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Role of Mineralocorticoid Receptor in Diabetic Cardiovascular Disease

This study has been completed.
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Gail Kurr Adler, Brigham and Women's Hospital
ClinicalTrials.gov Identifier:
NCT00865124
First received: March 17, 2009
Last updated: May 19, 2017
Last verified: May 2017
March 17, 2009
May 19, 2017
September 2008
August 2013   (Final data collection date for primary outcome measure)
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.
MR blockade improves coronary circulatory and cardiac diastolic function in individuals with T2DM [ Time Frame: two and six months ]
Complete list of historical versions of study NCT00865124 on ClinicalTrials.gov Archive Site
  • 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.
MR blockade improves renovascular function in subjects with T2DM [ Time Frame: two and six months ]
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Role of Mineralocorticoid Receptor in Diabetic Cardiovascular Disease
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:

  1. spironolactone
  2. hydrochlorothiazide (HCTZ) plus potassium
  3. placebo

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.

Not Provided
Interventional
Not Provided
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Investigator
Primary Purpose: Treatment
  • Type 2 Diabetes Mellitus
  • Vascular Disease
  • Drug: Spironolactone
    25 mg capsule daily for 6 months
  • Drug: Hydrochlorothiazide + potassium
    hydrochlorothiazide (HCTZ) + potassium, 12.5 mg/10 milliequivalents (mEq) capsule daily
  • Other: Placebo
    Placebo capsule daily
  • Experimental: Spironolactone (mineralocorticoid receptor [MR] blockade)
    Intervention: Drug: Spironolactone
  • Active Comparator: Hydrochlorothiazide + potassium
    Intervention: Drug: Hydrochlorothiazide + potassium
  • Placebo Comparator: Placebo capsule
    Intervention: Other: Placebo
Garg R, Rao AD, Baimas-George M, Hurwitz S, Foster C, Shah RV, Jerosch-Herold M, Kwong RY, Di Carli MF, Adler GK. Mineralocorticoid receptor blockade improves coronary microvascular function in individuals with type 2 diabetes. Diabetes. 2015 Jan;64(1):236-42. doi: 10.2337/db14-0670. Epub 2014 Aug 14.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
69
May 2014
August 2013   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • age 18-70 years
  • type 2 diabetes mellitus
  • with or without hypertension

Exclusion Criteria:

  • ischemic changes on resting electrocardiogram,
  • clinical evidence of heart disease (angina, heart failure, unstable angina),cerebrovascular or peripheral vascular disease,
  • significant cardiac arrhythmias,
  • aortic stenosis,
  • 2nd or 3rd degree atrio-ventricular block, sinus node disease, or symptomatic bradycardia,
  • bronchospastic lung disease with active wheezing,
  • known hypersensitivity to adenosine,
  • hemoglobin A1C (HbA1c) > 8.5%, *
  • gout (If not already taking HCTZ),
  • the use of Rosiglitazone,**
  • estimated glomerular filtration rate (eGFR) < 60 ml/min,
  • serum potassium > 5.0 mmol/L,
  • use of potassium-sparing diuretics,**
  • current smoker,*
  • pregnancy,
  • renal disease not related to diabetes mellitus,
  • uncontrolled hypertension, systolic blood pressure (BP) >160 mm Hg and diastolic BP >100 mm Hg,*
  • use of cyclic hormone replacement therapy
  • past intolerance of angiotensin-converting enzyme (ACE) inhibitor therapy
  • other major medical illnesses. Participants with evidence of a previous myocardial infarction on the first adenosine-stimulated positron emission tomography (PET) study will be withdrawn from the study.
  • Screening systolic blood pressure < 105 mm Hg off of anti-hypertensive medications

    • Participants can enroll in study and proceed with in-patient evaluations if during the run-in period adjustments of medications, diet and habits lead to improved glucose control [equivalent to HbA1c <8.5%, controlled hypertension and cessation of smoking.

      • Participants who are currently taking these medications will not qualify for a screening visit. If medications were recently stopped by the participant's physician, he or she may be screened but the baseline assessment protocol must occur 3 months after stopping.
Sexes Eligible for Study: All
18 Years to 70 Years   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00865124
2007-P-000564
1R01HL087060-01A2 ( US NIH Grant/Contract Award Number )
Yes
Not Provided
Not Provided
Not Provided
Gail Kurr Adler, Brigham and Women's Hospital
Brigham and Women's Hospital
  • National Institutes of Health (NIH)
  • National Heart, Lung, and Blood Institute (NHLBI)
Principal Investigator: Gail K Adler, MD, PhD Brigham and Women's Hospital
Brigham and Women's Hospital
May 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP