Cardiomyopathy in DMD: Lisinopril vs. Losartan

This study has been completed.
Sponsor:
Collaborators:
Children's Hospital Boston
University of California, Davis
Unverisity of Kansas Medical Center
University of Minnesota - Clinical and Translational Science Institute
St. Louis Children's Hospital
Information provided by (Responsible Party):
Jerry R. Mendell, Nationwide Children's Hospital
ClinicalTrials.gov Identifier:
NCT01982695
First received: October 29, 2013
Last updated: November 5, 2013
Last verified: November 2013
  Purpose

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 Intervention
Duchenne Muscular Dystrophy (DMD)
Cardiomyopathy
Drug: Losartan
Drug: Lisinopril

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Nationwide Children's Hospital:

Primary Outcome Measures:
  • Cardiac ejection fraction as measured by echocardiogram [ Time Frame: Every 4 months for 2 years ] [ Designated as safety issue: Yes ]
    Participants will have a baseline visit and then followed every four months for the duration study, anticipated for a total of 2 years.


Secondary Outcome Measures:
  • Skeletal muscle strength [ Time Frame: Every 12 months for 2 years ] [ Designated as safety issue: No ]
    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.

  • Skeletal Muscle function [ Time Frame: Every 12 months for 2 years ] [ Designated as safety issue: No ]
    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.


Other Outcome Measures:
  • Pulmonary function testing [ Time Frame: Every 12 months for 2 years ] [ Designated as safety issue: No ]
    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.

  • Changes in activities of daily living [ Time Frame: Every 12 months for 2 years ] [ Designated as safety issue: No ]
    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.

  • Health related quality of life [ Time Frame: Every 12 months for 2 years ] [ Designated as safety issue: No ]
    Measured using the PedsQL. Participants will have a measurement collected at their baseline visit and then again at their 1 and 2 year visits.


Enrollment: 17
Study Start Date: March 2009
Study Completion Date: September 2013
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Lisinopril Drug: Lisinopril
Active Comparator: Losartan Drug: Losartan

  Eligibility

Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01982695

Locations
United States, California
University of California Davis
Davis, California, United States
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States
United States, Massachusetts
Boston Children's Hospital
Boston, Massachusetts, United States
United States, Minnesota
University of Minnesota
St. Paul, Minnesota, United States
United States, Missouri
St. Louis Children's Hospital
St. Louise, Missouri, United States
United States, Ohio
Nationwide Children's Hospital
Columbus, Ohio, United States
Sponsors and Collaborators
Nationwide Children's Hospital
Children's Hospital Boston
University of California, Davis
Unverisity of Kansas Medical Center
University of Minnesota - Clinical and Translational Science Institute
St. Louis Children's Hospital
  More Information

Additional Information:
Publications:
Responsible Party: Jerry R. Mendell, Director, Center for Gene Therapy, Nationwide Children's Hospital
ClinicalTrials.gov Identifier: NCT01982695     History of Changes
Other Study ID Numbers: IRB12-00149
Study First Received: October 29, 2013
Last Updated: November 5, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Nationwide Children's Hospital:
Duchenne muscular Dystrophy (DMD)
Cardiomyopathy
Losartan
Lisinopril

Additional relevant MeSH terms:
Muscular Dystrophies
Cardiomyopathies
Muscular Dystrophy, Duchenne
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Heart Diseases
Cardiovascular Diseases
Genetic Diseases, X-Linked
Losartan
Lisinopril
Angiotensin-Converting Enzyme Inhibitors
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Protease Inhibitors
Enzyme Inhibitors
Cardiotonic Agents
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 22, 2014