Drug trial examines improved outcomes, reduced neurological risk of CSM surgery

Riluzole is being studied for its ability to reduce surgical decompression risk, enhance long-term neurological outcomes in patients with symptomatic CSM.

Patients are being recruited for a clinical trial of riluzole, which is FDA-approved for the treatment of amyotrophic lateral sclerosis, that is designed to determine its effectiveness in improving surgical decompression outcomes in patients with symptomatic cervical spondylotic myelopathy.

The neuroprotective drug may eventually be used intraoperatively to lessen the neurological risks and enhance long-term neurological outcomes of surgical decompression in patients with cervical spondylotic myelopathy (CSM), Michael G. Fehlings, MD, PhD, FRCSC, FACS, FRSC, said at the Spine Summit 2015: CNS/AANS Section on Disorders of the Spine & Peripheral Nerves Annual Meeting.

Fehlings discussed some of the reasons for the interest in riluzole.

Michael G. Fehlings

“Riluzole is a drug specifically developed as a nerve protective agent, in that it blocks sodium glutamate in the cell injury,” he said, noting that is one of the critical pathways in ischemic cell injury. “By way of review, riluzole blocks the sodium channels of the presynaptic neuron. It is principally a sodium channel blocker, and by doing so it also alters the sodium calcium homeostasis and reduces calcium influx.”

Neurological risks for patients

Although decompressive spinal surgery for CSM is safe, according to Fehlings, there are potential neurological risks for patients, such as nerve root problems and delayed C5 palsy. About 4% of patients who undergo such surgery will develop one of these neurological risks, he said.

Fehlings said while CSM is not necessarily cured through surgery, about 80% of patients experience improvement following treatment. On average, they have 2.5 points of improvement postoperatively in the modified Japanese Orthopaedic Association score (mJOA).

“What all this means is, wouldn’t it be great if we had a neuroprotective treatment that could substantially reduce neurological risks while giving you the decompression that could potentially attenuate the incidence and impact of a CSM fusion injury? And who knows, it might enhance the neuronal plasticity to achieve improved outcomes,” he said.

Randomization to drug or placebo

The ongoing trial, which is sponsored by AOSpine North America, is currently recruiting at 12 sites with an enrollment goal of 300 patients. It involves 1:1 randomization in which patients receive the drug for 14 days prior to decompression surgery and undergo a baseline neurologic exam just prior to surgery. They continue the drug for 4 weeks after surgery.

Control patients receive a placebo medication.

The study’s primary outcome measure is the change in mJOA scores from baseline to 6 months postoperatively. Secondary outcomes being used are the Nurick, SF-36, Neck Disability Index and EuroQol-5D pain scores, as well as an assessment of complications. According to Fehlings, the evaluations will continue through 1 year and, ultimately, investigators plan to derive economic value-based studies from these data.

May mitigate surgical risk

A futility analysis was built into the clinical trial and the study will be discontinued if riluzole has no effect on the patients in the experimental group.

“I wanted to make this group aware of what I think will be an evolving area in cervical myelopathy where we potentially may be able to make the surgery even safer and potentially, through altering the biologic processes in the injured spinal cord, have a complementary approach to decompressive surgery,” Fehlings said.

At the time of his presentation, Fehlings said 187 patients with a mean age of 58 years were enrolled in the trial. The cohort has a slight male predominance and all patients have moderate to severe myelopathy.

Enrollment is expected to be completed in June 2016. – by Robert Linnehan

Reference:
Fehlings MG. CSM-Protect trial. Presented at: Spine Summit 2015: CNS/AANS Section on Disorders of the Spine & Peripheral Nerves Annual Meeting; March 4-7, 2015; Phoenix.

For more information:
Michael G. Fehlings, MD, PhD, FRCSC, FACS, FRSC, can be reached at Toronto Western Hospital, West Wing, 4th Floor, Room 4WW449, 399 Bathurst St., Toronto, Ontario, Canada M5T 2S8; email: michael.fehlings@uhn.ca.

Disclosure: Fehlings reports he is not advocating the use of the off-label application of what is discussed in the context of the clinical trial. He reports receiving royalties from DePuy Synthes.