Clinical trial NCT00451074: Six Month Study of Gentamicin in Duchenne Muscular Dystrophy With Stop Codons
Official title: A Six Month Randomized, Clinical Trial of Gentamicin in Duchenne Muscular Dystrophy Subjects With Stop Codon Mutations
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Duchenne Muscular Dystrophy
Keywords: Stop codon mutations
Lead sponsor: Nationwide Children's Hospital
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2007-03-23
Enrollment: 12
Sex: MALE
Minimum age (years): 5
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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)

Primary outcomes:
measure: 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.
timeFrame: 6 months
Secondary outcomes:
measure: Determine if gentamicin given over six months improves muscle strength.
timeFrame: 6 months
measure: Determine if gentamicin given over six months increases dystrophin binding at the muscle membrane.
timeFrame: 6 months
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Neuromuscular Research Institute - Scottsdale Healthcare Hopsital at Shea
state: Arizona
city: Kansas City
country: United States
facility: University of Kansas
state: Kansas
city: Columbus
country: United States
facility: The Research Institute at Nationwide Children's Hospital
state: Ohio
Study officials:
affiliation: The Research Institute at Nationwide Children's Hospital/ Nationwide Children's Hospital
name: Jerry R. Mendell, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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, Mendell JR. Gentamicin-induced readthrough of stop codons in Duchenne muscular dystrophy. Ann Neurol. 2010 Jun;67(6):771-80. doi: 10.1002/ana.22024.