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

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  • 1 Department of Surgery, Division of Neurosurgery and Spinal Program, University of Toronto, Toronto Western Hospital, Toronto, Ontario, Canada;
  • | 2 Division of Biostatistics, University of Texas School of Public Health at Houston;
  • | 3 Department of Neurosurgery, The Methodist Hospital, Houston, Texas;
  • | 4 Department of Neurosurgery, University of Maryland, Baltimore, Maryland;
  • | 5 Department of Neurosurgery and Orthopedic Surgery, Division of Spinal Disorders, Thomas Jefferson University, Philadelphia, Pennsylvania;
  • | 6 Departments of Neurological Surgery and Orthopedic Surgery, University of Virginia Health System, Charlottesville, Virginia;
  • | 7 Department of Neurosurgery, University of Kentucky, Louisville, Kentucky;
  • | 8 Department of Neurosurgery and Miami Project to Cure Paralysis, University of Miami, Florida; and
  • | 9 Department of Neurosurgery, University of Texas Health Sciences Center, Houston, Texas
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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.

Abbreviations used in this paper:

ALS = amyotrophic lateral sclerosis; ASIA = American Spinal Injury Association; NACTN = North American Clinical Trials Network for Treatment of Spinal Cord Injury; SCI = spinal cord injury.

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