Study of Daily Pentoxifylline as a Rescue Treatment in Duchenne Muscular Dystrophy

A Double-Blinded Randomized Placebo Controlled Study of Daily Pentoxifylline as a Rescue Treatment in DMD

The purpose of this study is to see if male children with Duchenne muscular dystrophy (DMD) have changes in strength when given the drug Pentoxifylline as a rescue treatment. A total of 64 subjects are expected to participate through all other centers of the Cooperative International Neuromuscular Research Group (CINRG) worldwide.

The primary purpose of this study is to see whether the addition of pentoxifylline to a steroid regimen is effective in treating deteriorating muscle strength by comparing the muscle strength of PTX treated subjects and placebo treated subjects.

Study Overview

• Status: Completed
• Conditions: Muscular Dystrophy, Duchenne
• Intervention / Treatment: Drug: Pentoxifylline

Detailed Description

DMD is the most common and devastating type of muscular dystrophy (incidence 1 in 3500 live born males worldwide). DMD is characterized by a complete loss of dystrophin, leading to progressive muscle weakness and wasting.

No cure is currently available despite our present understanding of the disorder and the discovery and characterization of the causative gene and its protein product dystrophin in 1987. Corticosteroids (prednisone, deflazacort) may delay disease progression and until now it is the only treatment that proved to be beneficial for patients with DMD. Other alternative supplements like creatine and glutamine also delay diseased progression.

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1434
    • Hospital Frances
• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3052
      • Children's Hospital
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2T 5C7
      • Alberta Children's Hospital
    • Edmonton, Alberta, Canada, T6G 2J3
      • University of Alberta
• Israel
  • Jerusalem, Israel, 91240
    • Hadassah Hospital, Mt. Scopus
• Italy
  • Pavia, Italy, 27100
    • IRCCS C Mondino Foundation
• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Medical Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Washington University, St. Louis
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Children's Hospital of Pittsburgh
  • Tennessee
    • Memphis, Tennessee, United States, 38104
      • University of Tennessee

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Male
• Age 7 years to 100 years
• Ability to ambulate for 10 meters. Assistive devices are allowed.
• Diagnosis of DMD confirmed by at least one the following:
• On stable dose of prednisone, prednisolone or deflazacort for at least 12 months prior to screening.
• Participants who are on stable dose of any combination of the following compounds (creatine, glutamine, coenzyme Q10, vitamin E, C or D, JUVEN, arginine, calcium) must have taken these medications for at least 2 months prior to screening. Subjects are not required to take these medications to participate in the study.
• All other herbs, supplements or green tea (other than those noted above) have been discontinued 3 months prior to screening.
• Ability to provide reproducible QMT bicep score with no more than 15% variation between scores during screening.
• Normal blood clotting ability evidenced by a platelet function assessment (PFA).

Exclusion Criteria:

• Currently enrolled in another treatment clinical trial.
• History of significant concomitant illness or significant impairment of renal or hepatic function.
• History of impairment of blood clotting ability (as evidenced by increased PT/PTT or PFA over the upper limit of normal (ULN)).
• Recent cerebral or retinal hemorrhage.
• History of bleeding diathesis or gastric ulcer.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: 1; Pentoxifylline	Drug: Pentoxifylline; Participants will be randomized to receive either pentoxifylline or placebo in addition to their stable steroid therapy. Active drug and placebo preparations will be supplied as gel capsules of identical size, appearance and taste. Active drug capsules will contain one 400 mg time-release pentoxifylline tablet and inert filler. Placebo capsules will contain inert filler. Based on weight at screening, <30 mg will receive 1 400 capsule/day; 30-49 kg will receive two 400 capsules/day; 50 kg or greater will receive three 400 mg capsules/day.; Other Names: Trental
NO_INTERVENTION: 2; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Quantitative muscle strength will be measured using a CINRG Quantitative Muscle System (CQMS). The highest value of two consecutive maximal efforts will be recorded. The primary strength endpoint will be total CQMS score.	January 2008

Secondary Outcome Measures

Outcome Measure	Time Frame
Strength of arm, leg and grip QMT scores Measured Screening and Months 1, 3, 6, 9 & 12	January 2008
Manual Muscle Testing (MMT) score measured at screening and months 1, 3, 6, 9 & 12 using the Medical Research Council (MRC) scoring system.	January 2008
Functional evaluations measured at screening and months 1, 3, 6, 9 & 12	January 2008
Time function assessments, including time rising from the floor, time to climb four standard stairs, and time to walk 10 meters. They will be measured at screening and months 1, 3, 6, 9 & 12.	January 2008
pulmonary function test (PFA's) measured at screening and months 1, 3, 6, 9 & 12	January 2008
Pediatric Quality of Life (PQOL) measured at screening and months 1, 3, 6, 9 & 12	January 2008
Goniometry measured at screening and months 1, 3, 6, 9 & 12	January 2008
TNF-alpha and TGF-beta measured at screening and months 1, 3, 6, 9 & 12	February 2008

Collaborators and Investigators

• Sponsor: Cooperative International Neuromuscular Research Group
• Investigators: Study Chair: Diana Escolar, MD, Children's National Medical Center, Center for Genetic Medicine

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: September 1, 2005
• Primary Completion (ACTUAL): December 1, 2007
• Study Completion (ACTUAL): January 1, 2008

Study Registration Dates

• First Submitted: October 21, 2005
• First Submitted That Met QC Criteria: October 21, 2005
• First Posted (ESTIMATE): October 25, 2005

Study Record Updates

• Last Update Posted (ESTIMATE): October 27, 2011
• Last Update Submitted That Met QC Criteria: October 26, 2011
• Last Verified: October 1, 2011

More Information

Terms related to this study

• Keywords: Genetic; DMD; Duchenne; Muscular Dystrophy
• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophy, Duchenne; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Protective Agents; Antioxidants; Phosphodiesterase Inhibitors; Free Radical Scavengers; Radiation-Protective Agents; Pentoxifylline
• Other Study ID Numbers: CNMC0705