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

• Published in: Muscle & nerve Vol. 49; no. 2; pp. 187 - 192
• Main Authors: Kissel, John T., Elsheikh, Bakri, King, Wendy M., Freimer, Miriam, Scott, Charles B., Kolb, Stephen J., Reyna, Sandra P., Crawford, Thomas O., Simard, Louise R., Krosschell, Kristin J., Acsadi, Gyula, Schroth, Mary K., D'Anjou, Guy, LaSalle, Bernard, Prior, Thomas W., Sorenson, Susan, Maczulski, Jo Anne, Swoboda, Kathryn J.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.02.2014; Wiley Subscription Services, Inc
• Subjects: Adult; Ambulatory Care; carnitine; Cohort Studies; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Female; Histone Deacetylase Inhibitors - pharmacology; Histone Deacetylase Inhibitors - therapeutic use; Humans; Male; Middle Aged; motor neuron disease; Muscle Contraction - drug effects; Muscle Contraction - physiology; Muscle Strength - drug effects; Muscle Strength - physiology; Muscular Atrophy, Spinal - drug therapy; Muscular Atrophy, Spinal - physiopathology; Muscular system; Prospective Studies; spinal muscular atrophy; Treatment Outcome; valproic acid; Valproic Acid - pharmacology; Valproic Acid - therapeutic use
• ISSN: 0148-639X; 1097-4598; 1097-4598
• DOI: 10.1002/mus.23904

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