Purpose of the Study: The primary objective of this study is to evaluate whether the sodium-glutamate antagonist riluzole in a dose of 50mg BID 14 days prior to the surgery and 28 days following the surgery is superior to placebo in achieving better neurological outcomes in patients undergoing surgical decompression for moderate or severe cervical spondylotic myelopathy. The study will also evaluate differences between the investigational and the control group as measured by pain, functional and quality of life outcomes, health utilities, and adverse events.
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 the spinal cord which triggers ischemia and secondary cell death by a variety of mechanisms, including sodium influx and glutamatergic excitotoxicity. While the recently completed AOSpineNA prospective study suggests 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 non-traumatic 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 excitotoxicity 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.
Eligibility Criteria: Adults ages 18 and 80 years diagnosed with symptomatic cervical spondylotic myelopathy and able to provide signed informed consent. Participants must be scheduled for an elective surgery for cervical spondylotic myelopathy and have a mJOA score between 8 and 14 at screening. Patients with previous CMS surgery, hypersensitivity to riluzole or its components, cervical trauma, symptomatic lumbar stenosis, or are on CYP1A2 inhibitors or inducers are not eligible. Women who are pregnant or may become pregnant, or are breastfeeding are not eligible. Other criteria and exclusions apply.
Full eligibility criteria:
Adults ages 18 and 80 years diagnosed with symptomatic cervical spondylotic myelopathy and able to provide signed informed consent. Diagnosis of symptomatic cervical spondylotic myelopathy is 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
- Condurent with one or more of the following signs:
- Corticospinal distribution motor deficits
- Atrophy of hand intrinsic muscles
- Positive Hoffman sign
- Upgoing plantar responses
- Lower limb spasticity
- Broad based, unstable gait
- MRI evidence of cervical spondylotic myelopathy
Participants must be scheduled for an elective surgery for cervical spondylotic myelopathy and have a mJOA score ≥8 and ≤14 at screening.
Female participants 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
- Or 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.
- 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 mg/dl in males or > 1.1 mg/dl in females at screening visit.
- Liver enzymes (ALT or AST) 3x higher than normal values at screening visit.
- Subjects using any of the following medications which are classified as CYP1A2 inhibitors or inducers during the course of the drug regimen:
- Oral contraceptives
*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 (<3 years) of chemical substance dependency or significant psychosocial disturbance that may impact the outcome or study participation.
- Women breastfeeding at screening visit and who plan to continue breastfeeding 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 Status: Open to Accrual
Principal Investigator: H. Francis Farhadi, MD, PhD
Contact: Amy Minnema, Clinical Research Coordinator, at 614-685-9827 or firstname.lastname@example.org
Funding/Study Sponsor: AOSpine North America