Early Treatment of Cardiomyopathy in Duchenne Muscular Dystrophy

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: November 20, 2013
Last verified: November 2013

January 26, 2012
November 20, 2013
February 2012
July 2014   (final data collection date for primary outcome measure)
myocardial strain [ Time Frame: 1 year ] [ Designated as safety issue: No ]
a sensitive measurement of heart function using cardiac MRI
Same as current
Complete list of historical versions of study NCT01521546 on ClinicalTrials.gov Archive Site
collagen turnover [ Time Frame: 1 yr ] [ Designated as safety issue: No ]
a measurement of collagen turnover in the blood
Same as current
Not Provided
Not Provided
 
Early Treatment of Cardiomyopathy in Duchenne Muscular Dystrophy
Early Treatment With Aldosterone Antagonism Attenuates Cardiomyopathy in Duchenne Muscular Dystrophy

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.

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.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Duchenne Muscular Dystrophy
  • Drug: eplerenone
    25mg tablet, once daily by mouth for 12 months
  • Drug: placebo
    one tablet by mouth daily for 12 months
  • Active Comparator: eplerenone
    active study drug
    Intervention: Drug: eplerenone
  • Placebo Comparator: sugar pill
    placebo
    Intervention: Drug: placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
40
March 2015
July 2014   (final data collection date for primary outcome measure)

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
Male
7 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01521546
2011H0251
Yes
Subha Raman, The Ohio State University
Subha Raman
Ballou Skies
Principal Investigator: Subha V Raman, MD, MSEE Ohio State University
Ohio State University
November 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP