Cardiomyopathy, Duchenne Muscular Dystrophy (DMD)
Conditions
Keywords
Duchenne muscular Dystrophy (DMD), Cardiomyopathy, Losartan, Lisinopril
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.
Interventions
DRUGLosartan
DRUGLisinopril
Sponsors
Boston Children's Hospital
University of California, Davis
University of Kansas Medical Center
University of Minnesota
St. Louis Children's Hospital
Nationwide Children's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cardiac Ejection Fraction as Measured by Echocardiogram | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lisinopril Lisinopril | 12 |
| Lospartan Lisinopril | 11 |
| Total | 23 |
Baseline characteristics
| Characteristic | Lisinopril | Lospartan | Total |
|---|---|---|---|
| Age, Continuous | 12.5 years | 15.5 years | 14 years |
| Ejection Fraction | 47.5 percentage of blood leaving the heart STANDARD_DEVIATION 6.25 | 47.7 percentage of blood leaving the heart STANDARD_DEVIATION 5.49 | 47.6 percentage of blood leaving the heart STANDARD_DEVIATION 5.77 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 12 Participants | 11 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 12 | 2 / 10 |
| serious Total, serious adverse events | 0 / 12 | 0 / 10 |
Outcome results
Primary
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.
Time frame: 12 month visit
Population: All patients that received a 12 month echocardiogram evaluation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lisinopril | Cardiac Ejection Fraction as Measured by Echocardiogram | 54.6 percentage of blood leaving the heart | Standard Deviation 5.19 |
| Losartan | Cardiac Ejection Fraction as Measured by Echocardiogram | 55.2 percentage of blood leaving the heart | Standard Deviation 7.19 |