Mineralocorticoid Receptor Antagonists in Type 2 Diabetes

NCT02809963 | Completed Phase 4 DMC

• 1 other identifier: 2015-002519-14
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Diabetes Type 2

Outcome Measures

Primary Outcomes (1)

• Liver fat content

  changes in liver fat content by proton MR spectroscopy

  26 weeks

Secondary Outcomes (14)

• Fat mass distribution

  26 weeks

• insulin resistance

  26 weeks

• Urinary albumin/creatinine ratio

  26 weeks

• Biomarkers of adipocyte function

  26 weeks

• 24 Hour blood pressure

  26 weeks

Study Arms (2)

Eplerenone

ACTIVE COMPARATOR

Eplerenone 50 mg tablets. 2-4 tablets once daily for 26 weeks

Drug: Eplerenone

placebo

PLACEBO COMPARATOR

sugar pill manufactured to mimic Eplerenone 50 mg tablet. 2-4 tablets once daily for 26 weeks.

Drug: Placebo

Interventions

Eplerenone DRUG

50 mg tablets, oral use.

Eplerenone

Placebo DRUG

50 mg tablets, oral use

placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to understand the written patient information and to give informed consent
• Type 2 diabetes mellitus (WHO criteria), diagnosed at least 3 months prior to baseline
• Blood pressure treatment according to standard guidelines
• Negative pregnancy test (fertile women)
• Be willing to change/pause potassium sparing medication
• Age 18-85 years
• Patients must have high cardiovascular risk factors, defined as one of the following:
• NT-proBNP ≥ 70 pg/ml (taken within the last 6 months prior to baseline) Albuminuria ( albumin/creatinine ratio ≥ 30 mg/g Confirmed history of myocardial infarction (≥ 3 months prior to baseline) Or patient discharged from hospital with a documented diagnosis of unstable angina within 24 months prior to baseline Evidence of coronary artery disease by CAG in 1 or more major coronary arteries OR at least one of the following: a positive noninvasive stress test, OR a positive stress echocardiography showing regional systolic wall motion abnormalities, OR a positive scintigraphy test showing stress-induced ischemia History of ischemic or hemorrhagic stroke (≥ 3 months prior to informed consent) Presence of peripheral artery disease (symptomatic or not ) documented by either: previous limb angioplasty, stenting or bypass surgery; or previous limb or foot amputation due to circulatory insufficiency; or angiographic evidence of significant (≥ 50%) peripheral artery stenosis in at least one limb; or evidence from a non-invasive measurement of significant (≥50% or as reported as hemodynamically significant) peripheral artery stenosis in at least one limb; or ankle brachial index of ≤ 0.9
• Left ventricle hypertrophy:
• Documented at echocardiography ECG: R-spike in V5/V6 ≥ 25 mm or S-spike in V1 + R-spike in V5/V6 ≥ 35 mm Patients both with and without a cardiovascular risk factor can be randomized to the fat biopsy sub study.

You may not qualify if:

• Allergic to the study medication
• Systolic HF (LVEF ≤ 40%)
• Impaired kidney function, eGFR ≤ 40 ml/min
• Severe liver insufficiency (Child-Pugh class C)
• Treatment with MR antagonist within 3 months prior to baseline
• Treatment with both ACE inhibitors and Angiotensin II Receptor blockers.
• Serum-potassium ≥ 5.0 mmol/l
• Serum-sodium ≤ 135 mmol/l
• Myocardial infarction, unstable angina pectoris or bypass graft surgery within 3 months prior to baseline
• Persistant atrial fibrillation (except for the fat biopsy sub population)
• ECG showing malign ventricular arrhythmia or prolonged QT-interval (\> 500ms)
• Untreated heart valve disease
• ICD-unit/pacemaker
• Pregnancy or desire hereof or breastfeeding
• Women in the fertile age not using safe contraceptives (spiral, hormonal contraceptives)

Sponsors & Collaborators

• Herlev Hospital: lead

Study Sites (1)

Herlev and Gentofte Hospital, Department of Endocrinology and Metabolism, Department of internal medicine,

Herlev, 2730, Denmark

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Eplerenone

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD student

Study Record Dates

• First Submitted: June 16, 2016
• First Posted: June 22, 2016
• Study Start: November 1, 2015
• Primary Completion: November 1, 2017
• Study Completion: November 1, 2017
• Last Updated: June 1, 2018

Record last verified: 2018-05

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)