Aldosterone and Vascular Disease in Diabetes Mellitus

NCT ID: NCT00214825

Last Updated: 2008-01-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

46 participants

Study Classification

INTERVENTIONAL

Study Start Date

2003-08-31

Study Completion Date

2006-03-31

Brief Summary

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Specific aims for this proposal are to determine in patients with diabetes mellitus the effects of an aldosterone receptor antagonist on:

1. Coronary microvascular function assessed by MRI perfusion reserve,
2. Endothelial dysfunction assessed by brachial artery reactivity studies, and
3. Inflammation assessed by blood measurements of c-reactive protein (CRP), monocyte chemoattractant protein-1 (MCP-1), and plasminogen activator inhibitor-1 (PAI-1).

Detailed Description

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Recent human and animal studies suggest that activation of the mineralocorticoid receptor (MR) by aldosterone, the final product of the renin-angiotensin-aldosterone system, causes microvascular damage, vascular inflammation, and endothelial dysfunction. Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are unable to provide long-term aldosterone suppression. Therefore, we hypothesize that activation of the MR contributes to progression of vascular disease in patients with diabetes already using ACE inhibitor therapy.

Specific aims for this proposal are to determine in patients with type 1 or type 2 diabetes mellitus and proteinuria, already receiving ACE inhibitor or ARB therapy, the effects of an aldosterone receptor antagonist vs. hydrochlorothiazide on:

1. Coronary microvascular function assessed by MRI perfusion reserve,
2. Endothelial dysfunction assessed by brachial artery reactivity studies,
3. Inflammation and cellular oxidative stress and injury, assessed by c-reactive protein (CRP), MCP-1, plasminogen activator inhibitor-1 (PAI-1).
4. Proteinuria and whether there is a differential effect when a MR antagonist or HCTZ is added to the ACE inhibitor therapy.

This is a double-blind, randomized, cross-over study of men and women (21-64 years old) with type 1 or type 2 diabetes mellitus and albuminuria (³30 mg/g creatinine). Participants will be randomized to a MR antagonist + placebo or HCTZ + potassium supplementation for 6 weeks. The MR antagonist arm will receive eplerenone 50 mg daily. The HCTZ arm will receive HCTZ 12.5 mg with potassium 10 Meq daily. Amlodipine 5 to 10 mg daily will be added during run phase to control blood pressure. Blood pressure goal is less than 130/80 mm Hg. There will be a 4-week washout period before the patients are crossed-over to the other study arm. MRI perfusion reserve, brachial artery reactivity, and blood samples will be obtained at the beginning and end of each treatment arm.

Conditions

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Diabetes Mellitus Endothelial Dysfunction Albuminuria

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Study Groups

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1

MR antagonist (Eplerenone) + placebo

Group Type EXPERIMENTAL

eplerenone

Intervention Type DRUG

50 mg daily for 6 weeks with placebo

2

Hydrochlorothiazide plus potassium

Group Type PLACEBO_COMPARATOR

Hydrochlorothiazide

Intervention Type DRUG

HCTZ 12.5 mg with potassium (10 mEq) daily for 6 weeks

Interventions

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eplerenone

50 mg daily for 6 weeks with placebo

Intervention Type DRUG

Hydrochlorothiazide

HCTZ 12.5 mg with potassium (10 mEq) daily for 6 weeks

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

Men and women (21-64 years old) with type 1 or type 2 diabetes mellitus and albuminuria (over 30 mg/g creatinine).
Minimum Eligible Age

21 Years

Maximum Eligible Age

64 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institutes of Health (NIH)

NIH

Sponsor Role collaborator

Brigham and Women's Hospital

OTHER

Sponsor Role lead

Responsible Party

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Brigham and Women's Hospital

Principal Investigators

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Gail K Adler, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital Boston, MA

Locations

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Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status

Countries

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United States

References

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Joffe HV, Kwong RY, Gerhard-Herman MD, Rice C, Feldman K, Adler GK. Beneficial effects of eplerenone versus hydrochlorothiazide on coronary circulatory function in patients with diabetes mellitus. J Clin Endocrinol Metab. 2007 Jul;92(7):2552-8. doi: 10.1210/jc.2007-0393. Epub 2007 May 8.

Reference Type RESULT
PMID: 17488800 (View on PubMed)

Other Identifiers

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2003-P-001273 BWH

Identifier Type: -

Identifier Source: org_study_id

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