Role of Mineralocorticoid Receptor in Diabetic Cardiovascular Disease

NCT ID: NCT00865124

Last Updated: 2017-06-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 69 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-09-30
• Study Completion Date: 2014-05-31

Brief 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 (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.

Conditions

Type 2 Diabetes Mellitus; Vascular Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Spironolactone (mineralocorticoid receptor [MR] blockade)

Group Type: EXPERIMENTAL

Spironolactone

Intervention Type: DRUG

25 mg capsule daily for 6 months

Hydrochlorothiazide + potassium

Group Type: ACTIVE_COMPARATOR

Hydrochlorothiazide + potassium

Intervention Type: DRUG

hydrochlorothiazide (HCTZ) + potassium, 12.5 mg/10 milliequivalents (mEq) capsule daily

Placebo capsule

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo capsule daily

Interventions

Spironolactone

25 mg capsule daily for 6 months

Intervention Type: DRUG

Hydrochlorothiazide + potassium

hydrochlorothiazide (HCTZ) + potassium, 12.5 mg/10 milliequivalents (mEq) capsule daily

Intervention Type: DRUG

Placebo

Placebo capsule daily

Intervention Type: OTHER

Eligibility 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 (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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Gail Kurr Adler

Associate Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Gail K Adler, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Locations

Brigham and Women's Hospital

Boston, Massachusetts, United States

Countries

United States

References

Haas AV, Rosner BA, Kwong RY, Rao AD, Garg R, Di Carli MF, Adler GK. Sex Differences in Coronary Microvascular Function in Individuals With Type 2 Diabetes. Diabetes. 2019 Mar;68(3):631-636. doi: 10.2337/db18-0650. Epub 2018 Nov 8.

Reference Type: DERIVED

PMID: 30409780 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25125488 (View on PubMed)

Other Identifiers

1R01HL087060-01A2

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2007-P-000564

Identifier Type: -

Identifier Source: org_study_id