Cardiometabolic Effects of Eplerenone in HIV Infection

NCT02629094 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 16003016-I-0030
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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.

Conditions

Cardiac Steatosis; Hepatic Steatosis

Keywords

Hepatic Steatosis; Cardiac Steatosis; Aldosterone; Eplerenone; Mineralcorticoid Receptor

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Study Arms (1)

Treatment

EXPERIMENTAL

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

Interventions

Inspra /Eplerenone DRUG

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.

Treatment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Increased waist circumference on the basis of National Cholesterol Education Program guidelines (\> 102 cm in men and \> 88 cm in women)
• Hepatic steatosis established by hepatic MRI greater than or equal to 5% and/or liver biopsy within the last 12 months
• HIV-infected, HIV viral load \< 50 copies/mL and no change in ART regimen for at least 3 months
• Age greater than or equal to 18 and less than or equal to 75 years
• Agree to have samples stored for future research

You may not qualify if:

• Estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73 m\^2, serum creatinine \> 1.5 mg/dL
• Serum potassium \> 5.5 mEq/L, alanine aminotransferase \> 2.5 times the upper limit of normal, hemoglobin (Hgb) \< 11 g/dL
• 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
• A blood pressure \< 90mmHg systolic or \< 50mm Hg diastolic
• Screening EKG with a significant heart block (e.g. PR \> 300 ms) or an EKG determined significant by Cardiology consult.
• Current hepatitis C infection, unless there has been a sustained virologic response for at least 12 months
• Type 2 diabetes with microalbuminuria
• 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.
• Use of angiotensin converting enzyme (ACE) inhibitors, angiotensin reporter blockers (ARBs), potassium-sparing diuretics, and other medications that may increase the risk of hyperkalemia
• Use of potassium supplementation or other medications known to increase potassium
• Concomitant use of strong inhibitors and/or inducers ofof cytochrome P450 isozyme (CYP)3A4
• If receiving testerone, estrogen or progesterone therapy, must be on a stable dose for at least 3 months.
• Current use of growth hormone or growth hormone-releasing hormone
• Current serious viral, bacterial, or other infection (excluding HIV)
• Current active substance abuse/dependence

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• 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. doi: 10.1210/jc.2006-2190. Epub 2007 Apr 24.

  PMID: 17456578 BACKGROUND

• 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.

  PMID: 19505930 BACKGROUND

• 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. doi: 10.1161/01.ATV.0000204635.75748.0f. Epub 2006 Jan 19.

  PMID: 16424347 BACKGROUND

• 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 disease. Liver Int. 2018 May;38(5):797-802. doi: 10.1111/liv.13734. Epub 2018 Mar 31.

  PMID: 29509992 RESULT

MeSH Terms

Conditions

Fatty Liver

Interventions

Eplerenone

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Hadigan, Colleen
• Organization: National Institute of Allergy and Infectious Diseases

hadiganc@mail.nih.gov

+1 301 594 5754

Study Officials

• Colleen M Hadigan, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2015
• First Posted: December 14, 2015
• Study Start: December 2, 2015
• Primary Completion: September 11, 2017
• Study Completion: September 11, 2017
• Last Updated: July 17, 2018
• Results First Posted: July 17, 2018

Record last verified: 2017-09

Locations

US (1)