Ignite Creation Date:
2024-05-05 @ 11:21 AM
Last Modification Date:
2024-10-26 @ 9:05 AM
Study NCT ID:
NCT00005574
Status:
COMPLETED
Last Update Posted:
2008-03-04
First Post:
2000-05-02
Brief Title:
Gentamicin Treatment of Muscular Dystrophy
Sponsor:
National Institute of Neurological Disorders and Stroke NINDS
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Gentamicin Treatment of Patients With Muscular Dystrophy Due to Nonsense Mutations in Dystrophin
Status:
COMPLETED
Status Verified Date:
2000-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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
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
Detailed Description:
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 ie 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 00-N-0083 | None | None | None |