Pentoxifylline in Duchenne Muscular Dystrophy

NCT00102453 | Completed Phase 1 DMC

• 1 other identifier: CNMC0302
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 5

Brief 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. 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.

Conditions

Muscular Dystrophy, Duchenne

Keywords

Duchenne; Genetics

Outcome Measures

Primary Outcomes (1)

• 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.

  Each study visit

Secondary Outcomes (1)

• Change in manual muscle test (MMT) at 12 months

  Each study visit

Study Arms (1)

Solution

EXPERIMENTAL

All enrolled participants were give pentoxifylline in this pilot protocol.

Drug: Pentoxifylline

Interventions

Pentoxifylline DRUG

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.

Also known as: Supplier: Frank's Pharmacy, Ocala, Fl. 34474., Product: Pentoxifylline BP, CAS number: 5/6/6493, Formula weight: 278.35, Chemical formula: C13H18N4O3

Solution

Eligibility Criteria

• Age: 4 Years - 7 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Cooperative International Neuromuscular Research Group: lead

Study Sites (5)

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University at St. Louis

St Louis, Missouri, 63110, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Texas Scottish Rite Hospital

Dallas, Texas, United States

Location

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne

Interventions

Pentoxifylline

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Theobromine; Xanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Diana Escolar, MD

  Children's National Research Institute

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK

Study Record Dates

• First Submitted: January 29, 2005
• First Posted: January 31, 2005
• Study Start: March 1, 2002
• Primary Completion: July 1, 2006
• Study Completion: May 1, 2007
• Last Updated: October 27, 2011

Record last verified: 2011-10

Locations

US (5)