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Cardiometabolic Effects of Eplerenone in HIV Infection

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ClinicalTrials.gov Identifier: NCT02629094
Recruitment Status : Terminated
First Posted : December 14, 2015
Results First Posted : July 17, 2018
Last Update Posted : July 17, 2018
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )

Tracking Information
First Submitted Date  ICMJE December 10, 2015
First Posted Date  ICMJE December 14, 2015
Results First Submitted Date  ICMJE May 7, 2018
Results First Posted Date  ICMJE July 17, 2018
Last Update Posted Date July 17, 2018
Study Start Date  ICMJE December 2, 2015
Actual Primary Completion Date September 11, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 21, 2018)
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: December 10, 2015)
  • Improvement of cardiac steatosis as measured by MRI of the intraventricular septum [ Time Frame: 7 months ]
  • Improvement of hepatic steatosis as measured by MRI of the liver and histopathologic examination of liver biopsy [ Time Frame: 7 months ]
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: December 10, 2015)
Reduction of biomarkers of inflammation and immune activation. [ Time Frame: 7 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Cardiometabolic Effects of Eplerenone in HIV Infection
Official Title  ICMJE Cardiometabolic Effects of Eplerenone in HIV Infection
Brief 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.

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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Cardiac Steatosis
  • Hepatic Steatosis
Intervention  ICMJE 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.
Study Arms  ICMJE 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.
Intervention: Drug: Inspra /Eplerenone
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: June 21, 2018)
5
Original Estimated Enrollment  ICMJE
 (submitted: December 10, 2015)
50
Actual Study Completion Date  ICMJE September 11, 2017
Actual Primary Completion Date September 11, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02629094
Other Study ID Numbers  ICMJE 160030
16-I-0030
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )
Study Sponsor  ICMJE National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Colleen M Hadigan, M.D. National Institute of Allergy and Infectious Diseases (NIAID)
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date September 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP