Eplerenone in HIV Associated Abdominal Fat Accumulation

• ClinicalTrials.gov Identifier: NCT01405456
• Recruitment Status: Completed
• First Posted: July 29, 2011
• Results First Posted: May 16, 2018
• Last Update Posted: June 15, 2018
• Sponsor: Massachusetts General Hospital
• Information provided by (Responsible Party): Steven K. Grinspoon, MD, Massachusetts General Hospital

Study Description

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.

Condition or disease	Intervention/treatment	Phase
HIV	Drug: Eplerenone and lifestyle; Other: placebo and lifestyle	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 46 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Randomized Placebo-controlled Trial to Investigate the Effects of Eplerenone in Patients With HIV-associated Abdominal Fat Accumulation
• Study Start Date: January 2012
• Actual Primary Completion Date: May 3, 2017
• Actual Study Completion Date: November 1, 2017

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Insulin Stimulated Glucose Uptake [ Time Frame: 6 months ]

Secondary Outcome Measures :

1. Visceral Adipose Tissue [ Time Frame: 6 months ]
2. Liver Fat [ Time Frame: 6 months ]
3. Intramyocellular Lipid [ Time Frame: 6 months ]
4. Flow Mediated Vasodilation [ Time Frame: 6 months ]
5. Potassium [ Time Frame: 6 months ]
6. Hemoglobin A1c [ Time Frame: 6 months ]
7. C-Reactive Protein [ Time Frame: 6 months ]
8. Plasminogen Activator Inhibitor 1 [ Time Frame: 6 months ]
9. Adiponectin [ Time Frame: 6 months ]
10. Markers of Systemic Inflammation [ Time Frame: 6 months ]
    IL-6
11. Markers of Immune Activation [ Time Frame: 6 months ]
    MCP-1

Eligibility Criteria

• Ages Eligible for Study: 30 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

Sponsors and Collaborators

Massachusetts General Hospital

Investigators

• Principal Investigator: Steven Grinspoon, MD; Massachusetts General Hospital

  Study Documents (Full-Text)

Documents provided by Steven K. Grinspoon, MD, Massachusetts General Hospital:

Study Protocol and Statistical Analysis Plan  [PDF] December 1, 2016

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Steven K. Grinspoon, MD, Principal Investigator, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT01405456
• Other Study ID Numbers: 2010P002095
• First Posted: July 29, 2011
• Results First Posted: May 16, 2018
• Last Update Posted: June 15, 2018
• Last Verified: May 2018

Keywords provided by Steven K. Grinspoon, MD, Massachusetts General Hospital:

HIV-infection; eplerenone; aldosterone; visceral fat; lipodystrophy

Additional relevant MeSH terms:

Eplerenone; Mineralocorticoid Receptor Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Diuretics, Potassium Sparing; Diuretics; Natriuretic Agents; Antihypertensive Agents