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

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.

• Authors: John T Kissel, Bakri Elsheikh, Wendy M King, Miriam Freimer, Charles B Scott, Stephen J Kolb, Sandra P Reyna, Thomas O Crawford, Louise R Simard, Kristin J Krosschell, Gyula Acsadi, Mary K Schroth, Guy D'Anjou, Bernard LaSalle, Thomas W Prior, Susan Sorenson, Jo Anne Maczulski, Kathryn J Swoboda, Project Cure Spinal Muscular Atrophy Investigators Network
• Journal: Muscle & nerve (Muscle Nerve) Vol. 49 Issue 2 Pg. 187-92 (Feb 2014) ISSN: 1097-4598 [Electronic] United States
• PMID: 23681940 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Histone Deacetylase Inhibitors
• Valproic Acid

Topics

• Adult
• Ambulatory Care
• Cohort Studies
• Cross-Over Studies
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Histone Deacetylase Inhibitors (pharmacology, therapeutic use)
• Humans
• Male
• Middle Aged
• Muscle Contraction (drug effects, physiology)
• Muscle Strength (drug effects, physiology)
• Muscular Atrophy, Spinal (drug therapy, physiopathology)
• Prospective Studies
• Treatment Outcome
• Valproic Acid (pharmacology, therapeutic use)