title: A randomized controlled phase II trial of riluzole in early multiple sclerosis.
abstract: OBJECTIVE
  We evaluated the effect of riluzole versus placebo added to weekly IM interferon beta-1a in early multiple sclerosis (MS).
  
  
  METHODS
  This is a randomized (1:1), double-blind, placebo-controlled trial of riluzole 50 mg twice daily in subjects with MS onset less than 1 year prior. Trial participation was up to 3 years. The primary endpoint was change in percent brain volume change. Secondary endpoints included changes in normalized gray and normal-appearing white matter volumes, retinal nerve fiber layer thickness (RNFL), MS Functional Composite and Symbol Digit Modalities Test scores. Mixed model regression analysis was used to compare the changes over time between groups.
  
  
  RESULTS
  Forty-three subjects were randomized to study drug (22 riluzole, 21 placebo). Baseline characteristics were overall similar between groups except for older age (P = 0.042), higher normalized cerebrospinal fluid volume (P = 0.050), lower normalized gray matter volume (P = 0.14), and thinner RNFL (P = 0.043) in the riluzole group. In the primary analysis, percent brain volume change in the placebo group decreased at a rate of 0.49% per year whereas the riluzole group decreased by 0.86% per year (0.37% more per year; 95% CI -0.78, 0.024; P = 0.065). Although age did not influence the rate of brain volume decline, the difference between groups was attenuated after adjustment for baseline normalized gray matter and lesion volume (0.26% more per year in riluzole group; 95% CI -0.057, 0.014; P = 0.22). Analyses of secondary outcomes showed no differences between groups.
  
  
  CONCLUSIONS
  This trial provides class 1 evidence that riluzole treatment does not meaningfully reduce brain atrophy progression in early MS.
authors.affiliation: MS Center, Neurology Department, University of California San Francisco San Francisco, California ; Department of Pediatrics, University of California San Francisco San Francisco, California.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Waubant
authors.affiliation: MS Center, Neurology Department, University of California San Francisco San Francisco, California.
authors.forename: Amir-Hadi
authors.initials: AH
authors.lastname: Maghzi
authors.affiliation: MS Center, Neurology Department, University of California San Francisco San Francisco, California.
authors.forename: Nisha
authors.initials: N
authors.lastname: Revirajan
authors.affiliation: Portland VA Medical Center & Oregon Health & Science University Portland, Oregon.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Spain
authors.affiliation: MS Center, Neurology Department, University of California San Francisco San Francisco, California.
authors.forename: Laura
authors.initials: L
authors.lastname: Julian
authors.affiliation: Department of Neurology, Hopkins MS Center Baltimore, Maryland.
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Mowry
authors.affiliation: MS Center, Neurology Department, University of California San Francisco San Francisco, California.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Marcus
authors.affiliation: Department of Neurology, Yale University School of Medicine New Haven, Connecticut.
authors.forename: Shuang
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Epidemiology and Biostatistics, University of California San Francisco San Francisco, California.
authors.forename: Chengshi
authors.initials: C
authors.lastname: Jin
authors.affiliation: MS Center, Neurology Department, University of California San Francisco San Francisco, California ; Department of Ophthalmology, University of California San Francisco San Francisco, California.
authors.forename: Ari
authors.initials: A
authors.lastname: Green
authors.affiliation: Department of Epidemiology and Biostatistics, University of California San Francisco San Francisco, California.
authors.forename: Charles E
authors.initials: CE
authors.lastname: McCulloch
authors.affiliation: Department of Neurology, Yale University School of Medicine New Haven, Connecticut.
authors.forename: Daniel
authors.initials: D
authors.lastname: Pelletier