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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01521546
First Posted: January 30, 2012
Last Update Posted: November 8, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Ballou Skies
Information provided by (Responsible Party):
Subha Raman, The Ohio State University
  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
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

Resource links provided by NLM:


Further study details as provided by Subha Raman, The Ohio State University:

Primary Outcome Measures:
  • 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.


Enrollment: 42
Study Start Date: February 2012
Study Completion Date: June 2016
Primary Completion Date: June 2016 (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

Information from the National Library of Medicine

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Ages Eligible for Study:   7 Years and older   (Child, Adult, Senior)
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Subha Raman, Professor of Medicine, The Ohio State University
ClinicalTrials.gov Identifier: NCT01521546     History of Changes
Other Study ID Numbers: 2011H0251
First Submitted: January 26, 2012
First Posted: January 30, 2012
Results First Submitted: April 21, 2015
Results First Posted: May 27, 2015
Last Update Posted: November 8, 2016
Last Verified: October 2016

Keywords provided by Subha Raman, The Ohio State University:
Duchenne muscular dystrophy
cardiomyopathy
aldosterone antagonist

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