Gentamicin Treatment of Muscular Dystrophy

NCT00005574 | Completed Phase 1

• 2 other identifiers: 00008300-N-0083
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Becker Muscular Dystrophy; Duchenne Muscular Dystrophy

Keywords

Becker Muscular Dystrophy; Duchenne Muscular Dystrophy; Muscle Disease; Myopathy

Interventions

Gentamicin DRUG

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

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.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead

Study Sites (1)

National Institute of Neurological Disorders and Stroke (NINDS)

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Bass KD, Larkin SE, Paap C, Haase GM. Pharmacokinetics of once-daily gentamicin dosing in pediatric patients. J Pediatr Surg. 1998 Jul;33(7):1104-7. doi: 10.1016/s0022-3468(98)90540-1.

  PMID: 9694103 BACKGROUND

• Bedwell DM, Kaenjak A, Benos DJ, Bebok Z, Bubien JK, Hong J, Tousson A, Clancy JP, Sorscher EJ. Suppression of a CFTR premature stop mutation in a bronchial epithelial cell line. Nat Med. 1997 Nov;3(11):1280-4. doi: 10.1038/nm1197-1280.

  PMID: 9359706 BACKGROUND

• Hoffman EP, Brown RH Jr, Kunkel LM. Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell. 1987 Dec 24;51(6):919-28. doi: 10.1016/0092-8674(87)90579-4.

  PMID: 3319190 BACKGROUND

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne; Muscular Diseases

Interventions

Gentamicins

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Aminoglycosides; Glycosides; Carbohydrates

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: May 2, 2000
• First Posted: December 10, 2002
• Study Start: February 1, 2000
• Study Completion: January 1, 2001
• Last Updated: March 4, 2008

Record last verified: 2000-01

Locations

US (1)