Mineralocorticoid Receptor Antagonists in Type 2 Diabetes

• Status: Completed
• Trial end date: 2017-11-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Herlev Hospital
• Treatments: Eplerenone; Mineralocorticoid Receptor Antagonists; Mineralocorticoids; Spironolactone

Criteria

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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)

• Cancer unless complete remission ≥ 5 year

• Alcohol-/drug-abuse

• Inflammatory bowel disease

• Other concomitant disease or treatment that according to the investigator's assessment makes the patient unsuitable to participate in the study

• Simultaneous participation in another clinical study

• Treatment with CYP3A4-inhibitors (e.g. itraconazol, etoconazol, ritonavir, nelfinavir, clarithromycin, telithromycin and nefazodon)