Clinical trial NCT01982695: Cardiomyopathy in DMD: Lisinopril vs. Losartan
Official title: 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: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Duchenne Muscular Dystrophy (DMD)
Cardiomyopathy
Keywords: Duchenne muscular Dystrophy (DMD)
Cardiomyopathy
Losartan
Lisinopril
Lead sponsor: Nationwide Children's Hospital
Sponsor class: OTHER
Collaborators: name: Boston Children's Hospital
name: University of California, Davis
name: Unverisity of Kansas Medical Center
name: University of Minnesota
name: St. Louis Children's Hospital
First posted: 2013-11-13
Enrollment: 23
Sex: MALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Cardiac Ejection Fraction as Measured by Echocardiogram
timeFrame: 12 month visit
Secondary outcomes:
Other outcomes:
Locations:
city: Davis
country: United States
facility: University of California Davis
state: California
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: St. Paul
country: United States
facility: University of Minnesota
state: Minnesota
city: St. Louise
country: United States
facility: St. Louis Children's Hospital
state: Missouri
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
Study officials:
References:
citation: 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.
citation: 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.
citation: Allen HD, Flanigan KM, Thrush PT, Dvorchik I, Yin H, Canter C, Connolly AM, Parrish M, McDonald CM, Braunlin E, Colan SD, Day J, Darras B, Mendell JR. A randomized, double-blind trial of lisinopril and losartan for the treatment of cardiomyopathy in duchenne muscular dystrophy. PLoS Curr. 2013 Dec 12;5:ecurrents.md.2cc69a1dae4be7dfe2bcb420024ea865. doi: 10.1371/currents.md.2cc69a1dae4be7dfe2bcb420024ea865.