Muscular Dystrophy, DuchennePhase 1/2NCT00102453
Pentoxifylline in Duchenne Muscular Dystrophy
A Phase 1/2 study testing Pentoxifylline in people with Muscular Dystrophy, Duchenne, run by Cooperative International Neuromuscular Research Group at 5 sites in United States.
Trial summary
In this study, the primary aim will be to estimate the magnitude and variability of strength change over time that may be expected for subjects on the study treatment. This estimate of effect will allow us to develop a rigorous statistical plan in the future randomized study. Read more about this study
- Who is it for?
- Ages 4 to 7 years, men only
- Conditions the study is for
- Muscular Dystrophy, Duchenne
- What is being tested?
- Pentoxifylline
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 5 sitesUnited States
- Study dates
- Mar 2002to May 2007
- Phase
- Phase 1/2
- 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 4 to 7 years
- Men only
- No healthy volunteers
- Child
Who may be able to join
- Male
- Age 4 to 7 years
- Ambulant independently. Subjects may use a wheelchair occasionally, but only for long distances
- Diagnosis of DMD confirmed by at least one of the following:
- Dystrophin immunofluorescence and/or immunoblot showing complete dystrophin deficiency, and clinical picture consistent with typical DMD OR
- Gene deletion test positive (missing one or more exons) in the central rod domain (exons 25-60) of dystrophin, where reading frame can be predicted as 'out-of-frame',
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- and clinical picture consistent with typical DMD.
- Complete dystrophin gene sequencing showing an alteration (point mutation, duplication, or other mutation resulting in a stop codon mutation) that can be definitely associated with DMD, with a typical clinical picture of DMD.
- Positive family history of DMD confirmed by one of the criteria listed above in a sibling or maternal uncle, and clinical picture typical of DMD.
- Glucocorticosteroid - naïve (i.e. has not been treated with prednisone or Deflazacort within 1 year before onset of the study)
- Has not participated in other therapeutic research protocol within the last 6 months.
- Evidence of muscle weakness by MRC score or clinical functional evaluation
- Ability to provide reproducible repeat QMT bicep score of either the right or left arm within 15% of first assessment score.
Who cannot join
- Symptomatic DMD carrier
- Use of any medication, nutritional supplement or herb for treatment of DMD within the last 3 months.
- Symptomatic cardiomyopathy or ventricular arrhythmias
- History of significant concomitant illness, impairment of blood clotting ability (as evidenced by increased PT/PTT or bleeding time over the upper limit of normal (ULN)), recent cerebral or retinal hemorrhage, bleeding diathesis, gastric ulcer, hypotension or significant impairment of renal or hepatic function (defined as serum creatinine and GGT respectively, greater than 1.5 times normal upper limit for age and gender).
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Texas Scottish Rite Hospital
Dallas, Texas
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15213
Mayo Clinic
Rochester, Minnesota, 55905
Washington University at St. Louis
St Louis, Missouri, 63110
Children's National Medical Center
Washington D.C., District of Columbia, 20010
About this study
Official title: An Open-Label Pilot Study of Pentoxifylline in Steroid-naive Duchenne Muscular Dystrophy
In this study, the primary aim will be to estimate the magnitude and variability of strength change over time that may be expected for subjects on the study treatment. This estimate of effect will allow us to develop a rigorous statistical plan in the future randomized study. The specific estimation technique to be applied will use a linear random effects model to estimate average strength change during the 3-month lead-in period and then during the twelve-month treatment period, taking into account the quantitative muscle testing (QMT) measures for each subject. Accounting for the correlation between repeated measures from each subject by using a random effects model will yield an unbiased estimate of variability for the population average change in strength. We will use an analysis of pre- and post-treatment data to inform a best estimate of treatment effect. For example, the difference in QMT trends pre- and post-treatment would provide a straightforward measure of efficacy.
