A prospective, multicenter, phase I matched-comparison group trial of safety, pharmacokinetics, and preliminary efficacy of riluzole in patients with traumatic spinal cord injury.

Authors

Robert G Grossman, Department of Neurosurgery, Houston Methodist Hospital, Houston Methodist Research InstituteFollow
Michael G Fehlings, Department of Surgery, Division of Neurosurgery and Spine Program, University of TorontoFollow
Ralph F Frankowski, Division of Biostatistics, University of Texas School of Public HealthFollow
Keith D Burau, Division of Biostatistics, University of Texas School of Public Health
Diana S L Chow, Department of Pharmacological and Pharmaceutical Sciences, University of Houston
Charles Tator, Department of Surgery, Division of Neurosurgery and Spine Program, University of TorontoFollow
Angela Teng, Department of Pharmacological and Pharmaceutical Sciences, University of Houston
Elizabeth G Toups, Department of Neurosurgery, Houston Methodist Hospital, Houston Methodist Research Institute
James Harrop, Department of Neurosurgery, Thomas Jefferson UniversityFollow
Bizhan Aarabi, Department of Neurosurgery, University of MarylandFollow
Christopher I Shaffrey, Department of Neurosurgery, University of VirginiaFollow
Michele M Johnson, Department of Neurosurgery, University of Texas Health Science Center
Susan J Harkema, Department of Neurosurgery, University of LouisvilleFollow
Maxwell Boakye, Department of Neurosurgery, University of Louisville
James D GuestFollow
Jefferson R Wilson, Department of Surgery, Division of Neurosurgery and Spine Program, University of TorontoFollow

Document Type

Article

Publication Date

2-1-2014

Comments

This article has been peer reviewed. It was published in: Journal of Neurotrauma.

Volume 31, Issue 3, 1 February 2014, Pages 239-255.

The published version is available at DOI: 10.1089/neu.2013.2969

Copyright © 2014, Mary Ann Liebert, Inc.

Abstract

A prospective, multicenter phase I trial was undertaken by the North American Clinical Trials Network (NACTN) to investigate the pharmacokinetics and safety of, as well as obtain pilot data on, the effects of riluzole on neurological outcome in acute spinal cord injury (SCI). Thirty-six patients, with ASIA impairment grades A-C (28 cervical and 8 thoracic) were enrolled at 6 NACTN sites between April 2010 and June 2011. Patients received 50 mg of riluzole PO/NG twice-daily, within 12 h of SCI, for 14 days. Peak and trough plasma concentrations were quantified on days 3 and 14. Peak plasma concentration (Cmax) and systemic exposure to riluzole varied significantly between patients. On the same dose basis, Cmax did not reach levels comparable to those in patients with amyotrophic lateral sclerosis. Riluzole plasma levels were significantly higher on day 3 than on day 14, resulting from a lower clearance and a smaller volume of distribution on day 3. Rates of medical complications, adverse events, and progression of neurological status were evaluated by comparison with matched patients in the NACTN SCI Registry. Medical complications in riluzole-treated patients occurred with incidences similar to those in patients in the comparison group. Mild-to-moderate increase in liver enzyme and bilirubin levels were found in 14-70% of patients for different enzymes. Three patients had borderline severe elevations of enzymes. No patient had elevated bilirubin on day 14 of administration of riluzole. There were no serious adverse events related to riluzole and no deaths. The mean motor score of 24 cervical injury riluzole-treated patients gained 31.2 points from admission to 90 days, compared to 15.7 points for 26 registry patients, a 15.5-point difference (p=0.021). Patients with cervical injuries treated with riluzole had more-robust conversions of impairment grades to higher grades than the comparison group.

Recommended Citation

Grossman, Robert G; Fehlings, Michael G; Frankowski, Ralph F; Burau, Keith D; Chow, Diana S L; Tator, Charles; Teng, Angela; Toups, Elizabeth G; Harrop, James; Aarabi, Bizhan; Shaffrey, Christopher I; Johnson, Michele M; Harkema, Susan J; Boakye, Maxwell; Guest, James D; and Wilson, Jefferson R, "A prospective, multicenter, phase I matched-comparison group trial of safety, pharmacokinetics, and preliminary efficacy of riluzole in patients with traumatic spinal cord injury." (2014). Department of Neurosurgery Faculty Papers. Paper 72.
https://jdc.jefferson.edu/neurosurgeryfp/72

PubMed ID

23859435