Six Month Study of Gentamicin in Duchenne Muscular Dystrophy With Stop Codons - Full Text View

Sponsor:	Nationwide Children's Hospital
Collaborator:	National Institutes of Health (NIH)
Information provided by:	Nationwide Children's Hospital
ClinicalTrials.gov Identifier:	NCT00451074

Purpose

The purpose of this study is to determine the safety of giving intravenous (IV) gentamicin to boys with Duchenne muscular dystrophy who have stop codon mutations.

Condition	Intervention	Phase
Duchenne Muscular Dystrophy	Drug: Gentamicin infusions twice a week for six months	Phase I

Study Type:	Interventional
Study Design:	Treatment, Open Label, Dose Comparison, Single Group Assignment, Safety Study
Official Title:	A Six Month Randomized, Clinical Trial of Gentamicin in Duchenne Muscular Dystrophy Subjects With Stop Codon Mutations

Resource links provided by NLM:

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

MedlinePlus related topics: Muscular Dystrophy

Drug Information available for: Gentamicins

U.S. FDA Resources

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

Primary Outcome Measures:

In this phase 1 clinical trial, safety will be measured via gentamicin trough levels, audiology, and renal function tests. These lab tests will remain in the normal range while infusing gentamicin twice a week for 6 month. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Determine if gentamicin given over six months improves muscle strength. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Determine if gentamicin given over six months increases dystrophin binding at the muscle membrane. [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	12
Study Start Date:	March 2007
Estimated Study Completion Date:	June 2009
Estimated Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

Intervention Details:

Gentamicin infusions twice a week

Detailed Description:

The primary purpose of this second cohort is to see if the IV Medication, gentamicin, is safe to give twice a week for six months to boys with Duchenne muscular dystrophy (DMD). Secondarily, we want to know if gentamicin can help strengthen the muscles of boys with DMD who have a particular type of genetic mutation known as a stop codon. The gentamicin is thought to allow for "read-through" of this type of mutation which would allow for the production of dystrophin, a protein which is lacking in boys with DMD.

Eligibility

Ages Eligible for Study:	5 Years to 20 Years
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age 5-20 years
Duchenne muscular dystrophy documented by written report of stop codon mutation analysis of the dystrophin gene.
Subject is capable of cooperating for efficacy and safety testing
Absent dystrophin on muscle biopsy
Subjects may be untreated, taking prednisone or comparable corticosteroids
Subjects taking corticosteroids must be on the same dose for at least 3 months (90 days) prior to the start of the study.

Exclusion Criteria:

Known allergy to any aminoglycoside or sulfate compounds
Current use of potential nephrotoxic or ototoxic drug
Current use of corticosteroids has not been stable for 3 months (90) days
Known mutation at nucleotide 1555 in 12S rRNA gene of mitochondrial DNA (predisposes to aminoglycoside hearing loss and commercially available via Athena Diagnostics Lab). This DNA testing (Hearing susceptibility test) will be made available through funding from this grant.
Inability to hear within the range of 0 to 25 dB in any hearing frequency by pure tone audiometry
Cystatin C equal to or > 1.4mg/L
Other medical condition that would impede the conduct of study (e.g., congestive heart failure)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00451074

Locations

United States, Arizona
Neuromuscular Research Institute - Scottsdale Healthcare Hopsital at Shea
Scottsdale, Arizona, United States, 85258
United States, Kansas
University of Kansas
Kansas City, Kansas, United States, 66160-0001
United States, Ohio
The Research Institute at Nationwide Children's Hospital
Columbus, Ohio, United States, 43205-2696

Sponsors and Collaborators

Nationwide Children's Hospital

National Institutes of Health (NIH)

Investigators

Principal Investigator:

Jerry R. Mendell, M.D.

The Research Institute at Nationwide Children's Hospital/ Nationwide Children's Hospital

More Information

No publications provided

Responsible Party:	Nationwide Children's Hospital ( Jerry R. Mendell, MD )
Study ID Numbers:	NS043186, NS043186
Study First Received:	March 21, 2007
Last Updated:	April 8, 2009
ClinicalTrials.gov Identifier:	NCT00451074 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Nationwide Children's Hospital:

Stop codon mutations

Additional relevant MeSH terms:

Anti-Infective Agents
Molecular Mechanisms of Pharmacological Action
Nervous System Diseases
Enzyme Inhibitors
Pharmacologic Actions
Protein Synthesis Inhibitors
Anti-Bacterial Agents
Muscular Dystrophies
Muscular Diseases

Muscular Disorders, Atrophic
Musculoskeletal Diseases
Neuromuscular Diseases
Genetic Diseases, Inborn
Muscular Dystrophy, Duchenne
Therapeutic Uses
Gentamicins
Genetic Diseases, X-Linked

ClinicalTrials.gov processed this record on November 09, 2009