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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Duchenne Muscular Dystrophy

Intervention / Treatment
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* Drug: Gentamicin infusions twice a week for six months


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 20 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Gentamicin infusions twice a week for six months|Gentamicin infusions twice a week|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stop codon mutations