Role of Mineralocorticoid Receptor in Diabetic Cardiovascular Disease
Aldosterone is a significant mediator of cardiovascular injury associated with heart failure and the cardiovascular benefits of mineralocorticoid receptor blockade are additive to those of angiotensin converting enzyme inhibitors or angiotensin II (ANGII) receptor blockers. This study will test the hypothesis that mineralocorticoid receptor (MR) antagonists exert beneficial cardiovascular effects, specifically by decreasing vascular injury and improving vascular function. A randomized, double-blind study will be conducted, in which participants with Type 2 Diabetes Mellitus will undergo a series of assessments to test heart, blood vessel, and kidney function at baseline, and after 2 and 6 months of treatment with one of the following drugs:
- hydrochlorothiazide (HCTZ) plus potassium
In the event of insufficient funds, randomization to the placebo arm will be stopped and primary assessment of outcomes will occur at baseline and after 6 months of treatment.
|Type 2 Diabetes Mellitus Vascular Disease||Drug: Spironolactone Drug: Hydrochlorothiazide + potassium Other: Placebo|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Investigator
Primary Purpose: Treatment
|Official Title:||Role of Mineralocorticoid Receptor in Diabetic Cardiovascular Disease|
- Change in Coronary Flow Reserve From Baseline to 6 Months [ Time Frame: Baseline and six months ]Coronary flow reserve (CFR), or myocardial perfusion reserve, was assessed via cardiac positron emission tomography (PET). CFR is the ratio of adenosine-stimulated blood flow through myocardium to resting blood flow through myocardium. An improvement in coronary flow reserve is beneficial.
- Change in Mitral Annulus Velocities on Tissue Doppler (Delta E/e' Ratio), a Measure of Diastolic Function [ Time Frame: Baseline and six months ]Diastolic function was assessed via tissue doppler imaging (TDI) by echocardiography to determine left ventricular diastolic function before and after 6 months of treatment.
- Mitral Annulus Velocities on Tissue Doppler (Delta E/e' Ratio), a Measure of Diastolic Function (With Angiotensin II) [ Time Frame: Baseline and six months ]Diastolic function was assessed via tissue doppler imaging (TDI) by echocardiography to determine left ventricular diastolic function before and after 6 months of treatment; and in response to acute administration (3 nanograms/kg/min for 60 min) of the vasoactive agent, Angiotensin II.
- Change in Renal Plasma Flow [ Time Frame: Baseline and six months ]Renal vasculature was assessed by examining renal plasma flow, or para-aminohippurate (PAH) clearance, basally and in response to acute administration (3 nanograms/kg/min for 60 min) of the vasoactive agent, Angiotensin II.
|Study Start Date:||September 2008|
|Study Completion Date:||May 2014|
|Primary Completion Date:||August 2013 (Final data collection date for primary outcome measure)|
|Experimental: Spironolactone (mineralocorticoid receptor [MR] blockade)||
25 mg capsule daily for 6 months
|Active Comparator: Hydrochlorothiazide + potassium||
Drug: Hydrochlorothiazide + potassium
hydrochlorothiazide (HCTZ) + potassium, 12.5 mg/10 milliequivalents (mEq) capsule daily
|Placebo Comparator: Placebo capsule||
Placebo capsule daily
Please refer to this study by its ClinicalTrials.gov identifier: NCT00865124
|United States, Massachusetts|
|Brigham and Women's Hospital|
|Boston, Massachusetts, United States, 02115|
|Principal Investigator:||Gail K Adler, MD, PhD||Brigham and Women's Hospital|