Cardiomyopathy in DMD: Lisinopril vs. Losartan

Study Overview
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Brief Summary
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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.

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

Conditions
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Duchenne Muscular Dystrophy (DMD), Cardiomyopathy

Intervention / Treatment
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* Drug: Losartan
* Drug: Lisinopril


Participation Criteria
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Eligibility Criteria
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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
Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Lisinopril<br> | Drug: Lisinopril<br> <br> |
| Active Comparator: Losartan<br> | Drug: Losartan<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiac Ejection Fraction as Measured by Echocardiogram | 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. | 12 month visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Duchenne muscular Dystrophy (DMD), Cardiomyopathy, Losartan, Lisinopril