Change (value at 12 months minus value at baseline) in global circumferential strain (GCS) on cardiac magnetic resonance imaging

Time frame: 12 Months

Assessment of Cardiac Diastolic Function Via Cardiac Imaging

Change (value at 12 months minus value at baseline) in left ventricular end diastolic volume on cardiac magnetic resonance imaging

Time frame: 12 Months

Effects of Eplerenone on Cardiovascular Disease in HIV (MIRACLE HIV Study)

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes