Clinical trial NCT01405456: Eplerenone in HIV Associated Abdominal Fat Accumulation
Official title: Randomized Placebo-controlled Trial to Investigate the Effects of Eplerenone in Patients With HIV-associated Abdominal Fat Accumulation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV
Keywords: HIV-infection
eplerenone
aldosterone
visceral fat
lipodystrophy
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2011-07-29
Enrollment: 46
Sex: ALL
Minimum age (years): 30
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Insulin Stimulated Glucose Uptake
timeFrame: 6 months
Secondary outcomes:
measure: Visceral Adipose Tissue
timeFrame: 6 months
measure: Liver Fat
timeFrame: 6 months
measure: Intramyocellular Lipid
timeFrame: 6 months
measure: Flow Mediated Vasodilation
timeFrame: 6 months
measure: Potassium
timeFrame: 6 months
measure: Hemoglobin A1c
timeFrame: 6 months
measure: C-Reactive Protein
timeFrame: 6 months
measure: Plasminogen Activator Inhibitor 1
timeFrame: 6 months
measure: Adiponectin
timeFrame: 6 months
measure: Markers of Systemic Inflammation
timeFrame: 6 months
measure: Markers of Immune Activation
timeFrame: 6 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Steven Grinspoon, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.