A Six Month Randomized, Clinical Trial of Gentamicin in Duchenne Muscular Dystrophy Subjects With Stop Codon Mutations
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 12
- Locations
- 6
- Primary Endpoint
- 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.
Study Overview
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 Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 5 Years to 20 Years (Child, Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- No
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)
Outcomes
Primary Outcomes
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
Secondary Outcomes
- 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)
Investigators
Jerry R. Mendell
Director, Center for Gene Therapy
Nationwide Children's Hospital