Effect of Eplerenone on Endothelial Function in Metabolic Syndrome

NCT01319344 | Completed Phase 3 DMC

• 1 other identifier: MSyn-2010
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 2

Brief Summary

Patients with the metabolic syndrome (MetSyn) are at increased risk for cardiovascular mortality and morbidity.This increased cardiovascular risk is attributed to metabolic dysregulations like impaired glucose tolerance or diabetes mellitus and dyslipidemia, abdominal obesity and arterial hypertension, which promote oxidative stress and inflammation with consecutive endothelial dysfunction causing an atherogenic environment. Aldosterone promoted end organ damage is mainly found in the cardiovascular system and the kidney. Inflammation and activation of different factors promotes fibroblast growth and matrix production resulting in myocardial fibrosis, vascular remodelling and renal fibrosis. MetSyn and aldosterone are cardiovascular risk factors and it is of crucial importance to note that there is a connection between MetSyn and aldosterone. Other cross sectional studies show a direct correlation of aldosterone levels and impaired glucose metabolism in patients with and without the MetSyn. Taken together, aldosterone influences essential parameters of the MetSyn. Coincidentally parameters of the MetSyn are stimulus for an increased aldosterone synthesis, i.e. visceral adipocytes. In large scale clinical trials - RALES, EPHESUS, 4E - inhibition of MR has proven to be beneficial in patients with congestive heart failure and post myocardial infarction and this result has been confirmed for diabetic patients, who are known to have an increased cardiovascular risk. There is only very limited data on the impact of MR inhibition on metabolic, endocrine, and inflammatory parameters in patients with MetSyn, who have not yet suffered from cardiovascular events.

Conditions

Metabolic Syndrome; Endothelial Dysfunction

Outcome Measures

Primary Outcomes (1)

• Change of basal nitric oxide activity as assessed by change of retinal capillary flow (measured by Scanning Laser Doppler Flowmetry)

  Ten weeks

Secondary Outcomes (2)

• Changes of distensibility of the carotid artery.

  Ten weeks

• Change of flow mediated dilation of the brachial artery.

  Ten weeks

Study Arms (1)

Eplerenone

EXPERIMENTAL

Drug: Eplerenone

Interventions

Eplerenone DRUG

25 mg o.d. per os

Also known as: Inspra

Eplerenone

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Patients with or without antihypertensive therapy and mean blood pressure \> 160/100 mmHg
• Patients with secondary hypertension
• Patients with one antihypertensive agent maximally dosed or two (or less) agents with half (or less) of maximum approved dose
• Patients with diabetes mellitus type 1 or type 2
• Smokers and ex-smokers \< 1 year
• Female patients (to prevent effects of changes in endothelial function attributable to the menstrual cycle)
• Patients with sick sinus syndrome
• Patients with higher degree of sinoatrial or atrioventricular block (II-III)
• Patients with bradycardia (\< 50 beats/min)
• Patients with malignant arrhythmias
• Patients with known cardiovascular, disease
• Patients with known cerebrovacular disease
• Patients with peripheral occlusive artery disease
• Patients with history of epilepsy
• Patients with severe hepatic disease (serum GOT, GPT, gamma-GT, AP, bilirubin \> 300 of uppper normal range)

Sponsors & Collaborators

• University of Erlangen-Nürnberg Medical School: lead

Study Sites (2)

Clinical Research Unit, Department of Nephrology and Hypertension, University of Erlangen-Nurnberg

Erlangen, 91054, Germany

Location

Clinical Research Unit, Department of Nephrology and Hypertension, University of Erlangen-Nürnberg

Nuremberg, 90471, Germany

Location

Related Publications (2)

• Bosch AJ, Harazny JM, Kistner I, Friedrich S, Wojtkiewicz J, Schmieder RE. Retinal capillary rarefaction in patients with untreated mild-moderate hypertension. BMC Cardiovasc Disord. 2017 Dec 21;17(1):300. doi: 10.1186/s12872-017-0732-x.

  PMID: 29268712 DERIVED

• Jumar A, Harazny JM, Ott C, Kistner I, Friedrich S, Schmieder RE. Improvement in Retinal Capillary Rarefaction After Valsartan Treatment in Hypertensive Patients. J Clin Hypertens (Greenwich). 2016 Nov;18(11):1112-1118. doi: 10.1111/jch.12851. Epub 2016 Jun 16.

  PMID: 27306560 DERIVED

MeSH Terms

Conditions

Metabolic Syndrome

Interventions

Eplerenone

Condition Hierarchy (Ancestors)

Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Roland E Schmieder, Prof

  University of Erlangen-Nurnberg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. med.

Study Record Dates

• First Submitted: March 17, 2011
• First Posted: March 21, 2011
• Study Start: September 1, 2010
• Primary Completion: December 1, 2012
• Study Completion: April 1, 2013
• Last Updated: April 17, 2013

Record last verified: 2013-04

Locations

DE (2)