Role of Mineralocorticoid Receptor in Diabetic Cardiovascular Disease

NCT00865124 | Completed Results DMC

• 2 other identifiers: 2007-P-0005641R01HL087060-01A2
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 1

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

Conditions

Type 2 Diabetes Mellitus; Vascular Disease

Outcome Measures

Primary Outcomes (1)

• Change in Coronary Flow Reserve From Baseline to 6 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.

  Baseline and six months

Secondary Outcomes (3)

• Change in Mitral Annulus Velocities on Tissue Doppler (Delta E/e' Ratio), a Measure of Diastolic Function

  Baseline and six months

• Mitral Annulus Velocities on Tissue Doppler (Delta E/e' Ratio), a Measure of Diastolic Function (With Angiotensin II)

  Baseline and six months

• Change in Renal Plasma Flow

  Baseline and six months

Study Arms (3)

Spironolactone (mineralocorticoid receptor [MR] blockade)

EXPERIMENTAL

Drug: Spironolactone

Hydrochlorothiazide + potassium

ACTIVE COMPARATOR

Drug: Hydrochlorothiazide + potassium

Placebo capsule

PLACEBO COMPARATOR

Other: Placebo

Interventions

Spironolactone DRUG

25 mg capsule daily for 6 months

Spironolactone (mineralocorticoid receptor [MR] blockade)

Hydrochlorothiazide + potassium DRUG

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

Hydrochlorothiazide + potassium

Placebo OTHER

Placebo capsule daily

Placebo capsule

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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,
• nd 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,

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• National Institutes of Health (NIH): collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Related Publications (2)

• 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.

  PMID: 30409780 DERIVED

• 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.

  PMID: 25125488 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Vascular Diseases

Interventions

Spironolactone; Hydrochlorothiazide; Potassium

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Chlorothiazide; Benzothiadiazines; Sulfonamides; Sulfones; Sulfur Compounds; Thiazides; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Metals, Alkali; Elements; Inorganic Chemicals; Metals, Light; Metals

Results Point of Contact

• Title: Gail K. Adler
• Organization: Brigham and Women's Hospital

gadler@partners.org

617-732-5661

Study Officials

• Gail K Adler, MD, PhD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: March 17, 2009
• First Posted: March 19, 2009
• Study Start: September 1, 2008
• Primary Completion: August 1, 2013
• Study Completion: May 1, 2014
• Last Updated: June 14, 2017
• Results First Posted: June 14, 2017

Record last verified: 2017-05

Locations

US (1)