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
  Purpose

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.


Condition Intervention
Type 2 Diabetes Mellitus
Vascular Disease
Drug: Spironolactone
Drug: hydrochlorothiazide + potassium
Other: placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Role of Mineralocorticoid Receptor in Diabetic Cardiovascular Disease

Resource links provided by NLM:


Further study details as provided by Brigham and Women's Hospital:

Primary Outcome Measures:
  • MR blockade improves coronary circulatory and cardiac diastolic function in individuals with T2DM [ Time Frame: two and six months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • MR blockade improves renovascular function in subjects with T2DM [ Time Frame: two and six months ] [ Designated as safety issue: No ]

Enrollment: 93
Study Start Date: September 2008
Study Completion Date: June 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
MR blockade (Spironolactone)
Drug: Spironolactone
25 mg daily
Active Comparator: 2
hydrochlorothiazide + potassium
Drug: hydrochlorothiazide + potassium
12.5 mg hydrochlorothiazide daily plus 10mEq potassium
Placebo Comparator: 3
placebo capsule
Other: placebo
placebo capsule

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00865124

Locations
United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Brigham and Women's Hospital
Investigators
Principal Investigator: Gail K Adler, MD, PhD Brigham and Women's Hospital
  More Information

No publications provided

Responsible Party: Gail Kurr Adler, Associate Professor of Medicine, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT00865124     History of Changes
Other Study ID Numbers: 2007-P-000564, 1 R01HL 087060-01A2
Study First Received: March 17, 2009
Last Updated: July 31, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Cardiovascular Diseases
Diabetes Mellitus
Diabetes Mellitus, Type 2
Vascular Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Hydrochlorothiazide
Spironolactone
Mineralocorticoids
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Sodium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Aldosterone Antagonists
Hormone Antagonists

ClinicalTrials.gov processed this record on July 29, 2014