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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2015 by AOSpine North America Research Network
Sponsor:
Information provided by (Responsible Party):
AOSpine North America Research Network
ClinicalTrials.gov Identifier:
NCT01257828
First received: October 23, 2010
Last updated: May 12, 2015
Last verified: May 2015
  Purpose

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.


Condition Intervention Phase
Cervical Spondylotic Myelopathy
Drug: riluzole
Drug: Placebo medication
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Efficacy of Riluzole in Patients With Cervical Spondylotic Myelopathy Undergoing Surgical Treatment. A Randomized, Double-Blind, Placebo-controlled Multi-Center Study

Resource links provided by NLM:


Further study details as provided by AOSpine North America Research Network:

Primary Outcome Measures:
  • Modified Japanese Orthopedic Association Score (mJOA) [ Time Frame: Before the surgery, 180 days ] [ Designated as safety issue: No ]
    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).


Secondary Outcome Measures:
  • Nurick Score [ Time Frame: Pre-surgical, 180 days ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    The ASIA impairment scale describes a person's functional impairment as a result of their spinal cord injury.


Estimated Enrollment: 270
Study Start Date: December 2011
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Placebo medication and decompressive cervical spine surgery
Drug: Placebo medication
50mg BID orally for 14 days prior to surgery and 28 days after the surgery
Experimental: Riluzole
Riluzole in dose 50mg BID for 14 days prior to surgery and 28 days after the decompressive spine surgery
Drug: riluzole
50mg BID orally for 14 days prior to surgery and 28 days after the surgery
Other Name: Rilutek

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01257828

  Show 19 Study Locations
Sponsors and Collaborators
AOSpine North America Research Network
Investigators
Principal Investigator: Michael Fehlings, MD University Health Network, Toronto
Study Director: Branko Kopjar, MD University of Washington
  More Information

Publications:
Responsible Party: AOSpine North America Research Network
ClinicalTrials.gov Identifier: NCT01257828     History of Changes
Other Study ID Numbers: SPN-10-001
Study First Received: October 23, 2010
Last Updated: May 12, 2015
Health Authority: United States: Institutional Review Board
Canada: Health Canada

Additional relevant MeSH terms:
Bone Marrow Diseases
Hematologic Diseases
Riluzole
Anticonvulsants
Central Nervous System Agents
Excitatory Amino Acid Agents
Excitatory Amino Acid Antagonists
Molecular Mechanisms of Pharmacological Action
Neuroprotective Agents
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 28, 2015