Aldosterone and Vascular Disease in Diabetes Mellitus
Information source: Brigham and Women's Hospital
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Diabetes Mellitus; Endothelial Dysfunction; Albuminuria
Intervention: eplerenone (Drug); Hydrochlorothiazide (Drug)
Phase: N/A
Status: Completed
Sponsored by: Brigham and Women's Hospital Official(s) and/or principal investigator(s): Gail K Adler, MD, PhD, Principal Investigator, Affiliation: Brigham and Women's Hospital Boston, MA
Summary
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).
Clinical Details
Official title: Aldosterone and Vascular Disease in Diabetes Mellitus
Study design: Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double-Blind, Primary Purpose: Treatment
Primary outcome: Coronary microvascular function assessed by myocardial perfusion reserve measured by MRI
Secondary outcome: Endothelial dysfunction assessed by brachial artery reactivityInflammation and cellular oxidative stress and injury, assessed by CRP, MCP-1, PAI-1, nephrin, cystanin C, F2 isoprostanes, and urinary 12-HETE Proteinuria
Detailed description:
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.
Eligibility
Minimum age: 21 Years.
Maximum age: 64 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
Men and women (21-64 years old) with type 1 or type 2 diabetes mellitus and albuminuria
(over 30 mg/g creatinine).
Exclusion Criteria:
Exclusion criteria include: (1) subjects without hypertension who have baseline systolic
blood pressure <100 mmHg, (2) severe hypertension (blood pressure must be well-controlled
on 3 antihypertensive agents or <150/100 mmHg on £2 antihypertensive agents), (3)
ischemic changes on resting electrocardiogram, (4) clinical evidence of heart disease,
cerebrovascular or peripheral vascular disease, (5) significant cardiac arrhythmias, (6)
aortic stenosis, (7) 2nd or 3rd degree atrio-ventricular block, sinus node disease, or
symptomatic bradycardia, (8) bronchospastic lung disease with active wheezing, (9) known
hypersensitivity to any of the study drugs, (10) any contraindication to MRI, (11) serum
creatinine ³ 1. 5 mg/dL, (12) serum potassium ³ 5. 0 mmol/L, (13) current smoker, (14) Serum
transaminases greater than twice the upper limit of normal, (15) a history of gout, (16)
pregnancy, and (17) other active medical problems detected by examination or laboratory
testing.
Locations and Contacts
Brigham and Women's Hospital, Boston, Massachusetts 02115, United States
Additional Information
Starting date: August 2003
Last updated: December 28, 2007
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