Pentoxifylline in Duchenne Muscular Dystrophy - Full Text View

Sponsored by:	Cooperative International Neuromuscular Research Group
Information provided by:	Cooperative International Neuromuscular Research Group
ClinicalTrials.gov Identifier:	NCT00102453

Purpose

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.

Condition	Intervention	Phase
Muscular Dystrophy, Duchenne	Drug: Pentoxifylline	Phase I Phase II

Genetics Home Reference related topics: Duchenne and Becker muscular dystrophy L1 syndrome

MedlinePlus related topics: Muscular Dystrophy

Drug Information available for: Pentoxifylline Pentoxyl

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:	An Open-Label Pilot Study of Pentoxifylline in Steroid-Naive Duchenne Muscular Dystrophy

Further study details as provided by Cooperative International Neuromuscular Research Group:

Primary Outcome Measures:

QMT measurements

Secondary Outcome Measures:

Change in manual muscle test (MMT) at 12 months

Estimated Enrollment:	15
Study Start Date:	March 2002
Estimated Study Completion Date:	July 2006

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.

Eligibility

Ages Eligible for Study:	4 Years to 7 Years
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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',
- 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.

Exclusion Criteria:

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).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00102453

Locations

United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States
United States, Missouri
Washington University at St. Louis
St. Louis, Missouri, United States
United States, Pennsylvania
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States
United States, Texas
Texas Scottish Rite Hospital
Dallas, Texas, United States

Sponsors and Collaborators

Cooperative International Neuromuscular Research Group

Investigators

Study Chair:

Diana Escolar, MD

Childrens Research Institute

More Information

Study ID Numbers:	CNMC0302
Study First Received:	January 29, 2005
Last Updated:	June 9, 2008
ClinicalTrials.gov Identifier:	NCT00102453
Health Authority:	United States: Institutional Review Board

Keywords provided by Cooperative International Neuromuscular Research Group:

Duchenne
Genetics

Study placed in the following topic categories:

Muscular dystrophy, Duchenne and Becker type
Pentoxifylline
Muscular Dystrophies
Muscular Diseases
Becker's muscular dystrophy
Muscular Disorders, Atrophic
Musculoskeletal Diseases

Neuromuscular Diseases
Genetic Diseases, Inborn
Muscular Dystrophy, Duchenne
Genetic Diseases, X-Linked
Duchenne muscular dystrophy
Atrophy
Muscular dystrophy

Additional relevant MeSH terms:

Radiation-Protective Agents
Vasodilator Agents
Antioxidants
Molecular Mechanisms of Pharmacological Action
Nervous System Diseases
Hematologic Agents
Physiological Effects of Drugs
Enzyme Inhibitors

Cardiovascular Agents
Protective Agents
Pharmacologic Actions
Phosphodiesterase Inhibitors
Therapeutic Uses
Free Radical Scavengers
Platelet Aggregation Inhibitors

ClinicalTrials.gov processed this record on January 15, 2009