Study Design. Descriptive article and narrative review.
Objective. To explain the rationale and design of the cervical spondylotic myelopathy (CSM)-Protect clinical trial that aims to elucidate the efficacy and safety of riluzole in the context of CSM.
Summary of Background Data. CSM is the most common cause of spinal cord–related dysfunction internationally. Although surgery is effective in preventing the progression of impairment, and in some cases improving functional outcomes, many patients continue to exhibit significant disability in the postoperative setting. Evidence from preclinical studies suggests that glutamate-related excitotoxicity may contribute to the pathology of CSM and that administration of the sodium and glutamate-blocking medication riluzole, when combined with spinal cord decompression, may mitigate this effect and improve neurobehavioral outcomes. Although riluzole is FDA approved and has been shown to be safe and effective in the context of amyotrophic lateral sclerosis, its efficacy and safety in the context of CSM remain unknown.
Methods. Descriptive article with narrative review of the literature.
Results. In addition to providing pertinent preclinical background on the topic, this descriptive article and narrative review discusses the design and current status of an ongoing phase III randomized controlled trial evaluating the efficacy and safety of riluzole, combined with surgical decompression, in the treatment of CSM.
Conclusion. On the basis of current projections, we estimate that the interim analysis for this study will take place in the spring of 2014, at which time an adaptive sample size adjustment may take place.
This descriptive article narrative review discusses the preclinical rationale for and design of a phase III trial currently underway to investigate the efficacy of the sodium and glutamate-blocking medication riluzole, combined with surgical decompression, in the treatment of cervical spondylotic myelopathy.
*Department of Surgery, Division of Neurosurgery and Spinal Program, University of Toronto, Toronto Western Hospital, Toronto, Ontario, Canada
†Department of Neurosurgery, University of Kansas, Kansas City, KS; and
‡Department of Health Services, University of Washington, Seattle, WA.
Address correspondence and reprint requests to Michael G. Fehlings, MD, PhD, FRCSC, FACS, University of Toronto, 399 Bathurst St, Toronto Western Hospital, Toronto, Ontario Canada; E-mail: Michael.Fehlings@uhn.on.ca
Acknowledgment date: March 6, 2013. First revision date: May 28, 2013. Acceptance date: July 12, 2013.
The manuscript submitted does not contain information about medical device(s)/drug(s).
Supported by AOSpine North America, Inc. Analytic support for this work was provided by Spectrum Research, Inc., with funding from the AOSpine North America.
Relevant financial activities outside the submitted work: consulting fee or honorarium, consultancy, grants/grants pending and travel/accommodations/meeting expenses.