A randomized controlled phase II trial of riluzole in early multiple sclerosis
Article first published online: 14 APR 2014
© 2014 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.
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Annals of Clinical and Translational Neurology
Volume 1, Issue 5, pages 340–347, May 2014
How to Cite
Waubant, E., Maghzi, A.-H., Revirajan, N., Spain, R., Julian, L., Mowry, E. M., Marcus, J., Liu, S., Jin, C., Green, A., McCulloch, C. E. and Pelletier, D. (2014), A randomized controlled phase II trial of riluzole in early multiple sclerosis. Annals of Clinical and Translational Neurology, 1: 340–347. doi: 10.1002/acn3.60
- Issue published online: 13 MAY 2014
- Article first published online: 14 APR 2014
- Manuscript Accepted: 14 MAR 2014
- Manuscript Revised: 3 MAR 2014
- Manuscript Received: 26 JAN 2014
- National MS Society. Grant Number: RG 3932-A-2
- Race to Erase MS
- Nancy Davis foundation
- Sanofi Aventis and Biogen Idec
- MS International Federation
We evaluated the effect of riluzole versus placebo added to weekly IM interferon beta-1a in early multiple sclerosis (MS).
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.
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.
This trial provides class 1 evidence that riluzole treatment does not meaningfully reduce brain atrophy progression in early MS.