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

Phase 3
Completed
Conditions
Cervical Spondylotic Myelopathy
Interventions
Drug: Placebo medication
Registration Number
NCT01257828
Lead Sponsor
AOSpine North America Research Network
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 available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
270
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlacebo medicationPlacebo medication and decompressive cervical spine surgery
RiluzoleriluzoleRiluzole in dose 50mg BID for 14 days prior to surgery and 28 days after the decompressive spine surgery
Primary Outcome Measures
NameTimeMethod
Modified Japanese Orthopedic Association Score (mJOA)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).

Secondary Outcome Measures
NameTimeMethod
Nurick ScorePre-surgical, 180 days

Nurick score is a simple measure of neurological dysfunction and ranges from 0 (best) to 6 (worst).

SF-36v2.0Before 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)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 ScaleBefore the surgery, 180 days

Simple numeric rating scale with choises of answers from 0 (no pain) to 10 (worst imaginable pain)

EQ-5DBefore 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)Before the surgery, 180 days

The ASIA impairment scale describes a person's functional impairment as a result of their spinal cord injury.

Trial Locations

Locations (21)

Barrow Neurological Institute

🇺🇸

Phoenix, Arizona, United States

Louisiana State University

🇺🇸

Baton Rouge, Louisiana, United States

Mayo Clinic

🇺🇸

Rochester, Minnesota, United States

University of Virginia

🇺🇸

Charlottesville, Virginia, United States

University of Saskatchewan, Royal University Hospital

🇨🇦

Saskatoon, Saskatchewan, Canada

University of Calgary

🇨🇦

Calgary, Alberta, Canada

McGill University Health Centre

🇨🇦

Montral, Quebec, Canada

Montreal Neurological Institute

🇨🇦

Montreal, Quebec, Canada

UC Davis Spine Center

🇺🇸

Sacramento, California, United States

St. Michael's Hospital

🇨🇦

Toronto, Ontario, Canada

Emory University School of Medicine

🇺🇸

Atlanta, Georgia, United States

The Ohio State University

🇺🇸

Columbus, Ohio, United States

Rush University Medical Center

🇺🇸

Chicago, Illinois, United States

Kansas University Medical Center

🇺🇸

Kansas City, Kansas, United States

University of California - San Francisco

🇺🇸

San Francisco, California, United States

Harborview Medical Center

🇺🇸

Seattle, Washington, United States

Rothman Institute Orthopaedics

🇺🇸

Philadelphia, Pennsylvania, United States

Washington University Orthopaedics

🇺🇸

Saint Louis, Missouri, United States

University of Utah

🇺🇸

Salt Lake City, Utah, United States

University of Toronto Hospital

🇨🇦

Toronto, Ontario, Canada

Thomas Jefferson University

🇺🇸

Philadelphia, Pennsylvania, United States

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