title: Riluzole for the treatment of acute traumatic spinal cord injury: rationale for and design of the NACTN Phase I clinical trial.
abstract: In the immediate period after traumatic spinal cord injury (SCI) a variety of secondary injury mechanisms combine to gradually expand the initial lesion size, potentially leading to diminished neurological outcomes at long-term follow-up. Riluzole, a benzothiazole drug, which has neuroprotective properties based on sodium channel blockade and mitigation of glutamatergic toxicity, is currently an approved drug that attenuates the extent of neuronal degeneration in patients with amyotrophic lateral sclerosis. Moreover, several preclinical SCI studies have associated riluzole administration with improved functional outcomes and increased neural tissue preservation. Based on these findings, riluzole has attracted considerable interest as a potential neuroprotective drug for the treatment of SCI. Currently, a Phase I trial evaluating the safety and pharmacokinetic profile of riluzole in human SCI patients is being conducted by the North American Clinical Trials Network (NACTN) for Treatment of Spinal Cord Injury. The current review summarizes the existing preclinical and clinical literature on riluzole, provides a detailed description of the Phase I trial, and suggests potential opportunities for future investigation. Clinical trial registration no.: NCT00876889.
authors.affiliation: Department of Surgery, Division of Neurosurgery and Spinal Program, University of Toronto, Toronto Western Hospital, Toronto, Ontario, Canada. Michael.Fehlings@uhn.on.ca
authors.forename: Michael G
authors.initials: MG
authors.lastname: Fehlings
authors.forename: Jefferson R
authors.initials: JR
authors.lastname: Wilson
authors.forename: Ralph F
authors.initials: RF
authors.lastname: Frankowski
authors.forename: Elizabeth G
authors.initials: EG
authors.lastname: Toups
authors.forename: Bizhan
authors.initials: B
authors.lastname: Aarabi
authors.forename: James S
authors.initials: JS
authors.lastname: Harrop
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Shaffrey
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Harkema
authors.forename: James D
authors.initials: JD
authors.lastname: Guest
authors.forename: Charles H
authors.initials: CH
authors.lastname: Tator
authors.forename: Keith D
authors.initials: KD
authors.lastname: Burau
authors.forename: Michele W
authors.initials: MW
authors.lastname: Johnson
authors.forename: Robert G
authors.initials: RG
authors.lastname: Grossman
mesh_terms: D006801:Humans; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D012107:Research Design; D019782:Riluzole / Q000627:therapeutic use*; D013119:Spinal Cord Injuries / Q000188:drug therapy*
chemical_list: D018696:Neuroprotective Agents; D019782:Riluzole