Duchenne Muscular Dystrophy
Conditions
Keywords
Stop codon mutations
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.
Interventions
DRUGGentamicin infusions twice a week for six months
Gentamicin infusions twice a week
Sponsors
National Institutes of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Nationwide Children's Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
5 Years to 20 Years
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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 |
Countries
United States
Outcome results
None listed