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

Study Overview
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Brief Summary
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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.

Official Title
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Efficacy of Riluzole in Patients With Cervical Spondylotic Myelopathy Undergoing Surgical Treatment. A Randomized, Double-Blind, Placebo-controlled Multi-Center Study

Conditions
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Cervical Spondylotic Myelopathy

Intervention / Treatment
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* Drug: riluzole
* Drug: Placebo medication


Participation Criteria
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Eligibility Criteria
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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: 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 Lower limb spasticity Broad based, unstable gait And, 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo medication and decompressive cervical spine surgery | Drug: Placebo medication<br>* 50mg BID orally for 14 days prior to surgery and 28 days after the surgery<br>|
| Experimental: Riluzole<br>Riluzole in dose 50mg BID for 14 days prior to surgery and 28 days after the decompressive spine surgery | Drug: riluzole<br>* 50mg BID orally for 14 days prior to surgery and 28 days after the surgery<br>* Other names: Rilutek;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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. | 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-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. | 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 |