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

March 22, 2012 updated by: Jerry R. Mendell, Nationwide Children's Hospital

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

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.

Study Overview

Status

Completed

Conditions

Duchenne Muscular Dystrophy

Intervention / Treatment

Drug: Gentamicin infusions twice a week for six months

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 Type

Interventional

Enrollment (Actual)

Phase

Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

United States
- Arizona
  - Scottsdale, Arizona, United States, 85258
    - Neuromuscular Research Institute - Scottsdale Healthcare Hopsital at Shea
- Kansas
  - Kansas City, Kansas, United States, 66160-0001
    - University of Kansas
- Ohio
  - Columbus, Ohio, United States, 43205-2696
    - The Research Institute at Nationwide Children's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

5 years to 20 years (Child, Adult)

Accepts Healthy Volunteers

Genders Eligible for Study

Male

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Treatment
Allocation: N/A
Interventional Model: Single Group Assignment
Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome 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. Time Frame: 6 months	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Determine if gentamicin given over six months improves muscle strength. Time Frame: 6 months	6 months
Determine if gentamicin given over six months increases dystrophin binding at the muscle membrane. Time Frame: 6 months	6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Nationwide Children's Hospital

Collaborators

National Institute of Neurological Disorders and Stroke (NINDS)

National Institutes of Health (NIH)

Investigators

Principal Investigator: Jerry R. Mendell, M.D., The Research Institute at Nationwide Children's Hospital/ Nationwide Children's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2007

Primary Completion (Actual)

July 1, 2009

Study Completion (Actual)