Six Month Study of Gentamicin in Duchenne Muscular Dystrophy With Stop Codons

Duchenne Muscular Dystrophy Clinical Trial

Official title:

A Six Month Randomized, Clinical Trial of Gentamicin in Duchenne Muscular Dystrophy Subjects With Stop Codon Mutations

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00451074
• Other study ID #: NS043186
• Secondary ID: 7R01NS043186
• Status: Completed
• Phase: Phase 1
• First received: March 21, 2007
• Last updated: March 22, 2012
• Start date: March 2007
• Est. completion date: July 2009

Study information

• Verified date: March 2012
• Source: Nationwide Children's Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: July 2009
• Est. primary completion date: July 2009
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 5 Years to 20 Years

Eligibility

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)

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Duchenne Muscular Dystrophy
• Muscular Dystrophies
• Muscular Dystrophy, Duchenne

Intervention

Drug:
• Gentamicin infusions twice a week for six months
Gentamicin infusions twice a week

Locations

Country	Name	City	State
United States	The Research Institute at Nationwide Children's Hospital	Columbus	Ohio
United States	University of Kansas	Kansas City	Kansas
United States	Neuromuscular Research Institute - Scottsdale Healthcare Hopsital at Shea	Scottsdale	Arizona

Sponsors (3)

Lead Sponsor	Collaborator
Nationwide Children's Hospital	National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

References & Publications (2)

Malik V, Rodino-Klapac LR, Viollet L, Mendell JR. Aminoglycoside-induced mutation suppression (stop codon readthrough) as a therapeutic strategy for Duchenne muscular dystrophy. Ther Adv Neurol Disord. 2010 Nov;3(6):379-89. doi: 10.1177/1756285610388693. — View Citation

Malik V, Rodino-Klapac LR, Viollet L, Wall C, King W, Al-Dahhak R, Lewis S, Shilling CJ, Kota J, Serrano-Munuera C, Hayes J, Mahan JD, Campbell KJ, Banwell B, Dasouki M, Watts V, Sivakumar K, Bien-Willner R, Flanigan KM, Sahenk Z, Barohn RJ, Walker CM, Me — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		6 months	Yes
Secondary	Determine if gentamicin given over six months improves muscle strength.		6 months	No
Secondary	Determine if gentamicin given over six months increases dystrophin binding at the muscle membrane.		6 months	No

External Links

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