Cardiometabolic Effects of Eplerenone in HIV Infection

June 21, 2018 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

HIV-infected individuals are at higher risk than uninfected people for developing cardiovascular disease. Visceral adipose tissue is also increased in HIV-infected people compared to uninfected individuals. Animal studies suggest that blockade of the mineralocorticoid receptor (MR) may have beneficial effects on cardiovascular and metabolic parameters via inhibition of adipocyte differentiation and triglyceride accumulation. We will examine the effects of the MR antagonist eplerenone (50 mg daily) on HIV-infected adults with abdominal fat accumulation in a 24-week, open-label, proof-of-concept study. Magnetic resonance imaging will be conducted at screening and the final study visit to evaluate cardiac and hepatic steatosis. We anticipate that blocking the effects of increased aldosterone secretion with eplerenone will significantly reduce intramyocardial lipid content and hepatic steatosis in this population. These effects may be accompanied by decreases in visceral adipose tissue, and improvements in dyslipidemia and inflammation, thereby improving cardiovascular health.

Study Type

Interventional

Enrollment (Actual)

5

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Institutes of Health Clinical Center, 9000 Rockville Pike

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment
Intervention: Eplerenone will be administered for 6 months as follows: 25 mg once daily for 1 week and then 50 mg once daily for the remainder of the study.
Drug: Inspra /Eplerenone
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Improvement of Cardiac Steatosis: Mean Change in Intraventricular Septum Percentage of Lipid by MR Spectroscopy.
Time Frame: 24 weeks
Mean change in intraventricular septum percentage of lipid by MR spectroscopy. This was calculated by subtracting the baseline intraventicular septum percentage value of lipid from the week 24 intraventicular septum percentage value of lipid by MR spectroscopy.
24 weeks
Improvement of Hepatic Steatosis: Mean Change in Hepatic Percentage of Lipid by MR Spectroscopy
Time Frame: 24 weeks
Mean change in hepatic percentage of lipid by MR spectroscopy. This was calculated by subtracting the baseline hepatic percentage value of lipid from the week 24 hepatic percentage value of lipid by MR spectroscopy.
24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

  • Principal Investigator: Colleen M Hadigan, M.D., National Institute of Allergy and Infectious Diseases (NIAID)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 2, 2015

Primary Completion (Actual)

September 11, 2017

Study Completion (Actual)

September 11, 2017

Study Registration Dates

First Submitted

December 10, 2015

First Submitted That Met QC Criteria

December 10, 2015

First Posted (Estimate)

December 14, 2015

Study Record Updates

Last Update Posted (Actual)

July 17, 2018

Last Update Submitted That Met QC Criteria

June 21, 2018

Last Verified

September 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 160030
  • 16-I-0030

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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