CLINICAL TRIAL/STUDY

DISEASE CLASSIFICATION(S): Duchenne muscular dystrophy (DMD)

NAME OF CLINICAL TRIAL/STUDY:

A randomized study of daily vs. high dose weekly Prednisone therapy in Duchenne muscular dystrophy

PURPOSE AND RATIONALE:

This trial is to test the effectiveness of a high-dose, weekend-only regimen of prednisone in Duchenne muscular dystrophy (DMD) as compared to the standard, moderate-dose, daily regimen that is commonly used in this disease. The primary aim of this study will be to measure the ability of prednisone to increase muscle strength in boys in both treatment groups. This is a measure of effectiveness (efficacy). In addition, the investigators will compare side effect rates between the two groups, since they believe that side effects of the new regimen will likely be less severe. This is a measure of safety.

Boys who are enrolled in this study should not have been exposed to steroid. There will be two screening visits to ensure a reproducible manual muscle test and confirmation of inclusion / exclusion criteria.  The subjects will then be randomized and put into either the daily or weekly regimen. This will be a 12 month prospective study with follow-up visits at month one, three and then every three months.

STUDY DETAILS:

Duchenne muscular dystrophy (DMD) is the most common lethal inherited disorder worldwide. Despite the exponential increase in our understanding of the disorder since the discovery and characterization of the causative gene and its product dystrophin in 1987, current therapeutic management remains largely supportive. Awaiting a final genetic cure to be available in the future, further investments in developing better drug therapies for DMD remain important. The effect of a high dose prednisone regimen will be evaluated in comparison to a daily dose regimen in a multi-center, randomized, double-blind placebo-controlled 4-arm study. Ambulant children aged 4-10 years with an established DMD diagnosis will be studied.

OPENING/CLOSING DATES: Currently enrolling, expecting to finish enrollment end 7/2005; closing 7/2005

TARGET NUMBER OF PARTICIPANTS:

140

RECRUITMENT STATUS: open

ELIGIBILITY REQUIREMENTS:

Subject Inclusion Criteria

1. 4 to 10 years of age
2. Ambulant
3. Diagnosis of DMD confirmed by at least one of the following:
   • 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 OR
   • 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 OR
   • 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.
4. Steroid naive
5. Evidence of muscle weakness by MRC score or clinical functional evaluation
6. Ability to provide reproducible repeat QMT bicep score within 15% of first assessment score
7. Ability to swallow tablets

Subject Exclusion Criteria

1. Failure to achieve one or more of the inclusion criteria listed above
2. History of significant concomitant illness or significant impairment of renal or hepatic function, or other contraindication to steroid therapy
3. Symptomatic DMD carrier
4. Positive PPD
5. Lack of prior exposure to chickenpox or immunization
6. Use of carnitine, glutamine, Coenzyme Q10, other amino acids or any herbal medications within the last 3 months
7. History of symptomatic cardiomyopathy
8. Prior attainment of quota for the age group in which the patient belongs

MAIN SPONSORING LOCATION/CONTACT:

Project Manager:
Lauren Morgenroth
University of Pittsburgh
203 Lothrop Street BST S-519
Pittsburgh, PA 15213
Tel: (412) 383-7207
Fax: (412) 648-8081
Email: lpm6@pitt.edu

ADDITIONAL LOCATION(S)/CONTACT(S):

US-SITES:

- District of Columbia
Children’s National Medical Center (CNMC)
Center for Genetic Medicine
111 Michigan Ave, NW
Washington, DC 20010

PI and Medical Director: Diana M. Escolar, MD
Erik K. Henricson, MPH
Coordinator: Angela Zimmerman azimmerman@cnmcresearch.org

- Virginia
Children’s Hospital of Virginia
Motion Analysis Laboratory
2924 Brook Road
Richmond, VA 23220-1298

PI: Eugenio Monasterio, MD
CE: Jill Mayhew, PT
Coordinator: Barbara Grillo bgrillo@chva.org

- Pennsylvania
University of Pittsburgh
S-520 Biomedical Science Tower South
Department of Neurology
Pittsburgh, PA 15213

PI: Paula Clemens, MD
PI: Henry Wessel, MD
Coordinator and Project Manager: Lauren Morgenroth  lpm6@pitt.edu 

- Minnesota

Minneapolis, MN

PI: John Day, M.D.
Coordinator: Susan Rolandelli rolan010@umn.edu 

- Texas

Dallas, TX

PI: Susan Iannaccone, MD
Coordinator: Betsy Teitell betsy.teitell@tsrh.org

- California

University of California-Davis
Sacramento, CA

PI: Craig McDonald, MD
PI: Ted Abresch, MS
Coordinator: Michelle Cregan michelle.cregan@ucdmc.ucdavis.edu

- Tennessee

University of Tennessee-Memphis
930 Madison Ave- 6th Floor
Memphis, TN 38163

PI: Tulio Bertorini, MD
Coordinator: Hani Rashed hrashed@utmem.edu

- Missouri

Washington University-St. Louis
660 S. Euclid
St. Louis, MO 63110

PI: Anne Connolly, MD
CE: Julaine Florence, PhD
Alan Pestronk, MD
Coordinator: Charlie Wulf harperc@neuro.wustl.edu        

NON-US Sites:

Melbourne, Australia
Children’s Hospital of Melbourne-Australia
Royal Children
Parkville Victoria 3052
Australia

PI: Andrew Kornberg, MD
Coordinator: Kate Carroll kate.carroll@rch.org.au

Chennai, India
Sundram Medical Foundation
600 040 Chennai India

PI: V. Vishwanathan, MD
Coordinator: Vijay Anaud, MD doctorvijay2@gmail.com 

Jerusalem, Israel

PI: Yoram Nevo, MD
Coordinator: Sharona Katzenellenbogen skatzen@attglobal.net

Recruiting

FUNDING (Agencies, Pharmaceutical Companies, etc.):

Foundation to Eradicate Duchenne (FED)

IRB and FDA APPROVAL:

yes

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