Cardiomyopathy in DMD: Lisinopril vs. Losartan

Overview

This trial is a double-blind randomized clinical trial of lisinopril versus losartan for the treatment of cardiomyopathy in Duchenne Muscular Dystrophy (DMD). Both drugs are known to be effective for the treatment of dilated cardiomyopathy. ACEi have been reported to delay the onset and progression of left ventricle dysfunction in children with DMD. Multiple studies show therapeutic efficacy of losartan in animals with cardiomyopathy related to muscular dystrophy and in patients with cardiomyopathy from diverse causes. ARBs are often reserved for patients in whom heart failure is not adequately treated or where side effects preclude the use of an ACEi. However, in DMD, losartan might be a better choice as a first line drug because of studies demonstrating a potential benefit for skeletal muscle in the mdx mouse. Considering that both skeletal and cardiac muscles are major contributors of the disability of DMD, a drug that could improve both heart and skeletal muscles simultaneously would need consideration as the drug of choice for the cardiomyopathic DMD patient.

Full Title of Study: “Compare Efficacy of the Angiotensin Converting Enzyme Inhibitor (ACEi) Lisinopril With Angiotensin II Receptor Antagonist Losartan (ARB) for the Cardiomyopathy of Duchenne Muscular Dystrophy”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: August 2012

Interventions

  • Drug: Losartan
  • Drug: Lisinopril

Arms, Groups and Cohorts

  • Active Comparator: Lisinopril
  • Active Comparator: Losartan

Clinical Trial Outcome Measures

Primary Measures

  • Cardiac Ejection Fraction as Measured by Echocardiogram
    • Time Frame: 12 month visit
    • Mean cardiac ejection fraction as measured by echocardiogram at 12 month study visit. Cardiac ejection fractions were measured using the biplane Simpson’s rule using images obtained from the apical 4 chamber views of the heart.

Participating in This Clinical Trial

Inclusion Criteria

  • Duchenne muscular dystrophy patients of all ages – Null mutation of the dystrophin gene or muscle with <5% dystrophin – Doppler echocardiogram with ejection fraction (EF) <55% within 30 days of enrollment – Ability to cooperate for testing – Glucocorticoid treatment acceptable including daily or weekend administration of prednisone or deflazacort Exclusion Criteria:

  • Patients with EF 55% or greater – Patients with EF <40% after washout – Patients taking >5 mg lisinopril, or >25 mg losartan or >5 mg enalapril – Skeletal deformities or pulmonary anatomical variants that preclude consistent measures of Doppler echocardiography

Gender Eligibility: Male

Minimum Age: N/A

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Nationwide Children’s Hospital
  • Collaborator
    • Boston Children’s Hospital
  • Provider of Information About this Clinical Study
    • Principal Investigator: Jerry R. Mendell, Director, Center for Gene Therapy – Nationwide Children’s Hospital

References

Thrush PT, Allen HD, Viollet L, Mendell JR. Re-examination of the electrocardiogram in boys with Duchenne muscular dystrophy and correlation with its dilated cardiomyopathy. Am J Cardiol. 2009 Jan 15;103(2):262-5. doi: 10.1016/j.amjcard.2008.08.064. Epub 2008 Oct 30.

Citations Reporting on Results

Viollet L, Thrush PT, Flanigan KM, Mendell JR, Allen HD. Effects of angiotensin-converting enzyme inhibitors and/or beta blockers on the cardiomyopathy in Duchenne muscular dystrophy. Am J Cardiol. 2012 Jul 1;110(1):98-102. doi: 10.1016/j.amjcard.2012.02.064. Epub 2012 Mar 29.

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.