Efficacy of Riluzole in Surgical Treatment for Cervical Spondylotic Myelopathy (CSM-Protect)

NCT01257828 | Completed Phase 3

• 1 other identifier: SPN-10-001
• Study Type: interventional
• Target: 270
• Locations: 2 countries
• Sites: 21

Brief Summary

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.

Conditions

Cervical Spondylotic Myelopathy

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (6)

• Nurick Score

  Pre-surgical, 180 days

• SF-36v2.0

  Before the surgery, 180 days

• Neck Disability Index (NDI)

  Before the surgery, 180 days

• Cervical Pain Numeric Rating Scale

  Before the surgery, 180 days

• EQ-5D

  Before the surgery, 180 days

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo medication and decompressive cervical spine surgery

Drug: Placebo medication

Riluzole

EXPERIMENTAL

Riluzole in dose 50mg BID for 14 days prior to surgery and 28 days after the decompressive spine surgery

Drug: riluzole

Interventions

riluzole DRUG

50mg BID orally for 14 days prior to surgery and 28 days after the surgery

Also known as: Rilutek

Riluzole

Placebo medication DRUG

50mg BID orally for 14 days prior to surgery and 28 days after the surgery

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 18 and 80 years
• Diagnosis of symptomatic cervical spondylotic myelopathy defined as a combination of:
• one or more of the following symptoms:
• Numb hands
• Clumsy hands
• Impairment of gait
• Bilateral arm paresthesiae
• l'Hermitte's phenomena
• Weakness And,
• one or more of the following signs:
• Corticospinal distribution motor deficits
• Atrophy of hand intrinsic muscles
• Hyperreflexia
• Positive Hoffman sign
• Upgoing plantar responses

You may not qualify if:

• Previous surgery for CSM
• Concomitant symptomatic lumbar stenosis
• CSM symptoms due to cervical trauma (at the discretion of the investigator)
• Hypersensitivity to riluzole or any of its components
• Neutropenia measured as absolute neutrophil count (ANC) measured in cells per microliter of blood of \< 1500 at screening visit
• Creatinine level of \> 1.2 milligrams (mg) per deciliter (dl) in males or \> 1.1 milligrams per deciliter in females at screening visit Liver enzymes (ALT or AST) 3x higher than normal values at screening visit.
• Liver enzymes (ALT or AST) 3x higher than normal values at screening visit.
• Subject will be using any of the following medications which are classified as CYP1A2 inhibitors or inducers\*during the course of the drug regimen:
• Inhibitors:
• Ciprofloxacin
• Enoxacin
• Fluvoxamine
• Methoxsalen
• Mexiletine
• Oral contraceptives

Sponsors & Collaborators

• AOSpine North America Research Network: lead

Study Sites (21)

Barrow Neurological Institute

Phoenix, Arizona, 85013, United States

Location

UC Davis Spine Center

Sacramento, California, 95816, United States

Location

University of California - San Francisco

San Francisco, California, 94143, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30329, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Kansas University Medical Center

Kansas City, Kansas, 66160, United States

Location

Louisiana State University

Baton Rouge, Louisiana, 70803, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University Orthopaedics

St Louis, Missouri, 63110, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

Rothman Institute Orthopaedics

Philadelphia, Pennsylvania, 19107, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

University of Utah

Salt Lake City, Utah, 84108, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

Harborview Medical Center

Seattle, Washington, 98104, United States

Location

University of Calgary

Calgary, Alberta, T2N-2T9, Canada

Location

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

University of Toronto Hospital

Toronto, Ontario, M5T 2S8, Canada

Location

McGill University Health Centre

Montral, Quebec, H3H 2L9, Canada

Location

Montreal Neurological Institute

Montreal, Quebec, H3A 2B4, Canada

Location

University of Saskatchewan, Royal University Hospital

Saskatoon, Saskatchewan, S7N 0W8, Canada

Location

Related Publications (5)

• 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.

  PMID: 23962993 BACKGROUND

• 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. 2025 Oct 15. doi: 10.1097/j.pain.0000000000003828. Online ahead of print.

  PMID: 41086299 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. 2025 May 10;16(1):21925682251341263. doi: 10.1177/21925682251341263. Online ahead of print.

  PMID: 40347099 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.

  PMID: 38197642 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.

  PMID: 33357512 DERIVED

MeSH Terms

Interventions

Riluzole

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Benzothiazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Michael Fehlings, MD

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

• Branko Kopjar, MD

  University of Washington

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2010
• First Posted: December 10, 2010
• Study Start: March 1, 2012
• Primary Completion: December 15, 2017
• Study Completion: June 1, 2018
• Last Updated: November 2, 2018

Record last verified: 2018-11

Locations

US (15); CA (6)