Eplerenone in HIV Associated Abdominal Fat Accumulation

Study Overview
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Brief Summary
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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
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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.

Official Title
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Randomized Placebo-controlled Trial to Investigate the Effects of Eplerenone in Patients With HIV-associated Abdominal Fat Accumulation

Conditions
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HIV

Intervention / Treatment
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* Drug: Eplerenone and lifestyle
* Other: placebo and lifestyle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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) HIV positive for 5y and on a stable ART regimen for at least 12 months Age ≥ 30 and ≤ 65 years of age Exclusion Criteria: ACE Inhibitor, ARB, verapamil, or spironolactone Potassium supplementation Estimated GFR<60, creatinine > 1.5 mg/dL Serum K > 5.5 mEq/L, ALT > 2.5 times the upper limit of normal, Hgb < 11g/dL Uncontrolled hypertension (SBP ≥ 160 or DBP ≥ 100) Current or prior steroid use within past 6 months Known history of diabetes mellitus or current use of anti-diabetic medications Concomitant use of full dose ritonavir, nelfinavir, clarithromycin and other strong inhibitors of CYP34A Use of St. John's Wart (CYP3A4 inducer) Pregnant or actively seeking pregnancy, breastfeeding 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. Estrogen or progestational derivative use within 3 months Testosterone use for non-physiologic purposes, or physiologic testosterone replacement for < 3 months. Current growth hormone or growth hormone releasing hormone use Current viral, bacterial or other infections (excluding HIV) Current active substance abuse Patients with a significant history of cardiovascular disease, including prior MI or stroke

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Eplerenone and Lifestyle<br>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) | Drug: Eplerenone and lifestyle<br>* eplerenone 50mg by mouth daily as well as lifestyle counseling<br>|
| Placebo Comparator: Placebo and Lifestyle<br>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 | Other: placebo and lifestyle<br>* placebo pill daily and lifestyle counseling<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin Stimulated Glucose Uptake |  | 6 months | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV-infection, eplerenone, aldosterone, visceral fat, lipodystrophy