Read the detailed description
Duchenne muscular dystrophy (DMD) is a progressive disease of skeletal muscle caused by the absence of dystrophin due to a genetic mutation in the x-linked dystrophin gene. The absence of dystrophin results in a fragile muscle membrane that permits an abnormal permeability to electrolytes, especially Ca ++. The increase in intracellular calcium triggers a pathological cascade of events that ultimately results in muscle necrosis and fibrosis, which impedes normal muscle regeneration. The increased knowledge of the pathophysiology of DMD opens the opportunity for pharmacological treatment, with the purpose of altering the disease process and or reverting the muscle degeneration.
This research study requires having Duchenne muscular dystrophy (DMD) and the subject to be between 4 and 7 years old. We expect 5 children to take part in this study at Children's Hospital and 10 other children to participate at other hospitals worldwide.
There will be two (2) screening visits to help decide whether you will be able to participate in the study. At the second screening visit, there will be a blood test (about 13 tablespoons of blood), and an EKG. Once the study doctors decide eligibility to be in the study, the subject will then come back once a month for three months to have his strength tested. After three months, the subject will begin to take the pentoxifylline and have an MRI (you will have a test called an MRI to look inside the muscles of your legs). This will continue for 12 months.
- Conditions
- Muscular Dystrophy, Duchenne
- Being tested
- Pentoxifylline
- Keywords
- Duchenne, Genetics
- Medical subject headings
- Muscular Dystrophy, Duchenne
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PentoxifyllineDrug
Also called Supplier: Frank's Pharmacy, Ocala, Fl. 34474., Product: Pentoxifylline BP, CAS number: 5/6/6493, Formula weight: 278.35
Pentoxifylline dosing: 20mg/Kg/day in a 20 mg/mL solution. Maximum dose of 1200mg/day. Dosing split into two equal parts taken morning and night with food.
| Study group | Role | What they receive |
|---|---|---|
| Solution | Experimental | All enrolled participants were give pentoxifylline in this pilot protocol. Receives: Drug: Pentoxifylline |
What is being measured
The primary outcome is the main question the study is designed to answer.
QMT measurements
Quantitative muscle testing (QMT) is a technique utilized to assess muscle strength. Measurements of force are collected using a load cell while performing a maximum voluntary isometric contraction. This set-up is able to measure changes in strength of 0.25 lb which provides accurate and sensitive measurement of muscular strength. QMT is performed by a CINRG physical therapist.
Measured: Each study visit
Secondary outcomes (1)
Change in manual muscle test (MMT) at 12 months
Manual muscle testing (MMT), which is graded according to the modified Medical Research Council (MRC) scale, is a test of a participant's muscle strength, or ability of the muscle to move a part of the body against resistance. A CINRG physical therapist will perform MMT testing with each participant.
Measured: Each study visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2005 (estimated)
- Study startMar 2002
- Primary completionJul 2006
- Study completionMay 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Muscular Dystrophy, DuchenneStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cooperative International Neuromuscular Research Group
- Sponsor type
- Research network
- Investigators
- Diana Escolar, MD, Study chair, Children's National Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00102453
- Sponsor's protocol ID
- CNMC0302
- Status last verified
- Oct 2011
- First submitted
- 29 Jan 2005
- Last updated
- 27 Oct 2011
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Pilot Study of Pentoxifylline in Steroid-naive Duchenne Muscular Dystrophy
- ClinicalTrials.gov ID
- NCT00102453
- Acronym / sponsor ID
- CNMC0302
- Conditions
- Muscular Dystrophy, Duchenne
- Keywords
- Duchenne, Genetics
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Cooperative International Neuromuscular Research GroupResearch network
- Study start
- Mar 2002
- Primary completion
- Jul 2006 (actual)
- Study completion
- May 2007 (actual)
- First posted
- 31 Jan 2005 (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.
