Cardiomyopathy in DMD: Lisinopril vs. Losartan

Cardiomyopathy Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01982695
• Other study ID #: IRB12-00149
• Status: Completed
• Phase: N/A
• First received: October 29, 2013
• Last updated: November 5, 2013
• Start date: March 2009
• Est. completion date: September 2013

Study information

• Verified date: November 2013
• Source: Nationwide Children's Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: September 2013
• Est. primary completion date: August 2012
• Accepts healthy volunteers: No
• Gender: Male
• Age group: N/A and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy
• Duchenne Muscular Dystrophy (DMD)
• Muscular Dystrophies
• Muscular Dystrophy, Duchenne

Intervention

Drug:
• Losartan

• Lisinopril

Locations

Country	Name	City	State
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	University of California Davis	Davis	California
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	St. Louis Children's Hospital	St. Louise	Missouri
United States	University of Minnesota	St. Paul	Minnesota

Sponsors (6)

Lead Sponsor	Collaborator
Nationwide Children's Hospital	Children's Hospital Boston, St. Louis Children's Hospital, University of California, Davis, University of Minnesota - Clinical and Translational Science Institute, Unverisity of Kansas Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pulmonary function testing	Forced vital capacity (FVC) will be measured using a spirometer. Participants will have a measurement collected at their baseline visit and then again at their 1 and 2 year visits.	Every 12 months for 2 years	No
Other	Changes in activities of daily living	Measured using the Egen Klassification (EK) Scale. Participants will have a measurement collected at their baseline visit and then again at their 1 and 2 year visits.	Every 12 months for 2 years	No
Other	Health related quality of life	Measured using the PedsQL. Participants will have a measurement collected at their baseline visit and then again at their 1 and 2 year visits.	Every 12 months for 2 years	No
Primary	Cardiac ejection fraction as measured by echocardiogram	Participants will have a baseline visit and then followed every four months for the duration study, anticipated for a total of 2 years.	Every 4 months for 2 years	Yes
Secondary	Skeletal muscle strength	Muscle strength will be measured by hand held dynamometer. Participants will have a measurement collected at their baseline visit and then again at their 1 and 2 year visits.	Every 12 months for 2 years	No
Secondary	Skeletal Muscle function	Skeletal muscle function will be measured by Brooke Upper Extremity Functional Rating Scale, Nine-Hole-Peg test, and 6-minute walk test (6MWT). Participants will have a measurement collected at their baseline visit and then again at their 1 and 2 year visits.	Every 12 months for 2 years	No

External Links

•   Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital
•   The Muscular Dystrophy Association