Role of Mineralocorticoid Receptor in Diabetic Cardiovascular Disease

Type 2 Diabetes Mellitus Clinical Trial

Official title:

Role of Mineralocorticoid Receptor in Diabetic Cardiovascular Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00865124
• Other study ID #: 2007-P-000564
• Secondary ID: 1R01HL087060-01A
• Status: Completed
• Phase: N/A
• First received: March 17, 2009
• Last updated: July 31, 2013
• Start date: September 2008
• Est. completion date: June 2013

Study information

• Verified date: July 2013
• Source: Brigham and Women's Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 93
• Est. completion date: June 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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.

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus
• Vascular Disease
• Vascular Diseases

Intervention

Drug:
• Spironolactone
25 mg daily
• hydrochlorothiazide + potassium
12.5 mg hydrochlorothiazide daily plus 10mEq potassium

Other:
• placebo
placebo capsule

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Brigham and Women's Hospital	National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MR blockade improves coronary circulatory and cardiac diastolic function in individuals with T2DM		two and six months	No
Secondary	MR blockade improves renovascular function in subjects with T2DM		two and six months	No