In this study, the primary aim will be to estimate the magnitude and variability of strength change over time that may be expected for subjects on the study treatment. This estimate of effect will allow us to develop a rigorous statistical plan in the future randomized study. The specific estimation technique to be applied will use a linear random effects model to estimate average strength change during the 3-month lead-in period and then during the twelve-month treatment period, taking into account the quantitative muscle testing (QMT) measures for each subject. Accounting for the correlation between repeated measures from each subject by using a random effects model will yield an unbiased estimate of variability for the population average change in strength. We will use an analysis of pre- and post-treatment data to inform a best estimate of treatment effect. For example, the difference in QMT trends pre- and post-treatment would provide a straightforward measure of efficacy.
Detailed description
Duchenne muscular dystrophy (DMD) is a progressive disease of skeletal muscle caused by the absence of dystrophin due to a genetic mutation in the x-linked dystrophin gene. The absence of dystrophin results in a fragile muscle membrane that permits an abnormal permeability to electrolytes, especially Ca ++. The increase in intracellular calcium triggers a pathological cascade of events that ultimately results in muscle necrosis and fibrosis, which impedes normal muscle regeneration. The increased knowledge of the pathophysiology of DMD opens the opportunity for pharmacological treatment, with the purpose of altering the disease process and or reverting the muscle degeneration.
This research study requires having Duchenne muscular dystrophy (DMD) and the subject to be between 4 and 7 years old. We expect 5 children to take part in this study at Children's Hospital and 10 other children to participate at other hospitals worldwide.
There will be two (2) screening visits to help decide whether you will be able to participate in the study. At the second screening visit, there will be a blood test (about 13 tablespoons of blood), and an EKG. Once the study doctors decide eligibility to be in the study, the subject will then come back once a month for three months to have his strength tested. After three months, the subject will begin to take the pentoxifylline and have an MRI (you will have a test called an MRI to look inside the muscles of your legs). This will continue for 12 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Solution | Experimental | Drug: PentoxifyllineAll enrolled participants were give pentoxifylline in this pilot protocol. |
Who may qualify
- Ages
- 4 to 7 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (13 listed)
- Male
- Age 4 to 7 years
- Ambulant independently. Subjects may use a wheelchair occasionally, but only for long distances
- Diagnosis of DMD confirmed by at least one of the following:
- Positive family history of DMD confirmed by one of the criteria listed above in a sibling or maternal uncle, and clinical picture typical of DMD.
Key exclusion criteria (4 listed)
- Symptomatic DMD carrier
- Use of any medication, nutritional supplement or herb for treatment of DMD within the last 3 months.
- Symptomatic cardiomyopathy or ventricular arrhythmias
- History of significant concomitant illness, impairment of blood clotting ability (as evidenced by increased PT/PTT or bleeding time over the upper limit of normal (ULN)), recent cerebral or retinal hemorrhage, bleeding diathesis, gastric ulcer, hypotension or significant impairment of renal or hepatic function (defined as serum creatinine and GGT respectively, greater than 1.5 times normal upper limit for age and gender).
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 |
|---|---|---|
| PentoxifyllineAlso: Supplier: Frank's Pharmacy, Ocala, Fl. 34474., Product: Pentoxifylline BP, CAS number: 5/6/6493, Formula weight: 278.35Pentoxifylline dosing: 20mg/Kg/day in a 20 mg/mL solution. Maximum dose of 1200mg/day. Dosing split into two equal parts taken morning and night with food. | Drug | Solution |
Primary outcome
QMT measurements
Time frame: Each study visit
Quantitative muscle testing (QMT) is a technique utilized to assess muscle strength. Measurements of force are collected using a load cell while performing a maximum voluntary isometric contraction. This set-up is able to measure changes in strength of 0.25 lb which provides accurate and sensitive measurement of muscular strength. QMT is performed by a CINRG physical therapist.
1 secondary outcome
Change in manual muscle test (MMT) at 12 months
Time frame: Each study visit
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 27 Oct 2011.
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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.
Diana Escolar, MD study chair
Children's National Research Institute
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Pentoxifylline in people with Muscular Dystrophy, Duchenne, run by Cooperative International Neuromuscular Research Group at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Oct 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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.
What does the primary outcome measure?
QMT measurements (time frame: Each study visit). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Oct 2011.