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

Cervical Spondylotic Myelopathy Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01257828
• Other study ID #: SPN-10-001
• Status: Completed
• Phase: Phase 3
• Start date: March 2012
• Est. completion date: June 1, 2018

Study information

• Verified date: November 2018
• Source: AOSpine North America Research Network
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 270
• Est. completion date: June 1, 2018
• Est. primary completion date: December 15, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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 ß-human chorionic gonadotropin (ß-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

Related Conditions & MeSH terms

• Bone Marrow Diseases
• Cervical Spondylotic Myelopathy
• Spinal Cord Diseases

Intervention

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

Locations

Country	Name	City	State
Canada	University of Calgary	Calgary	Alberta
Canada	McGill University Health Centre	Montral	Quebec
Canada	Montreal Neurological Institute	Montreal	Quebec
Canada	University of Saskatchewan, Royal University Hospital	Saskatoon	Saskatchewan
Canada	St. Michael's Hospital	Toronto	Ontario
Canada	University of Toronto Hospital	Toronto	Ontario
United States	Emory University School of Medicine	Atlanta	Georgia
United States	Louisiana State University	Baton Rouge	Louisiana
United States	University of Virginia	Charlottesville	Virginia
United States	Rush University Medical Center	Chicago	Illinois
United States	The Ohio State University	Columbus	Ohio
United States	Kansas University Medical Center	Kansas City	Kansas
United States	Rothman Institute Orthopaedics	Philadelphia	Pennsylvania
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Barrow Neurological Institute	Phoenix	Arizona
United States	Mayo Clinic	Rochester	Minnesota
United States	UC Davis Spine Center	Sacramento	California
United States	Washington University Orthopaedics	Saint Louis	Missouri
United States	University of Utah	Salt Lake City	Utah
United States	University of California - San Francisco	San Francisco	California
United States	Harborview Medical Center	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
AOSpine North America Research Network

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Nurick Score	Nurick score is a simple measure of neurological dysfunction and ranges from 0 (best) to 6 (worst).	Pre-surgical, 180 days
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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