Mineralocorticoid Receptor Antagonists in Type 2 Diabetes
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02809963|
Recruitment Status : Completed
First Posted : June 22, 2016
Last Update Posted : June 1, 2018
|Condition or disease||Intervention/treatment||Phase|
|Diabetes Type 2||Drug: Eplerenone Drug: Placebo||Phase 4|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||140 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||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)|
|Study Start Date :||November 2015|
|Actual Primary Completion Date :||November 2017|
|Actual Study Completion Date :||November 2017|
Active Comparator: Eplerenone
Eplerenone 50 mg tablets. 2-4 tablets once daily for 26 weeks
50 mg tablets, oral use.
Placebo Comparator: placebo
sugar pill manufactured to mimic Eplerenone 50 mg tablet. 2-4 tablets once daily for 26 weeks.
50 mg tablets, oral use
- Liver fat content [ Time Frame: 26 weeks ]changes in liver fat content by proton MR spectroscopy
- Fat mass distribution [ Time Frame: 26 weeks ]Changes in body fat distribution (total body fat, visceral fat, subcutaneous fat)
- insulin resistance [ Time Frame: 26 weeks ]Changes in insulin resistance by HOMA and Matsuda index
- Urinary albumin/creatinine ratio [ Time Frame: 26 weeks ]changes in Urinary albumin/creatinine ratio
- Biomarkers of adipocyte function [ Time Frame: 26 weeks ]Changes in biomarkers of adipocyte function (adiponectin, leptin, FGF-21, TNF-alfa, FFA, IL-6, MCP-1, MAC-1)
- 24 Hour blood pressure [ Time Frame: 26 weeks ]changes in 24 Hour blood pressure
- Global longitudinal strain (GLS) [ Time Frame: 26 weeks ]changes in global longitudinal strain by echocardiography
- systolic and diastolic function og left ventricule [ Time Frame: 26 weeks ]changes in systolic and diastolic function of left ventricule by echocardiography
- Regional and global fibrosis by cardiac magnetic resonance [ Time Frame: 26 weeks ]changes in regional and global fibrosis using Late gadolineum enhancement cardiac magnetic resonance
- biomarkers of myocardial stress and fibrosis [ Time Frame: 26 weeks ]changes in biomarkers of myocardial stress and fibrosis (NT-proBNP, MR-proANP, galectin-3, GDF-15, MR-proADM)
- pulse wave analysis [ Time Frame: 26 weeks ]changes in pulse wave analysis
- Quality of life [ Time Frame: 26 weeks ]changes in quality of life using WHO-5
- Diabetes related changes in quality of life [ Time Frame: 26 weeks ]changes in quality of life using W-BQ12
- kidney function [ Time Frame: 26 weeks ]changes in creatinine and eGFR
- potassium [ Time Frame: 26 weeks ]changes in potassium
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02809963
|Herlev and Gentofte Hospital, Department of Endocrinology and Metabolism, Department of internal medicine,|
|Herlev, Denmark, 2730|