Becker Muscular DystrophyPhase 1NCT00005574
Gentamicin Treatment of Muscular Dystrophy
A Phase 1 study testing Gentamicin in people with Becker Muscular Dystrophy and Duchenne Muscular Dystrophy, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Becker Muscular Dystrophy, Duchenne Muscular Dystrophy
- What is being tested?
- Gentamicin
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2000to Jan 2001
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Neurological Disorders and Stroke (NINDS)
Bethesda, Maryland, 20892
About this study
Official title: Gentamicin Treatment of Patients With Muscular Dystrophy Due to Nonsense Mutations in Dystrophin
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.)
Read more
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.
Read the 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, 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.
- Being tested
- Gentamicin
- Keywords
- Becker Muscular Dystrophy, Duchenne Muscular Dystrophy, Muscle Disease, Myopathy
- Medical subject headings
- Muscular Dystrophy, Duchenne, Muscular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GentamicinDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2002 (estimated)
- Study startFeb 2000
- Study completionJan 2001
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Becker Muscular DystrophyStudies of the same condition, open and under way.
- More trials run by National Institute of Neurological Disorders and Stroke (NINDS)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Enrolment
- 4 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00005574
- Sponsor's protocol ID
- 000083
- Other IDs
- 00-N-0083
- Status last verified
- Jan 2000
- First submitted
- 2 May 2000
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
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.
PubMed 9694103Bedwell 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.
PubMed 9359706Hoffman 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.
PubMed 3319190
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Gentamicin Treatment of Patients With Muscular Dystrophy Due to Nonsense Mutations in Dystrophin
- ClinicalTrials.gov ID
- NCT00005574
- Acronym / sponsor ID
- 000083
- Keywords
- Becker Muscular Dystrophy, Duchenne Muscular Dystrophy, Muscle Disease, Myopathy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 4 participants
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- Feb 2000
- Study completion
- Jan 2001
- First posted
- 10 Dec 2002 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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, 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.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Gentamicin | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2008.
- Background: PubMed 9694103Bass 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.
- Background: PubMed 9359706Bedwell 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.
- Background: PubMed 3319190Hoffman 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Gentamicin in people with Becker Muscular Dystrophy and Duchenne Muscular Dystrophy, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00005574, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2008.