Overview

This trial is active, not recruiting.

Condition duchenne muscular dystrophy
Treatments eplerenone, placebo
Sponsor Subha Raman
Collaborator Ballou Skies
Start date February 2012
End date July 2014
Trial size 42 participants
Trial identifier NCT01521546, 2011H0251

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Active Comparator)
active study drug
eplerenone
25mg tablet, once daily by mouth for 12 months
(Placebo Comparator)
placebo
placebo
one tablet by mouth daily for 12 months

Primary Outcomes

Measure
myocardial strain
time frame: 1 year

Secondary Outcomes

Measure
collagen turnover
time frame: 1 yr

Eligibility Criteria

Male participants at least 7 years old.

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

Additional Information

Official title Early Treatment With Aldosterone Antagonism Attenuates Cardiomyopathy in Duchenne Muscular Dystrophy
Principal investigator Subha V Raman, MD, MSEE
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.
Trial information was received from ClinicalTrials.gov and was last updated in June 2014.
Information provided to ClinicalTrials.gov by Ohio State University.