Riluzole in Acute Spinal Cord Injury—RISCIS

05. September 2016

A Multi-Center, Randomized, Placebo Controlled, Double-Blinded Trial of Efficacy and Safety.

​Spinal cord injury (SCI) results in devastating physical impairment and is associated with significant costs to the individual and to society. There is compelling evidence that the pathobiology of SCI involves an initial primary mechanical injury which is amplified by a complex series of secondary injury events including ischemia, ion channel dysfunction, glutamatergic excitoxicity and apoptosis. Riluzole, a sodium-glutamate antagonist, which is approved as a treatment to attenuate the rate of nerve cell degeneration in amyotrophic lateral sclerosis (ALS), has shown considerable promise as a therapeutic strategy to enhance outcomes in preclinical models of traumatic and non-traumatic SCI.  A few years ago, AOSpine North America, led by principal investigator Dr. Michael Fehlings (chair of the AOSpine SCI Knowledge Forum and past chair of AOSpine North America) set out to obtain clinical evidence on the safety and efficacy of the drug riluzole in improving outcomes after spinal cord injury (SCI) in patients. Further proof supporting its safety when delivered to patients immediately following injury had been obtained in a U.S. Department of Defense-funded phase I/IIa clinical trial (undertaken by the North American Clinical Trials Network-NACTN, in partnership with AOSpine) between 2010 and 2011 in which many AOSpine North America members participated as investigators. This Phase I/IIa prospective, cohort-controlled study also showed promising proof-of-concept data suggesting potential neuroprotective efficacy particularly after cervical SCI.

AOSpine North America’s multi-center trial was initiated in 2013 under the abbreviated title “Riluzole in Acute Spinal Cord Injury Study: RISCIS”. Since then, the trial has grown to include 22 sites across the United States, Canada and southeastern Australia. There are plans in motion to further expand the trial to additional North American sites and other regions in Australia. Spine clinician-scientists from Europe, Asia and the Middle East have also voiced their interest in joining this collaborative international research effort.

The RISCIS trial is now a combined project supported by the following entities: AOSpine North America, AOSpine International, Christopher and Dana Reeve Foundation’s North American Clinical Trial Network (NACTN), Ontario Neurotrauma Foundation, U.S. Department of Defense and Rick Hansen Institute. In recognition of the potential significant impact that RISCIS may have on SCI treatment, the participating sites and principal investigators have all agreed to subsidize many of their internal costs in order to be able to participate in the study. Their willingness to contribute their own time and funds has technically made this a study with more than 25 sponsoring organizations.

Many of the sites have taken this opportunity to initiate SCI sub-studies. These include efforts to research: MRI biomarkers in SCI, the pharmacokinetic properties of the study drug and quality assurance comparisons for patients presenting with SCI to two separate hospitals in the same health system. As of today, RISCIS has enrolled 51 subjects.

As indicated by RISCIS principal investigator Dr. Michael Fehlings (Professor of Neurosurgery at the University of Toronto), the RISCIS trial shows “considerable promise to enhance the neurological outcomes and quality of life and reduce the costs of care for individuals with acute SCI”.

AOSpine International, AOSpine North America and its collaborating partners would like to take this opportunity to thank all of the investigators, study coordinators and AO members for their continued efforts in promoting world-class SCI research through their participation in the RISCIS trial. For more information about the trial, please email RISCIS@nor-consult.com.

We look forward to bringing the AO community further updates about the trial as they become available.

The Knowledge Forum SCI

The Knowledge Forum SCI is one of the five pathology focused working groups acting on behalf of AOSpine. Chaired by Dr. Michael Fehlings, this group of international experts consists of Dr. Robert Grossman, Dr. Shekar Kurpad, Dr. James Harrop, Dr. Bizhan Aarabi and Dr. Brian Kwon. In addition to this flagship project, this group of key opinion leaders is also interested in two other areas: a) the development of evidence-based clinical guidelines for the treatment of acute spinal cord injury; b) an overall description of the SCI patient population through the extensive sample size provided from the merge of two databases (NACTN – The Christopher and Diana Reeve Foundation's North American Clinical Trials Network – PI: Robert Grossman; and STASCIS – The Surgical Trial in Acute Spinal Cord Injury Study – PI: Michael Fehlings).​​​ ​