The cooperative international neuromuscular research group duchenne natural history study—a longitudinal investigation in the era of glucocorticoid therapy: Design of protocol and the methods used

Authors

  • Craig M. McDonald MD,

    Corresponding author
    • Department of Physical Medicine & Rehabilitation, School of Medicine, University of California, Sacramento, California, USA
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    • C.M.M. is the study's principal investigator. E.K.H., R.T.A., and A.C. are study chairs.

  • Erik K. Henricson MPH,

    1. Department of Physical Medicine & Rehabilitation, School of Medicine, University of California, Sacramento, California, USA
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  • R. Ted Abresch MS,

    1. Department of Physical Medicine & Rehabilitation, School of Medicine, University of California, Sacramento, California, USA
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  • Jay J. Han MD,

    1. Department of Physical Medicine & Rehabilitation, School of Medicine, University of California, Sacramento, California, USA
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  • Diana M. Escolar MD,

    1. Department of Neurology, Kennedy Krieger Institute, Baltimore, Maryland, USA
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  • Julaine M. Florence DPT,

    1. Department of Neurology, Washington University, St. Louis, Missouri, USA
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  • Tina Duong MPT,

    1. Center for Genetic Medicine Research, Children*#x00027;s National Medical Center, Washington, DC, USA
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  • Adrienne Arrieta MS,

    1. Center for Genetic Medicine Research, Children*#x00027;s National Medical Center, Washington, DC, USA
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  • Paula R. Clemens MD,

    1. Department of Neurology, University of Pittsburgh and Department of Veterans Affairs Medical Center, Pittsburgh, Pennsylvania, USA
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  • Eric P. Hoffman PhD,

    1. Center for Genetic Medicine Research, Children*#x00027;s National Medical Center, Washington, DC, USA
    2. Department of Integrative Systems Biology, George Washington University, Washington, DC, USA
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  • Avital Cnaan PhD,

    1. Center for Genetic Medicine Research, Children*#x00027;s National Medical Center, Washington, DC, USA
    2. Departments of Pediatrics, Epidemiology, and Biostatistics, George Washington University, Washington, DC, USA
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  • the Cinrg Investigators

    1. Department of Neurology, Sundaram Medical Foundation and Apollo Children-s Hospital, Chennai, India
    2. Department of Paediatrics, Holland Bloorview Kids Rehabilitation Hospital, Toronto, Ontario, Canada
    3. Division of Pediatric Neurology, Alberta Children-s Hospital, Calgary, Alberta, Canada
    4. Department of Pediatrics, University of Gothenburg, Queen Silvia Children's Hospital, Goteborg, Sweden
    5. Department of Neurology, Royal Children's Hospital, Melbourne, Victoria, Australia
    6. Neuropediatric Unit, Hadassah Hebrew University Hospital, Jerusalem, Israel
    7. Department of Neurology, Instituto de Neurosciencias Fundacion Favaloro, Buenos Aires, Argentina
    8. Departments of Neurology and Physical Medicine & Rehabilitation, Mayo Clinic, Rochester, Minnesota, USA
    9. Department of Neurology, Children's Hospital, Virginia, USA
    10. Department of Neurology, University of Tennessee, Memphis, Tennessee, USA
    11. Institute for Neuroscience and Muscle Research, Children's Hospital at Westmead, Sydney, New South Wales, Australia
    12. Division of Neurosciences, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
    13. Department of Neurology, University of Puerto Rico, San Juan, Puerto Rico
    14. Department of Child Neurology and Psychiatry, IRCCS C. Mondino, University of Pavia, Italy and Neuromuscular Omnicentre (NEMO), Milan, Italy
    15. Department of Pediatrics, Neurology and Developmental Neuroscience, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas, USA
    16. Department of Neurology, University of Minnesota, Minneapolis, Minnesota, USA
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  • This project was funded through grants from the U.S. Department of Education/NIDRR (H133B031118 and H133B090001), U.S. Department of Defense (W81XWH-09-1-0592), the National Institutes of Health (UL1RR031988, U54HD053177, UL1RR024992, U54RR026139, G12RR003051, 1R01AR061875, and RO1AR062380), and Parent Project Muscular Dystrophy.

  • Disclosures: The authors take full responsibility for the contents of this article, which do not represent the views of the U.S. Department of Education, the National Institutes of Health, the Department of Veterans Affairs, or the U.S. Government. R.T.A. has served as a consultant for PTC Therapeutics, Inc. A.A. has nothing to disclose. P.R.C. is a consultant for ReveraGen Biopharma. A.C. serves as a consultant for GlaxoSmithKline. T.D. has nothing to disclose. D.M.E. serves on the speakers bureau for and has received funding for travel and speaker honoraria from Athena Diagnostics, Inc., and also serves as a consultant for Acceleron Pharma, HALO Therapeutics, AVI Biopharma, the Gerson Lehman Group, and Medacorp. J.M.F. serves on a scientific advisory board for Prosensa, serves on the editorial board of Neuromuscular Disorders, and serves/has served as a member of the CINRG Executive Committee and as a consultant for Prosensa, GlaxoSmithKline, Genzyme Corporation, PTC Therapeutics, Inc., and Acceleron Pharma. E.K.H. is a member of the CINRG Executive Committee and has served as a consultant for Genzyme Corporation and PTC Therapeutics, Inc. J.J.H. has nothing to disclose. E.P.H. has served on advisory committees for AVI BioPharma, Inc., and as a consultant with Gerson Lehman Group, Medacorp, and Lazard Capital, and is a cofounder, board member, and shareholder of ReveraGen Biopharma. C.M.M has served on advisory committees for PTC Therapeutics, Inc., Sarepta Therapeutics, Inc., GlaxoSmithKline, plc, Prosensa, Halo Therapeutics, Shire HGT, and Novartis AG.

Correspondence to: C.M. McDonald; e-mail: cmmcdonald@ucdavis.edu

ABSTRACT

Contemporary natural history data in Duchenne muscular dystrophy (DMD) is needed to assess care recommendations and aid in planning future trials.

Methods

The Cooperative International Neuromuscular Research Group (CINRG) DMD Natural History Study (DMD-NHS) enrolled 340 individuals, aged 2–28 years, with DMD in a longitudinal, observational study at 20 centers. Assessments obtained every 3 months for 1 year, at 18 months, and annually thereafter included: clinical history; anthropometrics; goniometry; manual muscle testing; quantitative muscle strength; timed function tests; pulmonary function; and patient-reported outcomes/health-related quality-of-life instruments.

Results

Glucocorticoid (GC) use at baseline was 62% present, 14% past, and 24% GC-naive. In those ≥6 years of age, 16% lost ambulation over the first 12 months (mean age 10.8 years).

Conclusions

Detailed information on the study methodology of the CINRG DMD-NHS lays the groundwork for future analyses of prospective longitudinal natural history data. These data will assist investigators in designing clinical trials of novel therapeutics. Muscle Nerve, 2013

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