Eplerenone in HIV Associated Abdominal Fat Accumulation

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Massachusetts General Hospital
Sponsor:
Information provided by (Responsible Party):
Steven K. Grinspoon, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01405456
First received: July 27, 2011
Last updated: May 2, 2014
Last verified: May 2014
  Purpose

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 Intervention
HIV
Drug: Eplerenone and lifestyle
Other: placebo and lifestyle

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Insulin stimulated glucose uptake [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Insulin stimulated glucose uptake measured during euglycemic hyperinsulinemic clamp procedure


Secondary Outcome Measures:
  • visceral adipose tissue [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    visceral adipose tissue area as measured by single-slice computed tomography scan of the abdomen

  • liver fat [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    hepatic (liver) fat as measured by magnetic resonance spectroscopy

  • intramyocellular lipid [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    intramyocellular lipid of calf muscles as measured by magnetic resonance spectroscopy

  • flow mediated vasodilation [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • potassium [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    serum measurements of potassium

  • hemoglobin A1c [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • c-reactive protein [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • plasminogen activator inhibitor 1 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • adiponectin [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 66
Study Start Date: January 2012
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   30 Years to 65 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01405456

Contacts
Contact: Katie Fitch, NP 617-724-8015 kfitch@partners.org

Locations
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Principal Investigator: Steven Grinspoon, MD Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: Steven K. Grinspoon, MD, Principal Investigator, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01405456     History of Changes
Other Study ID Numbers: 2010P002095
Study First Received: July 27, 2011
Last Updated: May 2, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
HIV-infection
eplerenone
aldosterone
visceral fat
lipodystrophy

Additional relevant MeSH terms:
Eplerenone
Spironolactone
Mineralocorticoid Receptor Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Diuretics, Potassium Sparing
Diuretics
Natriuretic Agents
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 20, 2014