Eplerenone for Subclinical Cardiomyopathy in Duchenne Muscular Dystrophy (E-SCAR DMD)

• ClinicalTrials.gov Identifier: NCT01521546
• Recruitment Status: Completed
• First Posted: January 30, 2012
• Results First Posted: May 27, 2015
• Last Update Posted: November 8, 2016
• Sponsor: Subha Raman
• Collaborator: Ballou Skies
• Information provided by (Responsible Party): Subha Raman, Ohio State University

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Duchenne Muscular Dystrophy	Drug: eplerenone; Drug: placebo	Not Applicable

Detailed 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 42 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Early Treatment With Aldosterone Antagonism Attenuates Cardiomyopathy in Duchenne Muscular Dystrophy
• Study Start Date: February 2012
• Actual Primary Completion Date: June 2016
• Actual Study Completion Date: June 2016

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: eplerenone; active study drug	Drug: eplerenone; 25mg tablet, once daily by mouth for 12 months
Placebo Comparator: sugar pill; placebo	Drug: placebo; one tablet by mouth daily for 12 months

Outcome Measures

Primary Outcome Measures :

1. 12-month Change in Myocardial Strain [ Time Frame: baseline and 12 months ]
   a sensitive measurement of heart function using cardiac MRI, change was 12 months minus baseline.

Eligibility Criteria

• Ages Eligible for Study: 7 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, California

Mattel Children's Hospital and David Geffen School of Medicine at UCLA

Los Angeles, California, United States, 90095-1743

United States, Ohio

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

The Ohio State University Medical Center

Columbus, Ohio, United States, 43210

Sponsors and Collaborators

Subha Raman

Ballou Skies

Investigators

• Principal Investigator: Subha V Raman, MD, MSEE; Ohio State University

More Information

Additional Information:

Journal article 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Raman SV, Hor KN, Mazur W, He X, Kissel JT, Smart S, McCarthy B, Roble SL, Cripe LH. Eplerenone for early cardiomyopathy in Duchenne muscular dystrophy: results of a two-year open-label extension trial. Orphanet J Rare Dis. 2017 Feb 20;12(1):39. doi: 10.1186/s13023-017-0590-8.

Raman SV, Hor KN, Mazur W, Halnon NJ, Kissel JT, He X, Tran T, Smart S, McCarthy B, Taylor MD, Jefferies JL, Rafael-Fortney JA, Lowe J, Roble SL, Cripe LH. Eplerenone for early cardiomyopathy in Duchenne muscular dystrophy: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2015 Feb;14(2):153-61. doi: 10.1016/S1474-4422(14)70318-7. Epub 2014 Dec 30. Erratum in: Lancet Neurol. 2015 Feb;14(2):135.

• Responsible Party: Subha Raman, Professor of Medicine, Ohio State University
• ClinicalTrials.gov Identifier: NCT01521546
• Other Study ID Numbers: 2011H0251
• First Posted: January 30, 2012
• Results First Posted: May 27, 2015
• Last Update Posted: November 8, 2016
• Last Verified: October 2016

Keywords provided by Subha Raman, Ohio State University:

Duchenne muscular dystrophy; cardiomyopathy; aldosterone antagonist

Additional relevant MeSH terms:

Muscular Dystrophies; Muscular Dystrophy, Duchenne; Cardiomyopathies; Heart Diseases; Cardiovascular Diseases; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Eplerenone; Mineralocorticoid Receptor Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Diuretics, Potassium Sparing; Diuretics; Natriuretic Agents; Antihypertensive Agents