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

Phase 1

Completed

• Conditions: Duchenne Muscular Dystrophy

• Registration Number: NCT00451074
• Lead Sponsor: Nationwide Children's Hospital

Brief 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.

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.

Study Timeline

• Study Start: 2007-03
• Study First Submitted: 2007-03-21
• Study First Submitted QC: 2007-03-21
• Study First Posted: 2007-03-23
• Primary Completion: 2009-07
• Study Completion: 2009-07
• Status Verified: 2012-03
• Last Update Submitted: 2012-03-22
• Last Update Posted: 2012-03-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 12

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

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
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

Secondary Outcome Measures

Name	Time	Method
Determine if gentamicin given over six months improves muscle strength.	6 months
Determine if gentamicin given over six months increases dystrophin binding at the muscle membrane.	6 months

Trial Locations

Locations (3)

University of Kansas; 🇺🇸 Kansas City, Kansas, United States

The Research Institute at Nationwide Children's Hospital; 🇺🇸 Columbus, Ohio, United States

Neuromuscular Research Institute - Scottsdale Healthcare Hopsital at Shea; 🇺🇸 Scottsdale, Arizona, United States