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

Purpose

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.

Condition

  • HIV

Eligibility

Eligible Ages
Between 40 Years and 65 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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 inhibitiors 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.

Study Design

Phase
N/A
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Eplerenone
Eplerenone 50 mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months
  • Drug: Eplerenone
    Eplerenone 50mg by mouth twice daily
  • Behavioral: Lifestyle Modification
    Counseling regarding diet and healthy activity
Placebo Comparator
Placebo
Placebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months
  • Drug: Placebo
    Placebo by mouth twice daily
  • Behavioral: Lifestyle Modification
    Counseling regarding diet and healthy activity

Recruiting Locations

Massachusetts General Hospital
Boston, Massachusetts 02114
Contact:
Suman Srinivasa, MD, MS
617-724-9109
ssrinivasa@mgh.harvard.edu

More Details

NCT ID
NCT02740179
Status
Recruiting
Sponsor
Massachusetts General Hospital

Study Contact

Suman Srinivasa, MD, MS
6177269109
ssrinivasa@mgh.harvard.edu

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.