Cardiomyopathy in DMD: Lisinopril vs. Losartan

• Sponsor: Nationwide Children's Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT01982695
• Collaborator: Boston Children's Hospital (Other), University of California, Davis (Other), Unverisity of Kansas Medical Center (Other), University of Minnesota (Other), St. Louis Children's Hospital (Other)
• Enrollment: 23
• Locations: 6
• Arms: 2
• Duration (Months): 54
• Patients Per Site: 3.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Duchenne Muscular Dystrophy (DMD); Cardiomyopathy	Drug: Losartan; Drug: Lisinopril	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 23 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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 Start Date: Mar 1, 2009
• Actual Primary Completion Date: Aug 1, 2012
• Actual Study Completion Date: Sep 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Lisinopril	Drug: Lisinopril
Active Comparator: Losartan	Drug: Losartan

Outcome Measures

Primary Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: Male
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California Davis	Davis	California	United States
2	University of Kansas Medical Center	Kansas City	Kansas	United States
3	Boston Children's Hospital	Boston	Massachusetts	United States
4	University of Minnesota	St. Paul	Minnesota	United States
5	St. Louis Children's Hospital	St. Louise	Missouri	United States
6	Nationwide Children's Hospital	Columbus	Ohio	United States

Sponsors and Collaborators

• Nationwide Children's Hospital
• Boston Children's Hospital
• University of California, Davis
• Unverisity of Kansas Medical Center
• University of Minnesota
• St. Louis Children's Hospital

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

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

Publications

• 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.

• Responsible Party: Jerry R. Mendell, Director, Center for Gene Therapy, Nationwide Children's Hospital
• ClinicalTrials.gov Identifier: NCT01982695
• Other Study ID Numbers: IRB12-00149
• First Posted: Nov 13, 2013
• Last Update Posted: Mar 21, 2017
• Last Verified: Jan 1, 2017

• Keywords provided by Jerry R. Mendell, Director, Center for Gene Therapy, Nationwide Children's Hospital: Duchenne muscular Dystrophy (DMD); Cardiomyopathy; Losartan; Lisinopril
• Additional relevant MeSH terms: Muscular Dystrophies; Muscular Dystrophy, Duchenne; Cardiomyopathies; Losartan; Lisinopril

Study Results

Participant Flow

Arm/Group Title	Lisinopril	Losartan
Arm/Group Description	Approximately 0.07 mg/kg/day in oral capsules	Approximately 0.7 mg/kg/day in oral capsules
Period Title: Overall Study
STARTED	12	11
COMPLETED	12	10
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Lisinopril	Lospartan	Total
Arm/Group Description	Lisinopril	Lisinopril	Total of all reporting groups
Overall Participants	12	11	23
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	12.5	15.5	14
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	12 100%	11 100%	23 100%
Ejection Fraction (percentage of blood leaving the heart) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of blood leaving the heart]	47.5 (6.25)	47.7 (5.49)	47.6 (5.77)

Outcome Measures

1. Primary Outcome

Title	Cardiac Ejection Fraction as Measured by Echocardiogram
Description	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

Outcome Measure Data

Analysis Population Description

All patients that received a 12 month echocardiogram evaluation

Arm/Group Title	Lisinopril	Losartan
Arm/Group Description	Lisinopril	Losartan
Measure Participants	7	9
Mean (Standard Deviation) [percentage of blood leaving the heart]	54.6 (5.19)	55.2 (7.19)

Adverse Events

Arm/Group Title	Lisinopril		Losartan
Arm/Group Description	Lisinopril		Losartan
All Cause Mortality
	Lisinopril		Losartan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Lisinopril		Losartan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	Lisinopril		Losartan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		2/10 (20%)
Cardiac disorders
Cardiomyopathy	0/12 (0%)	0	1/10 (10%)	1
Skin and subcutaneous tissue disorders
Allergic reaction to medication	0/12 (0%)	0	1/10 (10%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.