Eplerenone in HIV Associated Abdominal Fat Accumulation

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

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.

Study Overview

• Status: Completed
• Conditions: HIV
• Intervention / Treatment: Drug: Eplerenone and lifestyle; Other: placebo and lifestyle

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 Type: Interventional
• Enrollment (Actual): 46
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 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)	Drug: Eplerenone and lifestyle; eplerenone 50mg by mouth daily as well as lifestyle counseling
PLACEBO_COMPARATOR: 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	Other: placebo and lifestyle; placebo pill daily and lifestyle counseling

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Insulin Stimulated Glucose Uptake	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemoglobin A1c		6 months
Visceral Adipose Tissue		6 months
Liver Fat		6 months
Intramyocellular Lipid		6 months
Flow Mediated Vasodilation		6 months
Potassium		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

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital

Publications and helpful links

General Publications

• Srinivasa S, deFilippi C, Fitch KV, Iyengar S, Shen G, Burdo TH, Walpert AR, Thomas TS, Adler GK, Grinspoon SK. Evaluation of Mineralocorticoid Receptor Antagonism on Changes in NT-proBNP Among Persons With HIV. J Endocr Soc. 2021 Nov 19;6(1):bvab175. doi: 10.1210/jendso/bvab175. eCollection 2022 Jan 1.
• Srinivasa S, Fitch KV, Wong K, O'Malley TK, Maehler P, Branch KL, Looby SE, Burdo TH, Martinez-Salazar EL, Torriani M, Lyons SH, Weiss J, Feldpausch M, Stanley TL, Adler GK, Grinspoon SK. Randomized, Placebo-Controlled Trial to Evaluate Effects of Eplerenone on Metabolic and Inflammatory Indices in HIV. J Clin Endocrinol Metab. 2018 Jun 1;103(6):2376-2384. doi: 10.1210/jc.2018-00330.

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (ACTUAL): May 3, 2017
• Study Completion (ACTUAL): November 1, 2017

Study Registration Dates

• First Submitted: July 27, 2011
• First Submitted That Met QC Criteria: July 28, 2011
• First Posted (ESTIMATE): July 29, 2011

Study Record Updates

• Last Update Posted (ACTUAL): June 15, 2018
• Last Update Submitted That Met QC Criteria: May 16, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: aldosterone; visceral fat; lipodystrophy; eplerenone; HIV-infection
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Antihypertensive Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Natriuretic Agents; Diuretics; Hormone Antagonists; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Eplerenone
• Other Study ID Numbers: 2010P002095