Cardiometabolic Effects of Eplerenone in HIV Infection

Hepatic Steatosis Clinical Trial

Official title:

Cardiometabolic Effects of Eplerenone in HIV Infection

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02629094
• Other study ID #: 160030
• Secondary ID: 16-I-0030
• Status: Terminated
• Phase: Phase 2
• Start date: December 2, 2015
• Est. completion date: September 11, 2017

Study information

• Verified date: September 2017
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: September 11, 2017
• Est. primary completion date: September 11, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

• 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

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• Cardiac Steatosis
• Fatty Liver
• Hepatic Steatosis
• HIV Infections

Intervention

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.

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

References & Publications (4)

Chaudhury CS, Purdy JB, Liu CY, Morse CG, Stanley TL, Kleiner D, Hadigan C. Unanticipated increases in hepatic steatosis among human immunodeficiency virus patients receiving mineralocorticoid receptor antagonist eplerenone for non-alcoholic fatty liver d — View Citation

Hirata A, Maeda N, Hiuge A, Hibuse T, Fujita K, Okada T, Kihara S, Funahashi T, Shimomura I. Blockade of mineralocorticoid receptor reverses adipocyte dysfunction and insulin resistance in obese mice. Cardiovasc Res. 2009 Oct 1;84(1):164-72. doi: 10.1093/cvr/cvp191. Epub 2009 Jun 8. — View Citation

Suzuki J, Iwai M, Mogi M, Oshita A, Yoshii T, Higaki J, Horiuchi M. Eplerenone with valsartan effectively reduces atherosclerotic lesion by attenuation of oxidative stress and inflammation. Arterioscler Thromb Vasc Biol. 2006 Apr;26(4):917-21. Epub 2006 Jan 19. — View Citation

Triant VA, Lee H, Hadigan C, Grinspoon SK. Increased acute myocardial infarction rates and cardiovascular risk factors among patients with human immunodeficiency virus disease. J Clin Endocrinol Metab. 2007 Jul;92(7):2506-12. Epub 2007 Apr 24. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Improvement of Cardiac Steatosis: Mean Change in Intraventricular Septum Percentage of Lipid by MR Spectroscopy.	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
Primary	Improvement of Hepatic Steatosis: Mean Change in Hepatic Percentage of Lipid by MR Spectroscopy	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