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

Condition(s) targeted: Duchenne Muscular Dystrophy

Intervention: Gentamicin infusions twice a week for six months (Drug)

Phase: Phase 1

Status: Recruiting

Sponsored by: Nationwide Children's Hospital

Official(s) and/or principal investigator(s):
Jerry R. Mendell, M.D., Principal Investigator, Affiliation: The Research Institute at Nationwide Children's Hospital/ Nationwide Children's Hospital

Overall contact:
Cheryl A. Wall, RN, MS, Phone: (614) 722-2238, Email: Cheryl.Wall@nationwidechildrens.org

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.

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

Study design: Treatment, Open Label, Dose Comparison, Single Group Assignment, Safety Study

Primary outcome: Safety

Secondary outcome:

Determine if gentamicin given over six months improves muscle strength.

Determine if gentamicin given over six months increases dystrophin binding at the muscle membrane.

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.

Minimum age: 5 Years. Maximum age: 20 Years. Gender(s): Male.

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)

Cheryl A. Wall, RN, MS, Phone: (614) 722-2238, Email: Cheryl.Wall@nationwidechildrens.org

Neuromuscular Research Institute - Scottsdale Healthcare Hopsital at Shea, Scottsdale, Arizona 85258, United States; Recruiting
Richardo D Bien-Willner, BS, Phone: 480-314-1007, Ext: 1026, Email: rwillner@azneuromuscular.org
Kumaraswamy Sivakumar, MD, MRCP, Principal Investigator

University of Kansas, Kansas City, Kansas 66160-0001, United States; Recruiting
Victoria Watts, BSN, RN, Phone: 913-588-5479, Email: vwatts@kumc.edu
Richard J Barohn, MD, FAAN, Principal Investigator

The Research Institute at Nationwide Children's Hospital/ Nationwide Children's, Columbus, Ohio 43205, United States; Recruiting
Cheryl A. Wall, RN, MS, Phone: 614-722-2238, Email: Cheryl.Wall@nationwidechildrens.org
Susan A. Gailey, BA, Phone: 614-355-2897, Email: Susan.Gailey@nationwidechildrens.org

Starting date: March 2007
Ending date: June 2009
Last updated: July 16, 2008