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

Muscle Nerve. 2014 Feb;49(2):187-92. 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.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Ambulatory Care
  • 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
  • Muscle Contraction / drug effects
  • Muscle Contraction / physiology
  • Muscle Strength / drug effects
  • Muscle Strength / physiology
  • Muscular Atrophy, Spinal / drug therapy*
  • Muscular Atrophy, Spinal / physiopathology*
  • Prospective Studies
  • Treatment Outcome
  • Valproic Acid / pharmacology
  • Valproic Acid / therapeutic use*

Substances

  • Histone Deacetylase Inhibitors
  • Valproic Acid