NCT01982695

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
23

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Mar 2009

Longer than P75 for not_applicable

Geographic Reach
1 country

6 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 2009

Completed
3.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2012

Completed
1.1 years until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2013

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

October 29, 2013

Completed
15 days until next milestone

First Posted

Study publicly available on registry

November 13, 2013

Completed
3.4 years until next milestone

Results Posted

Study results publicly available

March 21, 2017

Completed
Last Updated

March 21, 2017

Status Verified

January 1, 2017

Enrollment Period

3.4 years

First QC Date

October 29, 2013

Results QC Date

August 14, 2015

Last Update Submit

January 31, 2017

Conditions

Keywords

Duchenne muscular Dystrophy (DMD)CardiomyopathyLosartanLisinopril

Outcome Measures

Primary Outcomes (1)

  • 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.

    12 month visit

Study Arms (2)

Lisinopril

ACTIVE COMPARATOR
Drug: Lisinopril

Losartan

ACTIVE COMPARATOR
Drug: Losartan

Interventions

Losartan
Lisinopril

Eligibility Criteria

Sexmale
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (6)

University of California Davis

Davis, California, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, United States

Location

Boston Children's Hospital

Boston, Massachusetts, United States

Location

University of Minnesota

Saint Paul, Minnesota, United States

Location

St. Louis Children's Hospital

Saint Louise, Missouri, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, United States

Location

Related Publications (3)

  • 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.

    PMID: 19121448BACKGROUND
  • 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.

  • 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.

Related Links

MeSH Terms

Conditions

Muscular Dystrophy, DuchenneCardiomyopathies

Interventions

LosartanLisinopril

Condition Hierarchy (Ancestors)

Muscular DystrophiesMuscular Disorders, AtrophicMuscular DiseasesMusculoskeletal DiseasesNeuromuscular DiseasesNervous System DiseasesGenetic Diseases, X-LinkedGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesHeart DiseasesCardiovascular Diseases

Intervention Hierarchy (Ancestors)

Biphenyl CompoundsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsImidazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsTetrazolesDipeptidesOligopeptidesPeptidesAmino Acids, Peptides, and Proteins

Results Point of Contact

Title
Dr. Jerry R. Mendell
Organization
Nationwide Children's Hopsital

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Director, Center for Gene Therapy

Study Record Dates

First Submitted

October 29, 2013

First Posted

November 13, 2013

Study Start

March 1, 2009

Primary Completion

August 1, 2012

Study Completion

September 1, 2013

Last Updated

March 21, 2017

Results First Posted

March 21, 2017

Record last verified: 2017-01

Locations