Safety Study of Mini-Dystrophin Gene to Treat Duchenne Muscular Dystrophy - Full Text View

Sponsor:	Nationwide Children's Hospital
Collaborator:	Asklepios Biopharmaceutical Inc.
Information provided by:	Nationwide Children's Hospital
ClinicalTrials.gov Identifier:	NCT00428935

Purpose

The purpose of this study is to determine the safety of a miniature dystrophin gene in the treatment of progressive muscle weakness due to Duchenne Muscular Dystrophy (DMD).

Condition	Intervention	Phase
Duchenne Muscular Dystrophy	Gene Transfer: rAAV vector expressing Mini-Dystrophin with CMV promoter	Phase I

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double-Blind, Placebo Control, Single Group Assignment, Safety Study
Official Title:	Phase 1 Clinical Trial of rAAV2.5-CMV-Mini-Dystrophin Gene Vector in Duchenne Muscular Dystrophy

Resource links provided by NLM:

Genetics Home Reference related topics: Duchenne and Becker muscular dystrophy L1 syndrome

MedlinePlus related topics: Muscular Dystrophy

U.S. FDA Resources

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

Primary Outcome Measures:

Safety

Secondary Outcome Measures:

mini-dystrophin gene expression at the site of gene transfer
muscle strength evaluated by Maximal Volume Isometric Contraction Testing

Estimated Enrollment:	6
Study Start Date:	March 2006
Estimated Study Completion Date:	December 2008

Detailed Description:

This phase I randomized double blind dose escalation study investigates the safety and efficacy of the mini-dystrophin gene transferred to the biceps muscle for Duchenne muscular dystrophy patients, ages 5 to 12 years of age, using a recombinant adeno-associated virus. Eligible participants must have a known dystrophin gene mutation and may be concurrently treated with corticoid steroids. The mini-dystrophin gene or a placebo agent (normal saline or empty viral capsids) are injected directly into both biceps muscles while under conscious sedation. Following the gene transfer, patients are admitted to the hospital for 48 hours of observation followed by weekly outpatient visits at the Columbus Children's Hospital Neuromuscular Clinic. A bilateral muscle biopsy is preformed following 6 weeks with long term follow up will consisting of bi-annual visits for the next 2 years.

Eligibility

Ages Eligible for Study:	5 Years to 15 Years
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Known null mutation of the Dystrophin gene
Male age of 5 years or older
If taking corticosteroids, must have dose unchanged for the past 3 months
Serum creatine kinase elevation greater than 10x normal value (established by Children's Hospital)
Progressive, symmetrical proximal muscle weakness of arms and legs

Exclusion Criteria:

Unable to cooperate for muscle strength testing
Joint contractures that prohibit muscle strength testing
Concomitant illness
Individuals predisposed to excessive vagal responses (bradyarrhythmia or hypotension)
Controlled substance abuse

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00428935

Locations

United States, Ohio
Columbus Children's Hospital
Columbus, Ohio, United States, 43205

Sponsors and Collaborators

Nationwide Children's Hospital

Asklepios Biopharmaceutical Inc.

Investigators

Principal Investigator:

Jerry R. Mendell, MD

Nationwide Children's Hospital

More Information

Additional Information:

Columbus Children's Research Institute This link exits the ClinicalTrials.gov site

Asklepios BioPharmaceutical Inc. This link exits the ClinicalTrials.gov site

Muscular Dystrophy Association This link exits the ClinicalTrials.gov site

Publications:

Watchko J, O'Day T, Wang B, Zhou L, Tang Y, Li J, Xiao X. Adeno-associated virus vector-mediated minidystrophin gene therapy improves dystrophic muscle contractile function in mdx mice. Hum Gene Ther. 2002 Aug 10;13(12):1451-60.

Wang B, Li J, Xiao X. Adeno-associated virus vector carrying human minidystrophin genes effectively ameliorates muscular dystrophy in mdx mouse model. Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13714-9.

Study ID Numbers:	CCRI IRB05-00118
Study First Received:	January 26, 2007
Last Updated:	March 18, 2007
ClinicalTrials.gov Identifier:	NCT00428935 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Nationwide Children's Hospital:

Duchenne
Muscle
Muscular Dystrophy
Gene Therapy

Dystrophin
Adeno-Associated Virus
AAV

Additional relevant MeSH terms:

Muscular Dystrophies
Muscular Diseases
Genetic Diseases, Inborn
Neuromuscular Diseases
Musculoskeletal Diseases

Muscular Disorders, Atrophic
Nervous System Diseases
Genetic Diseases, X-Linked
Muscular Dystrophy, Duchenne

ClinicalTrials.gov processed this record on November 20, 2009