Role of Mineralocorticoid Receptor in Diabetic Cardiovascular Disease

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Gail Kurr Adler, Brigham and Women's Hospital
ClinicalTrials.gov Identifier:
NCT00865124
First received: March 17, 2009
Last updated: July 31, 2013
Last verified: July 2013

March 17, 2009
July 31, 2013
September 2008
January 2013   (final data collection date for primary outcome measure)
MR blockade improves coronary circulatory and cardiac diastolic function in individuals with T2DM [ Time Frame: two and six months ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00865124 on ClinicalTrials.gov Archive Site
MR blockade improves renovascular function in subjects with T2DM [ Time Frame: two and six months ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
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 receptor blockers. This study will test the hypothesis that 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 subjects 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 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: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
  • Type 2 Diabetes Mellitus
  • Vascular Disease
  • Drug: Spironolactone
    25 mg daily
  • Drug: hydrochlorothiazide + potassium
    12.5 mg hydrochlorothiazide daily plus 10mEq potassium
  • Other: placebo
    placebo capsule
  • Experimental: 1
    MR blockade (Spironolactone)
    Intervention: Drug: Spironolactone
  • Active Comparator: 2
    hydrochlorothiazide + potassium
    Intervention: Drug: hydrochlorothiazide + potassium
  • Placebo Comparator: 3
    placebo capsule
    Intervention: Other: placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
93
June 2013
January 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 > 8.5%, *
  • gout (If not already taking HCTZ),
  • the use of Rosiglitazone,**
  • 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 BP >160 mm Hg and diastolic BP >100 mm Hg,*
  • use of cyclic hormone replacement therapy
  • past intolerance of ACE inhibitor therapy
  • other major medical illnesses. Subjects with evidence of a previous myocardial infarction on the first adenosine-stimulated PET study will be withdrawn from the study.
  • Screening systolic blood pressure < 105 mm Hg off of anti-hypertensive medications

    • Subjects 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.

      • Subjects who are currently taking these medications will not qualify for a screening visit. If medications were recently stopped by the subject's physician, he or she may be screened but the baseline assessment protocol must occur 3 months after stopping.
Both
18 Years to 70 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00865124
2007-P-000564, 1 R01HL 087060-01A2
Yes
Gail Kurr Adler, Brigham and Women's Hospital
Brigham and Women's Hospital
National Institutes of Health (NIH)
Principal Investigator: Gail K Adler, MD, PhD Brigham and Women's Hospital
Brigham and Women's Hospital
July 2013

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