NCT02809963

Mineralocorticoid Receptor Antagonists in Type 2 Diabetes

A Randomized, Double-blind, Placebo-controlled Study of the Effect of Mineralocorticoid Receptor Antagonists in Type 2 Diabetes Patients on Myocardial Function, Glucose and Fat Metabolism (The MIRAD-study)

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 140 (actual)
• Sponsor: Herlev Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 85 Years
• Healthy volunteers: Not accepted

Summary

The aim of this study is to investigate the effect of selective blocking of the mineralocorticoid receptor in patients with type 2 diabetes on insulin resistance, lipid metabolism and myocardial function.

Detailed description

In this randomized, double-blind, placebo-controlled study we want to investigate the effect of mineralocorticoid receptor antagonists in type 2 diabetes patients on myocardial function, glucose and fat metabolism. Background The mortality rate in T2 DM is still increased by almost a factor 2 although poly pharmacological therapy of risk factors has been recommended for years. Treatment with MR antagonists in patients with primary hyperaldosteronism and systolic heart failure improves insulin resistance, myocardial function and prognosis. Further, recent evidence has suggested that aldosterone participates in the regulation of glucose and lipid metabolism, as MR expression has been identified in adipocytes and beneficial metabolic effects of selective MR blockade has been demonstrated in several animal models. Notably, there is no available data in humans with T2DM. A key feature of T2 DM is altered body composition characterized by increased metabolic active visceral adipose tissue (VAT) and increased fat content of the liver, which has been associated with cardiac dysfunction and outcome. Gold standard for measurement of VAT is magnetic resonance imaging (MRI), and proton MRI spectroscopy can quantitatively measure fat content in the liver with high precision. The pathogenesis of myocardial dysfunction in T2DM is linked with insulin resistance (IR) of adipose tissue mediating increased supply of free fatty acids and intra myocardial lipid accumulation. Thus, beneficial effects of lipid metabolism could in theory indirectly improve myocardial function in type 2 diabetics. Global longitudinal strain (GLS) is a validated method for evaluating regional and global function of the left ventricle, which is a strong predictor of incident HF in patients with myocardial infarction and closely related with plasma NT-proBNP concentrations. Hypothesis Selective blocking of the MR receptor in patients with T2 DM improves insulin resistance, lipid metabolism and myocardial function. Objectives To investigate the effect of Eplerenone 100-200 mg once daily compared to placebo in patients with type 2 diabetes with regard to glucose and lipid metabolism, myocardial function and structure, and vascular function. The primary objective is to investigate the effect of Eplerenone 100-200 mg once daily compared to placebo on changes in liver fat content. Design A single center, randomized, double blinded placebo controlled trial. Patients with T2 DM and high risk of cardiovascular disease will be randomized to either Eplerenone 100-200 mg or placebo daily for 26 weeks. Patients will be investigated at baseline and after 26 weeks. A total of 130 patients with type 2 diabetes will be included.

Conditions

• Diabetes Type 2

Interventions

Type	Name	Description
DRUG	Eplerenone	50 mg tablets, oral use.
DRUG	Placebo	50 mg tablets, oral use

Timeline

• Start date: 2015-11-01
• Primary completion: 2017-11-01
• Completion: 2017-11-01
• First posted: 2016-06-22
• Last updated: 2018-06-01

Locations

1 site across 1 country: Denmark