Randomized, Placebo-Controlled Trial to Evaluate Effects of Eplerenone on Metabolic and Inflammatory Indices in HIV.

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Randomized, Placebo-Controlled Trial to Evaluate Effects of Eplerenone on Metabolic and Inflammatory Indices in HIV.

J Clin Endocrinol Metab. 2018 Apr 05;:

Authors: 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

Abstract
Context: HIV-infected individuals demonstrate unique RAAS physiology, with increased RAAS activation in association with visceral adiposity, insulin resistance, and inflammation. A physiologically-based treatment approach targeting mineralocorticoid receptor (MR) blockade may improve metabolic and inflammatory indices in HIV.
Objective: To investigate effects of eplerenone on insulin sensitivity, inflammatory indices and other metabolic parameters in HIV.
Design: Six month, double-blind, randomized, placebo-controlled trial.
Setting: Academic clinical research center.
Participants: HIV-infected individuals with increased waist circumference and abnormal glucose homeostasis.
Intervention: Eplerenone 50mg or placebo daily.
Outcome: The primary endpoint was change in insulin stimulated glucose uptake normalized to insulin and lean body mass (M/I/LBM) measured by the euglycemic hyperinsulinemic clamp technique. Secondary endpoints included change in body composition and markers of inflammation.
Results: Forty-six individuals were randomized to eplerenone (n=25) vs. placebo (n=21). Eplerenone did not improve insulin sensitivity [M/I/LBM (0.48 [-1.28,1.48] vs. 0.43 [-1.95,2.55] mg/min per μIU/mL, P=0.71, eplerenone vs. placebo) when measured by the gold standard euglycemic hyperinsulinemic clamp technique. IMCL (P=0.04), MCP-1(P=0.04), and HDL (P=0.04) improved among those randomized to eplerenone vs. placebo. Trends toward decreases in IL-6 (P=0.10) and hsCRP (P=0.10) were also seen with eplerenone vs. placebo. Plasma renin activity and aldosterone levels increased in the eplerenone vs. placebo-treated group demonstrating expected physiology. MR antagonism with eplerenone was well-tolerated among the HIV population with no significant changes in blood pressure or potassium.
Conclusion: MR blockade may improve selected metabolic and inflammatory indices in HIV-infected individuals. Further studies are necessary to understand the clinical potential of MR antagonism in HIV.

PMID: 29659888 [PubMed - as supplied by publisher]

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