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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Ballou Skies
Information provided by (Responsible Party):
Subha Raman, The Ohio State University
ClinicalTrials.gov Identifier:
NCT01521546
First received: January 26, 2012
Last updated: June 27, 2014
Last verified: June 2014
  Purpose

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 Intervention
Duchenne Muscular Dystrophy
Drug: eplerenone
Drug: placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Early Treatment With Aldosterone Antagonism Attenuates Cardiomyopathy in Duchenne Muscular Dystrophy

Resource links provided by NLM:


Further study details as provided by Ohio State University:

Primary Outcome Measures:
  • myocardial strain [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    a sensitive measurement of heart function using cardiac MRI


Secondary Outcome Measures:
  • collagen turnover [ Time Frame: 1 yr ] [ Designated as safety issue: No ]
    a measurement of collagen turnover in the blood


Estimated Enrollment: 42
Study Start Date: February 2012
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   7 Years and older
Genders 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01521546

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

No publications provided

Responsible Party: Subha Raman, Professor of Medicine, The Ohio State University
ClinicalTrials.gov Identifier: NCT01521546     History of Changes
Other Study ID Numbers: 2011H0251
Study First Received: January 26, 2012
Last Updated: June 27, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Ohio State University:
Duchenne muscular dystrophy
cardiomyopathy
aldosterone antagonist

Additional relevant MeSH terms:
Muscular Dystrophy, Duchenne
Cardiomyopathies
Muscular Dystrophies
Cardiovascular Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Heart Diseases
Muscular Diseases
Muscular Disorders, Atrophic
Musculoskeletal Diseases
Nervous System Diseases
Neuromuscular Diseases
Eplerenone
Cardiovascular Agents
Diuretics
Diuretics, Potassium Sparing
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Mineralocorticoid Receptor Antagonists
Natriuretic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014