Clinical trial NCT02740179: Effects of Eplerenone on Cardiovascular Disease in HIV (MIRACLE HIV Study)
Official title: Mineralocorticoid Receptor Antagonism for Cardiovascular Health in HIV--The MIRACLE HIV Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV
Keywords: Eplerenone
Cardiovascular Disease
Mineralocorticoid Receptor Antagonist
Coronary Vasculature
Myocardial Inflammation
Myocardial Fibrosis
Atherosclerosis
Aldosterone
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2016-04-15
Enrollment: 40
Sex: ALL
Minimum age (years): 40
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Myocardial Perfusion by PET
timeFrame: 12 Months
measure: Myocardial Perfusion by MRI
timeFrame: 12 Months
measure: Myocardial Inflammation
timeFrame: 12 Months
Secondary outcomes:
measure: Coronary Plaque
timeFrame: 12 Months
measure: Markers of Vascular Dysfunction
timeFrame: 12 Months
measure: Markers of Systemic Inflammation hsIL-6
timeFrame: 12 Months
measure: Markers of Systemic Inflammation hsCRP
timeFrame: 12 Months
measure: Markers of Immune Activation MCP-1
timeFrame: 12 Months
measure: Markers of Immune Activation sCD163
timeFrame: 12 Months
measure: Markers of Subclinical Injury
timeFrame: 12 Months
measure: Markers of Fibrosis
timeFrame: 12 Months
measure: Arterial Inflammation
timeFrame: 12 Months
measure: Markers of Arterial Inflammation
timeFrame: 12 Months
measure: Assessment of Cardiac Structure by Left Ventricular Mass on Cardiac Imaging
timeFrame: 12 Months
measure: Assessment of Cardiac Systolic Function Via Cardiac Imaging
timeFrame: 12 Months
measure: Assessment of Cardiac Diastolic Function Via Cardiac Imaging
timeFrame: 12 Months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
References:
citation: Srinivasa S, Fitch KV, Wong K, Torriani M, Mayhew C, Stanley T, Lo J, Adler GK, Grinspoon SK. RAAS Activation Is Associated With Visceral Adiposity and Insulin Resistance Among HIV-infected Patients. J Clin Endocrinol Metab. 2015 Aug;100(8):2873-82. doi: 10.1210/jc.2015-1461. Epub 2015 Jun 18.