Eplerenone for Subclinical Cardiomyopathy in Duchenne Muscular Dystrophy

Duchenne Muscular Dystrophy Clinical Trial

— E-SCAR DMD  

Official title:

Early Treatment With Aldosterone Antagonism Attenuates Cardiomyopathy in Duchenne Muscular Dystrophy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01521546
• Other study ID #: 2011H0251
• Status: Active, not recruiting
• Phase: N/A
• First received: January 26, 2012
• Last updated: June 26, 2015
• Start date: February 2012
• Est. completion date: July 2016

Study information

• Verified date: June 2015
• Source: Ohio State University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

Duchenne muscular dystrophy (DMD), the most common muscular dystrophy, leads to skeletal and cardiac muscle damage. Treatment of pulmonary complications has improved survival; however, heart muscle disease or cardiomyopathy has emerged as a leading cause of death, typically by the third decade. Although myocardial changes begin early, clinically significant heart disease is rarely detected in the first decade of life. Consequently, DMD cardiomyopathy frequently goes unrecognized (and untreated) until advanced (and irreversible).

Current DMD cardiovascular care guidelines recommend beta-blockers and angiotensin converting enzyme inhibitors (ACEIs) when decreased ejection fraction (EF) is noted by echocardiography (echo); however, this strategy has not significantly improved outcomes. Our team has recently made a breakthrough in a mouse study, showing in a model that causes the same heart muscle disease in humans with DMD adding an old medicine traditionally used for high blood pressure and late-stage heart failure can actually prevent heart muscle damage. Because of this drug's proven safety in both children and adults, it is ready to be studied immediately in an RCT in patients with DMD to hopefully show, as we did in mice, that we can prevent the devastating consequences of heart muscle damage.

Description:

Duchenne Muscular dystrophy (DMD) is a deadly X-linked disease affecting 1 in 3,500 males. DMD patients suffer significant disability due to skeletal myopathy and excess death due to cardiomyopathy. Current guidelines advocate initiating cardioprotective treatment with evident global cardiac dysfunction, yet this treatment paradigm has not improved survival much beyond the third decade of life. Potentially promising approaches like gene therapy will take considerable time to improve outcomes. Recently completed studies in a DMD mouse model at our institution indicate that existing drugs known as aldosterone antagonists, typically reserved for advanced heart failure patients, preserve skeletal and cardiac muscle function at 80% of normal. Clinical studies at many centers including ours have shown that high-resolution, noninvasive cardiac magnetic resonance (CMR) detects subclinical myocardial fibrosis and abnormal regional function prior to global functional abnormalities. Combining findings from these preclinical and clinical studies, we plan to execute a randomized, controlled clinical trial (RCT) of eplerenone plus background therapy vs. background therapy alone in patients with DMD. We expect that the aldosterone antagonist eplerenone compared to standard therapy significantly delays progressive cardiomyopathy and skeletal myopathy using highly reproducible imaging biomarkers selected for efficient sample size design, to ultimately reduce disability and death.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 42
• Est. completion date: July 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 7 Years and older

Eligibility

Inclusion Criteria:

• DMD patients age 7 years and older (and able to complete cardiac MRI without sedation) with preserved left ventricular (LV) systolic function and abnormal heart muscle by late post-gadolinium imaging (LGE)

Exclusion Criteria:

• renal insufficiency (GFR <40 mL/min/m2)

• non-MR compatible implants (e.g. neurostimulator, AICD)

• severe claustrophobia

• allergy to gadolinium contrast

• prior use of or known allergy to epleronone

• use of potassium-sparing diuretics

• serum potassium level of >5.0 mmol/L

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardiomyopathies
• Duchenne Muscular Dystrophy
• Muscular Dystrophies
• Muscular Dystrophy, Duchenne

Intervention

Drug:
• eplerenone
25mg tablet, once daily by mouth for 12 months
• placebo
one tablet by mouth daily for 12 months

Locations

Country	Name	City	State
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	The Ohio State University Medical Center	Columbus	Ohio
United States	Mattel Children's Hospital and David Geffen School of Medicine at UCLA	Los Angeles	California

Sponsors (2)

Lead Sponsor	Collaborator
Subha Raman	Ballou Skies

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	12-month Change in Myocardial Strain	a sensitive measurement of heart function using cardiac MRI, change was 12 months minus baseline.	baseline and 12 months	No

External Links

•   Journal article