Gentamicin Treatment of Muscular Dystrophy

This study will evaluate the antibiotic gentamicin for treating patients with muscular dystrophy caused by a specific genetic abnormality known as a nonsense mutation. In studies of mice with this type of muscular dystrophy, gentamicin treatment produced positive changes in muscle tissue.

Patients with Duchenne or Becker muscular dystrophy caused by nonsense mutations by may be eligible for this 2-week study. Before starting treatment, patients will have evaluations of muscle strength and general well being. Two muscle tissue samples will be taken by needle biopsy, under local anesthetic and sedation. Because of potential risks of hearing loss and kidney toxicity associated with gentamicin, patients will also have a hearing test and blood and urine tests for kidney function before starting treatment. (Currently, gentamicin is commonly prescribed for serious infections of the lungs, heart, and digestive and urinary tracts; adverse effects of hearing loss and kidney toxicity can occur with excessively high drug doses.)

Patients will be hospitalized during drug treatment. Gentamicin will be given intravenously (through a vein) once a day for 14 days. Blood samples will be collected daily to monitor drug levels and determine dosage adjustments, if necessary. Urine samples will be collected to assess kidney function. Hearing tests will be done on days 7 and 10.

On the last day of the study, hearing, kidney function, and muscle strength will be tested and the results compared with pre-treatment levels. Blood and muscle samples will also be taken again for pre-treatment comparison. Hearing, blood, urine, and muscle strength tests will be repeated one month after treatment ends for comparison with previous results.

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Key information

Conditions

Becker Muscular Dystrophy Congenital, Hereditary, and Neonatal Diseases and Abnormalities Duchenne Muscular Dystrophy Genetic Diseases, Inborn Genetic Diseases, X-Linked Muscular Diseases Muscular Disorders, Atrophic Muscular Dystrophies Muscular Dystrophy, Duchenne Musculoskeletal Diseases Nervous System Diseases Neuromuscular Diseases

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

National Institute of Neurological Disorders and Stroke (NINDS)

Bethesda, Maryland, 20892, United States

About this study

Duchenne muscular dystrophy (DMD) is a fatal disease of progressive muscular weakness for which there is currently no effective treatment. The disease is caused by mutations in the gene for dystrophin. A subset of these mutations includes nonsense mutations, i.e., premature stop codons. Previous studies have shown that aminoglycosides are effective in allowing translation through stop codons. Recently, gentamicin was shown to restore functional dystrophin in a mouse model of DMD. The objective of this protocol is to determine if gentamicin is also an effective treatment in patients with DMD caused by nonsense mutations. This will be a preliminary, non-blinded study in which levels of intravenous gentamicin previously established to be safe, will be administered to identified patients meeting inclusion criteria over a two-week period. These patients will have CLIA approved laboratory documented stop codon mutations in the dystrophin gene. Quantitative dystrophin expression will be the primary outcome. Strength measurements will also be assessed before and immediately after the two-week treatment period. Follow-up evaluations will be made at one month. For this subset of patients with DMD it is anticipated that there will be a transient increase in dystrophin expression with a possible corresponding transient improvement in strength. Subsequent blinded studies to evaluate the most effective dose and dosing intervals would then be pursued.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Diagnosis of DMD or Becker muscular dystrophy with confirmed dystrophin nonsense mutation.

Measurable limb or pulmonary weakness.

Signed consent.

Must not have a history of hypersensitivity reaction to an aminoglycoside.

Must not have abnormal baseline hearing.

Must not have abnormal baseline kidney function or serum creatinine level.

Must not be currently enrolled in another clinical trial.

Must not have recent (within past 3 months) initiation of prednisone or creatinine therapy.

Must not have a history of significant concomitant illness.

Must not have concomitant use of aminoglycoside or other nephrotoxic agent.

Treatment and study plan

Gentamicin

Drug

Sponsors and collaborators

Lead sponsor

National Institute of Neurological Disorders and Stroke (NINDS)

Nih

Registry information

Official study title

Gentamicin Treatment of Patients With Muscular Dystrophy Due to Nonsense Mutations in Dystrophin

Important dates

Study start: 2000
Study completion: 2001
First posted: Dec 10, 2002
Registry last updated: Mar 4, 2008

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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Completed