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