Eplerenone in HIV Associated Abdominal Fat Accumulation

Not Applicable

Completed

• Conditions: HIV
• Interventions: Drug: Eplerenone and lifestyle; Other: placebo and lifestyle

• Registration Number: NCT01405456
• Lead Sponsor: Massachusetts General Hospital

Brief Summary

The purpose of this study is to test the effects of a drug, eplerenone, along with lifestyle modification to affect sugar metabolism, body fat distribution, and cardiovascular health in HIV-infected individuals. In non-HIV-infected individuals, recent data has shown that aldosterone, a hormone that regulates salt and water balance, is increased in association with increased belly fat and decreased insulin sensitivity. In HIV-infected individuals, aldosterone appears to be higher in individuals with increased belly fat, and increased aldosterone appears to be strongly associated with impaired sugar metabolism. In this study, the investigators will test the effects of eplerenone, which is a medication that blocks the actions of aldosterone, along with lifestyle modification. The investigators hypothesize that eplerenone may improve sugar metabolism, improve markers of cardiovascular health, and reduce fat accumulation in liver and muscle.

Detailed Description

The study is 12 months long, with two phases. In the initial, 6-month phase, volunteers are randomly assigned to receive either eplerenone or placebo (an inactive pill). In addition, all volunteers will receive counseling about healthy diet and lifestyle, and will be asked to follow guidelines for a healthy level of physical activity. In the second 6-months of the study, all volunteers will continue to receive lifestyle modification and all will receive eplerenone.

Study Timeline

• Study First Submitted: 2011-07-27
• Study First Submitted QC: 2011-07-28
• Study First Posted: 2011-07-29
• Study Start: 2012-01
• Primary Completion: 2017-05-03
• Study Completion: 2017-11-01
• Results First Submitted: 2018-04-16
• Results First Submitted QC: 2018-04-16
• Status Verified: 2018-05
• Results First Posted: 2018-05-16
• Last Update Submitted: 2018-05-16
• Last Update Posted: 2018-06-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 46

Inclusion Criteria

1. Increased waist circumference based on NCEP guidelines (>102cm in men and >88cm in women) and impaired glucose tolerance (either IFG > 100 mg/dL but < 126 mg/dL or 2hr glucose > 140 mg/dl but < 200 mg/dL, or fasting insulin >12 uIU/mL)
2. HIV positive for 5y and on a stable ART regimen for at least 12 months
3. Age ≥ 30 and ≤ 65 years of age

Exclusion Criteria

1. ACE Inhibitor, ARB, verapamil, or spironolactone
2. Potassium supplementation
3. Estimated GFR<60, creatinine > 1.5 mg/dL
4. Serum K > 5.5 mEq/L, ALT > 2.5 times the upper limit of normal, Hgb < 11g/dL
5. Uncontrolled hypertension (SBP ≥ 160 or DBP ≥ 100)
6. Current or prior steroid use within past 6 months
7. Known history of diabetes mellitus or current use of anti-diabetic medications
8. Concomitant use of full dose ritonavir, nelfinavir, clarithromycin and other strong inhibitors of CYP34A
9. Use of St. John's Wart (CYP3A4 inducer)
10. Pregnant or actively seeking pregnancy, breastfeeding
11. For women: Pregnant or actively seeking pregnancy, breastfeeding, failure to use an acceptable non-hormonal form of birth control, including abstinence, barrier contraceptives, or non-hormonal IUD.
12. Estrogen or progestational derivative use within 3 months
13. Testosterone use for non-physiologic purposes, or physiologic testosterone replacement for < 3 months.
14. Current growth hormone or growth hormone releasing hormone use
15. Current viral, bacterial or other infections (excluding HIV)
16. Current active substance abuse
17. Patients with a significant history of cardiovascular disease, including prior MI or stroke

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Eplerenone and Lifestyle	Eplerenone and lifestyle	First 6 months: eplerenone 50mg daily along with lifestyle modification (counseling regarding lifestyle and diet, as well as following healthy activity guidelines) Second 6 months: same (eplerenone open label during second 6 months)
Placebo and Lifestyle	placebo and lifestyle	First 6 months: placebo pill daily along with lifestyle modification (counseling regarding lifestyle and diet, as well as following healthy activity guidelines) Second 6 months: eplerenone (open label) 50mg daily along with continued lifestyle modification

Primary Outcome Measures

Name	Time	Method
Insulin Stimulated Glucose Uptake	6 months

Secondary Outcome Measures

Name	Time	Method
Markers of Immune Activation	6 months	MCP-1
Liver Fat	6 months
C-Reactive Protein	6 months
Plasminogen Activator Inhibitor 1	6 months
Intramyocellular Lipid	6 months
Flow Mediated Vasodilation	6 months
Hemoglobin A1c	6 months
Adiponectin	6 months
Markers of Systemic Inflammation	6 months	IL-6
Visceral Adipose Tissue	6 months
Potassium	6 months

Trial Locations

Locations (1)

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States