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CSM (Cervical spondylotic myelopathy) is the most common cause of spinal cord injury worldwide. While there is evidence from the recently completed SpineNet prospective study that surgical decompression is an effective treatment for CSM, it is clear that many patients have remaining neurological impairment. While surgery is relatively safe, approximately 3% of patients maintain a neurological problem. Given this background and data from preclinical models of non-traumatic and traumatic spinal cord injury, there is strong evidence to consider the potential benefit of adding a neuroprotective drug which aids in the treatment of patients with CSM whom are undergoing surgical decompression. Riluzole is FDA-approved for the treatment of amyotrophic lateral sclerosis, which has some similar clinical features to CSM. Riluzole is currently under investigation for traumatic spinal cord injury. Given this background, there is a strong basis to consider studying the potential neurological benefits of Riluzole as a treatment to surgical decompression in patients with CSM.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Placebo medication and decompressive cervical spine surgery |
|
| Riluzole | Experimental | Riluzole in dose 50mg BID for 14 days prior to surgery and 28 days after the decompressive spine surgery |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| riluzole | Drug | 50mg BID orally for 14 days prior to surgery and 28 days after the surgery |
|
| Measure | Description | Time Frame |
|---|---|---|
| Modified Japanese Orthopedic Association Score (mJOA) | The mJOA is a clinician administered scale. It evaluates four clinical dimensions; motor dysfunction score for upper and lower extremities, sensation loss and sphincter dysfunction. The total score ranges from 0 (worst) to 18 (best). | Before the surgery, 180 days |
| Measure | Description | Time Frame |
|---|---|---|
| Nurick Score | Nurick score is a simple measure of neurological dysfunction and ranges from 0 (best) to 6 (worst). | Pre-surgical, 180 days |
| SF-36v2.0 | The SF36v2.0 is a health-related quality of life instrument that evaluates health status accross eight health dimensions. |
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Inclusion Criteria:
Age between 18 and 80 years
Diagnosis of symptomatic cervical spondylotic myelopathy defined as a combination of:
one or more of the following symptoms:
one or more of the following signs:
MRI evidence of cervical spondylotic myelopathy
Scheduled for an elective surgery for cervical spondylotic myelopathy
Preoperative mJOA score ≥8 and ≤14
Women of child bearing potential must be:
Exclusion Criteria:
Inhibitors:
Inducers:
Montelukast
Phenytoin
*Note: no washout period required; if these medications are discontinued, subjects are eligible to be enrolled in the trial.
Systemic infection such as AIDS, HIV, and active hepatitis
Active malignancy defined as history of invasive malignancy, except if the patient has received treatment and displayed no clinical signs and symptoms for at least five years
Recent history (less than 3 years) of chemical substance dependency or significant psychosocial disturbance that may impact the outcome or study participation
Breastfeeding at screening visit and plan to continue during the course of the study drug
Unlikely to comply with the follow-up evaluation schedule
Unlikely to comply with investigational drug regime
Participation in a clinical trial of another investigational drug or device within the past 30 days
Is a prisoner
Unable to converse, read or write English at elementary school level
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| Name | Affiliation | Role |
|---|---|---|
| Michael Fehlings, MD | University Health Network, Toronto | Principal Investigator |
| Branko Kopjar, MD | University of Washington | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Barrow Neurological Institute | Phoenix | Arizona | 85013 | United States | ||
| UC Davis Spine Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23962993 | Background | Fehlings MG, Wilson JR, Karadimas SK, Arnold PM, Kopjar B. Clinical evaluation of a neuroprotective drug in patients with cervical spondylotic myelopathy undergoing surgical treatment: design and rationale for the CSM-Protect trial. Spine (Phila Pa 1976). 2013 Oct 15;38(22 Suppl 1):S68-75. doi: 10.1097/BRS.0b013e3182a7e9b0. | |
