Cardiometabolic Effects of Eplerenone in HIV Infection
Condition: Cardiac Steatosis; Hepatic Steatosis
MeSH terms: HIV Infections; Fatty Liver
Intervention: Inspra /Eplerenone
Intervention description: Eplerenone is provided as 25- or 50-mg tablets that are to be taken orally. Subjects will be dosed at 25 mg daily for 1 week, and then 50 mg daily for 23 weeks. The total duration of dosing for each subject is 24 weeks.
Intervention MeSH terms: Eplerenone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 5.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Hepatic Steatosis; Cardiac Steatosis; Aldosterone; Eplerenone; Mineralcorticoid Receptor

Summary:

      Background:

      People with human immunodeficiency virus (HIV) are at a high risk of getting visceral or deep
      belly fat. Visceral fat can cause health problems like heart or liver disease. Researchers
      want to see if a blood pressure drug can help by blocking a hormone in the body.

      Objective:

      To see if eplerenone reduces fat stored in the heart muscle and liver in people with HIV and
      increased visceral fat.

      Eligibility:

      Adults ages 18 75 with HIV and increased waist circumference. Increased waist circumference
      is defined as more than 40 inches in men and more than 35 inches in women.

      Design:

      Participants will be screened with:

      Physical exam

      Medical history

      Blood tests

      Measurements of hips, waist, legs, arms, shoulders, and neck

      Magnetic resonance imaging (MRI) scan. They will lie on a table that slides into a machine.

      Electrocardiogram (EKG) to measure heart electrical activity

      Transient elastography, a special ultrasound to measure liver tissue stiffness

      A small piece their liver collected (optional)

      Participants will have a baseline visit:

      Physical exam

      Medical history

      Blood tests

      DEXA scan to measure body fat, muscle mass, and bone density. Participants will lie on a
      table while a very small dose of x-rays goes through the body.

      Resting energy expenditure (REE). This measures the amount of oxygen breathed in and carbon
      dioxide breathed out.

      Participants will get a 1-week supply of eplerenone. They will take one pill per day.

      Participants will have a follow-up visit 1 week later. They will have:

      Physical exam

      Medical history

      Blood tests

      23-week supply of eplerenone

      Participants will have 5 more follow-up visits.

      Participants will have a final study visit, repeating many of the screening and baseline
      tests.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

               1. Increased waist circumference on the basis of National Cholesterol Education
                  Program guidelines (> 102 cm in men and > 88 cm in women)

               2. Hepatic steatosis established by hepatic MRI greater than or equal to 5% and/or
                  liver biopsy within the last 12 months

               3. HIV-infected, HIV viral load < 50 copies/mL and no change in ART regimen for at
                  least 3 months

               4. Age greater than or equal to 18 and less than or equal to 75 years

               5. Agree to have samples stored for future research

        EXCLUSION CRITERIA:

          1. Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m^2, serum creatinine >
             1.5 mg/dL

          2. Serum potassium > 5.5 mEq/L, alanine aminotransferase > 2.5 times the upper limit of
             normal, hemoglobin (Hgb) < 11 g/dL

          3. Uncontrolled hypertension: systolic blood pressure greater than or equal to 160 mm Hg
             or diastolic blood pressure greater than or equal to 100 mm Hg

          4. A blood pressure < 90mmHg systolic or < 50mm Hg diastolic

          5. Screening EKG with a significant heart block (e.g. PR > 300 ms) or an EKG determined
             significant by Cardiology consult.

          6. Current hepatitis C infection, unless there has been a sustained virologic response
             for at least 12 months

          7. Type 2 diabetes with microalbuminuria

          8. Current or prior steroid use within past 6 months (except short-course or single-dose
             administration). Stable use of inhaled or nasal steroids are allowed.

          9. Use of angiotensin converting enzyme (ACE) inhibitors, angiotensin reporter blockers
             (ARBs), potassium-sparing diuretics, and other medications that may increase the risk
             of hyperkalemia

         10. Use of potassium supplementation or other medications known to increase potassium

         11. Concomitant use of strong inhibitors and/or inducers ofof cytochrome P450 isozyme
             (CYP)3A4

         12. If receiving testerone, estrogen or progesterone therapy, must be on a stable dose for
             at least 3 months.

         13. Current use of growth hormone or growth hormone-releasing hormone

         14. Current serious viral, bacterial, or other infection (excluding HIV)

         15. Current active substance abuse/dependence

         16. Substantial history of cardiovascular disease, including prior myocardial infarction
             (MI), congestive heart failure, or stroke

         17. Contraindication to MRI

         18. Pregnant or planning to become pregnant

         19. Breastfeeding

         20. Any condition that, in the opinion of the PI, may substantially increase the risk of
             participation