SMA valiant trial: A prospective, double-blind, placebo-controlled trial of valproic acid in ambulatory adults with spinal muscular atrophy

Authors

  • John T. Kissel MD,

    Corresponding author
    1. Department of Neurology, Division of Neuromuscular Medicine, Ohio State University, Wexner Medical Center, Columbus, Ohio, USA
    2. Department of Pediatrics, Ohio State University, Columbus, Ohio, USA
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  • Bakri Elsheikh MD,

    1. Department of Neurology, Division of Neuromuscular Medicine, Ohio State University, Wexner Medical Center, Columbus, Ohio, USA
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  • Wendy M. King PT,

    1. Department of Neurology, Division of Neuromuscular Medicine, Ohio State University, Wexner Medical Center, Columbus, Ohio, USA
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  • Miriam Freimer MD,

    1. Department of Neurology, Division of Neuromuscular Medicine, Ohio State University, Wexner Medical Center, Columbus, Ohio, USA
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  • Charles B. Scott PhD,

    1. CBS Squared, Inc., Fort Washington, Pennsylvania, USA
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  • Stephen J. Kolb MD, PhD,

    1. Department of Neurology, Division of Neuromuscular Medicine, Ohio State University, Wexner Medical Center, Columbus, Ohio, USA
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  • Sandra P. Reyna MD,

    1. Department of Neurology, University of Utah School of Medicine, Salt Lake City, Utah, USA
    2. Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah, USA
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  • Thomas O. Crawford MD,

    1. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    2. Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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  • Louise R. Simard PhD,

    1. Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba, Canada
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  • Kristin J. Krosschell PT, DPT,

    1. Department of Physical Therapy and Human Movement Sciences, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
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  • Gyula Acsadi MD, PhD,

    1. Department of Neurology, University of Connecticut School of Medicine, Hartford, Connecticut, USA
    2. Department of Pediatrics, University of Connecticut School of Medicine, Hartford, Connecticut, USA
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  • Mary K. Schroth MD,

    1. Department of Pediatrics, University of Wisconsin School of Medicine, Madison, Wisconsin, USA
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  • Guy D'Anjou MD,

    1. Division of Pediatric Neurology, Hôpital Sainte-Justine Montréal, Montréal, Québec, Canada
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  • Bernard LaSalle BS,

    1. Department of Biomedical Informatics, University of Utah School of Medicine, Salt Lake City, USA
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  • Thomas W. Prior PhD,

    1. Department of Molecular Pathology, Ohio State University, Wexner Medical Center, Columbus, Ohio, USA
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  • Susan Sorenson PharmD,

    1. Intermountain Healthcare at Primary Children's Medical Center, Salt Lake City, Utah, USA
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  • Jo Anne Maczulski MA, OTR/L,

    1. Pediatric Occupational Therapy Services, Chicago, Illinois, USA
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  • Kathryn J. Swoboda MD,

    1. Department of Neurology, University of Utah School of Medicine, Salt Lake City, Utah, USA
    2. Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah, USA
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  • for the Project Cure Spinal Muscular Atrophy Investigators Network


  • Disclosures: J.K. received drugs from Abbott Pharmaceuticals for a clinical trial in SMA, is a paid consultant for Alexion Pharmaceuticals and Cytokinetics, and is funded by the National Institutes of Health (NIH U10 NS77382-2 for NeuroNEXT). B.E. received drugs from Abbott Pharmaceuticals for a clinical trial in SMA. S.R. has received grants from Families of SMA. K.K has received grant funding from the Families of SMA. G.A. receives funding from NIH/NINDS. B.L. received grants from Families of SMA and the National Center for Research Resources (UL1RR025764 to the University of Utah Center for Clinical and Translational Science). K.S. has contracts with ISIS Pharmaceuticals, Inc., Orphamed, and Biomarin for clinical trials and receives grant support from the NIH (R01-HD69045 from NICHD and U10 NS077305 from NINDS), the Muscular Dystrophy Association, and the Alternating Hemiplegia of Childhood Foundation. The remaining authors have no disclosures to report.

ABSTRACT

Introduction: An open-label trial suggested that valproic acid (VPA) improved strength in adults with spinal muscular atrophy (SMA). We report a 12-month, double-blind, cross-over study of VPA in ambulatory SMA adults. Methods: There were 33 subjects, aged 20–55 years, included in this investigation. After baseline assessment, subjects were randomized to receive VPA (10–20 mg/kg/day) or placebo. At 6 months, patients were switched to the other group. Assessments were performed at 3, 6, and 12 months. The primary outcome was the 6-month change in maximum voluntary isometric contraction testing with pulmonary, electrophysiological, and functional secondary outcomes. Results: Thirty subjects completed the study. VPA was well tolerated, and compliance was good. There was no change in primary or secondary outcomes at 6 or 12 months. Conclusions: VPA did not improve strength or function in SMA adults. The outcomes used are feasible and reliable and can be employed in future trials in SMA adults. Muscle Nerve 49: 187–192, 2014

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