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Pentoxifylline in Duchenne Muscular Dystrophy

Primary Purpose

Muscular Dystrophy, Duchenne

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Pentoxifylline
Sponsored by
Cooperative International Neuromuscular Research Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Muscular Dystrophy, Duchenne focused on measuring Duchenne, Genetics

Eligibility Criteria

4 Years - 7 Years (Child)MaleDoes not accept healthy volunteers

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).

Sites / Locations

  • Children's National Medical Center
  • Mayo Clinic
  • Washington University at St. Louis
  • Children's Hospital of Pittsburgh
  • Texas Scottish Rite Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Solution

Arm Description

All enrolled participants were give pentoxifylline in this pilot protocol.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

First Posted
January 29, 2005
Last Updated
October 26, 2011
Sponsor
Cooperative International Neuromuscular Research Group
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1. Study Identification

Unique Protocol Identification Number
NCT00102453
Brief Title
Pentoxifylline in Duchenne Muscular Dystrophy
Official Title
An Open-Label Pilot Study of Pentoxifylline in Steroid-naive Duchenne Muscular Dystrophy
Study Type
Interventional

2. Study Status

Record Verification Date
October 2011
Overall Recruitment Status
Completed
Study Start Date
March 2002 (undefined)
Primary Completion Date
July 2006 (Actual)
Study Completion Date
May 2007 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Cooperative International Neuromuscular Research Group

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Muscular Dystrophy, Duchenne
Keywords
Duchenne, Genetics

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
17 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Solution
Arm Type
Experimental
Arm Description
All enrolled participants were give pentoxifylline in this pilot protocol.
Intervention Type
Drug
Intervention Name(s)
Pentoxifylline
Other Intervention Name(s)
Supplier: Frank's Pharmacy, Ocala, Fl. 34474., Product: Pentoxifylline BP, CAS number: 5/6/6493, Formula weight: 278.35, Chemical formula: C13H18N4O3
Intervention Description
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.
Primary Outcome Measure Information:
Title
QMT measurements
Description
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.
Time Frame
Each study visit
Secondary Outcome Measure Information:
Title
Change in manual muscle test (MMT) at 12 months
Description
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.
Time Frame
Each study visit

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
4 Years
Maximum Age & Unit of Time
7 Years
Accepts Healthy Volunteers
No
Eligibility 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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Diana Escolar, MD
Organizational Affiliation
Children's National Research Institute
Official's Role
Study Chair
Facility Information:
Facility Name
Children's National Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Washington University at St. Louis
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Children's Hospital of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Texas Scottish Rite Hospital
City
Dallas
State/Province
Texas
Country
United States

12. IPD Sharing Statement

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Pentoxifylline in Duchenne Muscular Dystrophy

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