Riluzole for the treatment of acute traumatic spinal cord injury: rationale for and design of the NACTN Phase I clinical trial

• Published in: Journal of neurosurgery. Spine Vol. 17; no. 1 Suppl; pp. 151 - 156
• Main Authors: FEHLINGS, Michael G, WILSON, Jefferson R, BURAU, Keith D, JOHNSON, Michele W, GROSSMAN, Robert G, FRANKOWSKI, Ralph F, TOUPS, Elizabeth G, AARABI, Bizhan, HARROP, James S, SHAFFREY, Christopher I, HARKEMA, Susan J, GUEST, James D, TATOR, Charles H
• Format: Journal Article
• Language: English
• Published: Charlottesville, VA American Association of Neurological Surgeons 01-09-2012
• Subjects: Biological and medical sciences; Humans; Medical sciences; Neuroprotective Agents - therapeutic use; Neurosurgery; Orthopedic surgery; Research Design; Riluzole - therapeutic use; Spinal Cord Injuries - drug therapy; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; clinical trial; spinal cord injury; Nervous system diseases; Treatment; American; Spinal cord trauma; Central nervous system disease; Phase I trial; North; North American Clinical Trials Network; Spinal cord disease; Riluzole
• ISSN: 1547-5654; 1547-5646
• DOI: 10.3171/2012.4.aospine1259

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.