| 41086299 |
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| Placebo medication | Drug | 50mg BID orally for 14 days prior to surgery and 28 days after the surgery |
|
| Before the surgery, 180 days |
| Neck Disability Index (NDI) | The NDI evaluates patient self-reported functional outcomes related to neck conditions. The NDI score ranges from 0 (best) to 100 (worst). | Before the surgery, 180 days |
| Cervical Pain Numeric Rating Scale | Simple numeric rating scale with choises of answers from 0 (no pain) to 10 (worst imaginable pain) | Before the surgery, 180 days |
| EQ-5D | EQ-5Dâ„¢ is a standardised instrument for use as a measure of health outcome. It provides a simple descriptive profile and a single index value for health status. | Before the surgery, 180 days |
| American Spinal Injury Association Score (ASIA) | The ASIA impairment scale describes a person's functional impairment as a result of their spinal cord injury. | Before the surgery, 180 days |
| Sacramento |
| California |
| 95816 |
| United States |
| University of California - San Francisco | San Francisco | California | 94143 | United States |
| Emory University School of Medicine | Atlanta | Georgia | 30329 | United States |
| Rush University Medical Center | Chicago | Illinois | 60612 | United States |
| Kansas University Medical Center | Kansas City | Kansas | 66160 | United States |
| Louisiana State University | Baton Rouge | Louisiana | 70803 | United States |
| Mayo Clinic | Rochester | Minnesota | 55905 | United States |
| Washington University Orthopaedics | St Louis | Missouri | 63110 | United States |
| The Ohio State University | Columbus | Ohio | 43210 | United States |
| Rothman Institute Orthopaedics | Philadelphia | Pennsylvania | 19107 | United States |
| Thomas Jefferson University | Philadelphia | Pennsylvania | 19107 | United States |
| University of Utah | Salt Lake City | Utah | 84108 | United States |
| University of Virginia | Charlottesville | Virginia | 22908 | United States |
| Harborview Medical Center | Seattle | Washington | 98104 | United States |
| University of Calgary | Calgary | Alberta | T2N-2T9 | Canada |
| St. Michael's Hospital | Toronto | Ontario | M5B 1W8 | Canada |
| University of Toronto Hospital | Toronto | Ontario | M5T 2S8 | Canada |
| McGill University Health Centre | Montral | Quebec | H3H 2L9 | Canada |
| Montreal Neurological Institute | Montreal | Quebec | H3A 2B4 | Canada |
| University of Saskatchewan, Royal University Hospital | Saskatoon | Saskatchewan | S7N 0W8 | Canada |
| Bak AB, Moghaddamjou A, Arnold PM, Harrop JS, Fehlings MG. Chronic pain after decompression for degenerative cervical myelopathy: a pooled trajectory analysis of individual participant data. Pain. 2026 Mar 1;167(3):654-662. doi: 10.1097/j.pain.0000000000003828. Epub 2025 Oct 15. |
| 40347099 | Derived | Wong R, Alvi MA, Quddusi AI, Fehlings MG. Role of Neck Pain in Defining Clinical Trajectories of Outcomes in Patients With Degenerative Cervical Myelopathy: Results of a Novel Machine Learning Algorithm. Global Spine J. 2026 Jan;16(1):218-229. doi: 10.1177/21925682251341263. Epub 2025 May 10. |
| 38197642 | Derived | Pedro KM, Alvi MA, Hejrati N, Moghaddamjou A, Fehlings MG. Elderly Patients Show Substantial Improvement in Health-Related Quality of Life After Surgery for Degenerative Cervical Myelopathy Despite Medical Frailty: An Ambispective Analysis of a Multicenter, International Data Set. Neurosurgery. 2024 Jan 10. doi: 10.1227/neu.0000000000002818. Online ahead of print. |
| 33357512 | Derived | Fehlings MG, Badhiwala JH, Ahn H, Farhadi HF, Shaffrey CI, Nassr A, Mummaneni P, Arnold PM, Jacobs WB, Riew KD, Kelly M, Brodke DS, Vaccaro AR, Hilibrand AS, Wilson J, Harrop JS, Yoon ST, Kim KD, Fourney DR, Santaguida C, Massicotte EM, Kopjar B. Safety and efficacy of riluzole in patients undergoing decompressive surgery for degenerative cervical myelopathy (CSM-Protect): a multicentre, double-blind, placebo-controlled, randomised, phase 3 trial. Lancet Neurol. 2021 Feb;20(2):98-106. doi: 10.1016/S1474-4422(20)30407-5. Epub 2020 Dec 22. |
| ID | Term |
|---|---|
| D019782 | Riluzole |
| ID | Term |
|---|---|
| D013844 | Thiazoles |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D052160 | Benzothiazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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