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

• ClinicalTrials.gov Identifier: NCT01257828
• Recruitment Status: Completed
• First Posted: December 10, 2010
• Last Update Posted: November 2, 2018
• Sponsor: AOSpine North America Research Network
• Information provided by (Responsible Party): AOSpine North America Research Network

Tracking Information

• First Submitted Date: October 23, 2010
• First Posted Date: December 10, 2010
• Last Update Posted Date: November 2, 2018
• Actual Study Start Date: March 2012
• Actual Primary Completion Date: December 15, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 8, 2010)

Modified Japanese Orthopedic Association Score (mJOA) [ Time Frame: Before the surgery, 180 days ]

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).

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 1, 2013)

• Nurick Score [ Time Frame: Pre-surgical, 180 days ]
  Nurick score is a simple measure of neurological dysfunction and ranges from 0 (best) to 6 (worst).
• SF-36v2.0 [ Time Frame: Before the surgery, 180 days ]
  The SF36v2.0 is a health-related quality of life instrument that evaluates health status accross eight health dimensions.
• Neck Disability Index (NDI) [ Time Frame: Before the surgery, 180 days ]
  The NDI evaluates patient self-reported functional outcomes related to neck conditions. The NDI score ranges from 0 (best) to 100 (worst).
• Cervical Pain Numeric Rating Scale [ Time Frame: Before the surgery, 180 days ]
  Simple numeric rating scale with choises of answers from 0 (no pain) to 10 (worst imaginable pain)
• EQ-5D [ Time Frame: Before the surgery, 180 days ]
  EQ-5D™ 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.
• American Spinal Injury Association Score (ASIA) [ Time Frame: Before the surgery, 180 days ]
  The ASIA impairment scale describes a person's functional impairment as a result of their spinal cord injury.

Original Secondary Outcome Measures (submitted: December 8, 2010)

• Nurick Score [ Time Frame: Pre-surgical, 180 days ]
  Nurick score is a simple measure of neurological dysfunction and ranges from 0 (best) to 6 (worst).
• SF-36v2.0 [ Time Frame: Before the surgery, 180 days ]
  The SF36v2.0 is a health-related quality of life instrument that evaluates health status accross eight health dimensions.
• Neck Disability Index (NDI) [ Time Frame: Before the surgery, 180 days ]
  The NDI evaluates patient self-reported functional outcomes related to neck conditions. The NDI score ranges from 0 (best) to 100 (worst).
• Cervical Pain Numeric Rating Scale [ Time Frame: Before the surgery, 180 days ]
  Simple numeric rating scale with choises of answers from 0 (no pain) to 10 (worst imaginable pain)
• EQ-5D [ Time Frame: Before the surgery, 180 days ]
  EQ-5D™ 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.
• sia American Spinal Injury Association Score (ASIA) [ Time Frame: Before the surgery, 180 days ]
  The ASIA impairment scale describes a person's functional impairment as a result of their spinal cord injury.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy of Riluzole in Surgical Treatment for Cervical Spondylotic Myelopathy (CSM-Protect)
• Official Title: Efficacy of Riluzole in Patients With Cervical Spondylotic Myelopathy Undergoing Surgical Treatment. A Randomized, Double-Blind, Placebo-controlled Multi-Center Study
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Cervical Spondylotic Myelopathy

Intervention

• Drug: riluzole
  50mg BID orally for 14 days prior to surgery and 28 days after the surgery
  Other Name: Rilutek
• Drug: Placebo medication
  50mg BID orally for 14 days prior to surgery and 28 days after the surgery

Study Arms

• Placebo Comparator: Placebo
  Placebo medication and decompressive cervical spine surgery
  Intervention: Drug: Placebo medication
• Experimental: Riluzole
  Riluzole in dose 50mg BID for 14 days prior to surgery and 28 days after the decompressive spine surgery
  Intervention: Drug: riluzole

Publications *

• 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. Review.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 8, 2010): 270
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: June 1, 2018
• Actual Primary Completion Date: December 15, 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Age between 18 and 80 years

• Diagnosis of symptomatic cervical spondylotic myelopathy defined as a combination of:

  1. one or more of the following symptoms:

     • Numb hands
     • Clumsy hands
     • Impairment of gait
     • Bilateral arm paresthesiae
     • l'Hermitte's phenomena
     • Weakness And,

  2. one or more of the following signs:

     • Corticospinal distribution motor deficits
     • Atrophy of hand intrinsic muscles
     • Hyperreflexia
     • Positive Hoffman sign
     • Upgoing plantar responses
     • Lower limb spasticity
     • Broad based, unstable gait And,
  3. 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:

  • Postmenopausal defined as amenorrhea for at least 2 years.
  • Surgically sterile, (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy)
  • Abstinent (at the discretion of the investigator)
  • Having other congenital or medical condition that prevents subject from becoming pregnant
  • If sexually active, be practicing an effective method of birth control such as hormonal prescription oral contraceptives, progesterone implants or injections, intrauterine device (IUD), or male partner with a vasectomy. A double-barrier method such as condoms, diaphragms or cervical caps with spermicidal foam, cream or gel may be used as a birth control method.
  • Women of childbearing potential must have a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test or a negative urine pregnancy test at screening before the first dose of study drug is received.

Exclusion Criteria:

• 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
• Phenylpropanolamine
• Thiabendazole
• Zileuton

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, United States

Administrative Information

• NCT Number: NCT01257828
• Other Study ID Numbers: SPN-10-001
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: AOSpine North America Research Network
• Original Responsible Party: Nancy Holmes, AO Spine North America
• Current Study Sponsor: AOSpine North America Research Network
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Michael Fehlings, MD; University Health Network, Toronto
• Study Director: Branko Kopjar, MD; University of Washington

• PRS Account: AOSpine North America Research Network
• Verification Date: November 2018