Efficacy of Riluzole in surgical treatment for Cervical Spondylotic Myelopathy (CSM-Protect)

Overview

Status: Enrolling by invitation
Keywords: Cervical Spondylotic Myelopathy , Sodium Glutamate-Drug
IRB Number: 00049505
Specialty: Orthopaedic Surgery, Orthopaedic Surgery
Sub Specialties: Orthopaedic Spine Surgery,

Brief Summary

This is a multi-center, prospective, double-blinded, randomized placebo-controlled clinical trial to evaluate if sodium-glutamate antagonist Riluzole in a dose of 50mg BID 14 days before the surgery and continuing for 28 days after the surgery is superior to placebo in patients with moderate and severe cervical spondylotic myelopathy undergoing surgical decompression.

Detailed Description

CSM (Cervical spondylotic myelopathy) is the most common cause of spinal cord impairment worldwide. The pathophysiology of CSM involves static and dynamic compression of spinal cord which triggers ischemia and secondary cell death by a variety of mechanisms, which prominently include sodium influx and glutamatergic excitotoxicity. While there is emerging evidence from the recently completed AOSpineNA prospective study that surgical decompression is an effective treatment for CSM, it is clear that many patients have substantial residual neurological impairment. Moreover, while surgery is relatively safe, approximately 3% of patients sustain a neurological complication, of which C5 root palsy is the most common adverse outcome. Given this background and compelling evidence from preclinical models of nontraumatic and traumatic spinal cord injury (SCI), there is a strong rationale to consider the potential benefit of adding a neuroprotective drug which targets sodium/glutamate excitoxicity to the treatment of patients with CSM undergoing surgical decompression. Riluzole, a potent sodium/glutamate antagonist has been widely studied in many models of neurotrauma and neurodegenerative disease. This drug is FDA-approved for the treatment of amyotrophic lateral sclerosis, which has some similar clinical features to CSM. Moreover, Riluzole is currently under investigation for traumatic SCI. Given this background, there is a strong rationale to consider studying the potential neurological benefits of Riluzole as an adjunctive treatment to surgical decompression in patients with CSM.

Principal Investigator: Darrel Brodke
Department: Orthopedic Surgery
Co Investigator: Brandon Lawrence
Co Investigator: Erica Bisson

Contact Information

Name:Ashley Woodbury
Phone: 801-339-2710
Email: Ashley.Neese@hsc.utah.edu

Inclusion Criteria

 Signed informed consent
 
 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:
 
o Numb hands
 
o Clumsy hands
 
o Impairment of gait
 
o Bilateral arm paresthesiae
 
o l’Hermitte’s phenomena
 
o Weakness
 
And,
 
(2) one or more of the following signs:
 
o Corticospinal distribution motor deficits
 
o Atrophy of hand intrinsic muscles
 
o Hyperreflexia
 
o Positive Hoffman sign
 
o Upgoing plantar responses
 
o Lower limb spasticity
 
o Broad based, unstable gait
 
And,
 
(3) MRI evidence of cervical spondylotic myelopathy
 
 Scheduled for an elective surgery for cervical spondylotic myelopathy
 
 mJOA score ≥8 and ≤14 at screening
 
 Women must be:
 
o Postmenopausal defined as amenorrhea for at least 2 years.
 
o Surgically sterile, (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy)
 
o Abstinent (at the discretion of the investigator)
 
o Having other congenital or medical condition that prevents subject from becoming pregnant
 
o 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.
 
o 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.
 
-Subject will be using any of the following medications which are classified as CYP1A2 inhibitors or inducers during the course of the drug regimen:
 

  • Ciprofloxacin
  • Enoxacin
  • Fluvoxamine
  • Methoxsalen
  • Mexiletine
  • Oral contraceptives
  • Phenylpropanolamine
  • Thiabendazole
  • Zileuton

Inducers:

  • Montelukast
  • Phenytoin

 
 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