Spinal Cord InjuryPhase 2/3RISCISNCT01597518
Riluzole in Spinal Cord Injury Study
A Phase 2/3 study testing Riluzole in people with Spinal Cord Injury, run by AOSpine North America Research Network at 29 sites in 3 countries.
Trial summary
The aim of this study is to evaluate efficacy and safety of riluzole in the treatment of patients with acute SCI. The primary objective is to evaluate the superiority of riluzole, at a dose of 2 x 100 mg the first 24 hours followed by 2 x 50 mg for the following 13 days after injury, as compared to placebo, in change… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Spinal Cord Injury
- What is being tested?
- Riluzole
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 193 participants
- Where
- 29 sitesin 3 countries
- Study dates
- Oct 2013to 8 Oct 2020
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age between 18 and 75 years inclusive
- Able to cooperate in the completion of a standardized neurological examination by ISNCSCI standards (includes patients who are on a ventilator)
- Willing and able to comply with the study Protocol
- Signed Informed Consent Document (ICD) by patient, legal representative or witness
- Able to receive the Investigational Drug within 12 hours of injury
- ISNCSCI Impairment Scale Grade "A," "B" or "C" based upon first ISNCSCI evaluation after arrival to the hospital
- Neurological Level of Injury between C4-C8 based upon first ISNCSCI evaluation after arrival to the hospital
- Women of childbearing potential must have a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test or a negative urine pregnancy test
Who cannot join
- Injury arising from penetrating mechanism
- Significant concomitant head injury defined by a Glasgow Coma Scale score < 14 with a clinically significant abnormality on a head CT (head CT required only for patients suspected to have a brain injury at the discretion of the investigator)
- Pre-existent neurologic or mental disorder which would preclude accurate evaluation and follow-up (i.e. Alzheimer's disease, Parkinson's disease, unstable psychiatric disorder with hallucinations and/or delusions or schizophrenia)
- Previous history of spinal cord injury
- Recent history (less than 1 year) of chemical substance dependency or significant psychosocial disturbance that may impact the outcome or study participation, in the opinion of the investigator
- Is a prisoner
Show all 30Show fewer
- Participation in a clinical trial of another Investigational Drug or Investigational Device within the past 30 days
- 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 mg per dL in females at screening visit
- Liver enzymes (ALT/SGPT or AST/SGOT) 3 times the upper limit of normal (ULN) at screening visit
- Active liver disease or clinical jaundice
- Acquired immune deficiency syndrome (AIDS) or AIDS-related complex
- Active malignancy or history of invasive malignancy within the last five years, with the exception of superficial basal cell carcinoma or squamous cell carcinoma of the skin that has been definitely treated. Patients with carcinoma in situ of the uterine cervix treated definitely more than 1 year prior to enrollment may enter the study
- Lactating at screening visit
- Subject is currently using, and will continue to use for the next 14 days any of the following medications which are classified as CYP1A2 inhibitors or inducers*:
- 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
Trial locations and contacts
29 sites in 3 countries.
29 sites in 3 countries
United States20 sites
Emory University
Atlanta, Georgia, 30303
University of Maryland
Baltimore, Maryland, 21201
Louisiana State University
Baton Rouge, Louisiana, 70803
University of Virginia
Charlottesville, Virginia, 22908
University of Missouri
Columbia, Missouri, 65212
Brooke Army Medical Center
Fort Sam Houston, Texas, 78234
UT Health Center
Houston, Texas, 77030
Kansas University Medical Center
Kansas City, Kansas, 66160
University of Louisville
Louisville, Kentucky, 40202
University of Wisconsin - Madison
Madison, Wisconsin, 53706
University of Miami
Miami, Florida, 33136
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
Barrow Neurological Institute
Phoenix, Arizona, 85013
Mayo Clinic
Rochester, Minnesota, 55905
University of Utah
Salt Lake City, Utah, 84112
Santa Clara Valley Medical Center
San Jose, California, 95128
Swedish Hospital
Seattle, Washington, 98122
Washington University
St Louis, Missouri, 63110
Australia5 sites
Royal Adelaide Hospital
Adelaide, South Australia, 5000
John Hunter Hospital
Newcastle, New South Wales, 2310
Prince of Wales Hospital
Randwick, New South Wales, 2031
Royal Rehab
Ryde, New South Wales, 2112
Royal North Shore Hospital
St Leonards, New South Wales, 2065
Canada4 sites
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5
St. Michael's Hospital
Toronto, Ontario, M5R 1C6
University of Toronto Hospital
Toronto, Ontario, M5T 2S8
University of British Columbia
Vancouver, British Columbia, V5Z 1M9
About this study
Official title: A Multi-Center, Randomized, Placebo Controlled, Double-Blinded, Trial of Efficacy and Safety of Riluzole in Acute Spinal Cord Injury
The aim of this study is to evaluate efficacy and safety of riluzole in the treatment of patients with acute SCI. The primary objective is to evaluate the superiority of riluzole, at a dose of 2 x 100 mg the first 24 hours followed by 2 x 50 mg for the following 13 days after injury, as compared to placebo, in change between 180 days and baseline in motor outcomes as measured by International Standards for Neurological Classification of Spinal Cord Injury Examination (ISNCSCI) Motor Score, in patients with acute traumatic SCI, presenting to the hospital less than 12 hours after injury. Secondary objectives are to evaluate the effects of riluzole on overall neurologic recovery, sensory recovery, functional outcomes, quality of life outcomes, health utilities, mortality, and adverse events. The working hypothesis is that the riluzole treated subjects will experience superior motor, sensory, functional, and quality of life outcomes as compared to those receiving placebo, with an acceptable safety profile.
Read the detailed description
At present there are over 1 million people living with Spinal Cord Injury (SCI) in North America alone, with annual costs for the acute treatment and chronic care of these patients totaling four billion dollars USD. The worldwide prevalence of SCI is unknown, with estimates ranging up to 250 million individuals. The incidence of SCI in developed countries has been estimated to be between 10 - 40 cases per million inhabitants. In spite of the immense impact of SCI at a personal and societal level, an effective and safe pharmacologic treatment for SCI, shown to improve neurological and functional outcomes at long-term follow-up, remains absent.
The final degree of neurological tissue destruction that occurs after traumatic SCI is a product of both primary and secondary injury mechanisms. The primary mechanical injury to the cord initiates a subsequent signaling cascade of deleterious down-stream events, known collectively as secondary injury mechanisms. These secondary injury mechanisms include ischemia, interstitial and cellular ionic imbalance, free radical formation, glutamatergic excitotoxicity, lipid peroxidation and generation of arachidonic acid metabolites. Although little can be done from a therapeutic standpoint to correct damage sustained during the primary injury, by mitigating the evolution of secondary injury events there is opportunity to preserve remnant viable neurological tissue and improve neurologic outcomes. There is convincing evidence from the preclinical realm that the pharmacologic agent riluzole attenuates certain aspects of the secondary injury cascade leading to diminished neurological tissue destruction in animal SCI models. Riluzole, a sodium channel blocking benzothiazole anticonvulsant, specifically exerts its neuroprotective effect by helping to maintain neuronal cellular ionic balance and by reducing the release of excitotoxic glutamate in the post-SCI setting. Several preclinical studies in the rodent SCI model have associated administration of riluzole with increased neural tissue preservation at the site of injury, in addition to improved behavioral outcomes, in comparison to administration of placebo or other sodium channel blocking drugs. In the clinical realm, while riluzole has not been studied extensively in the context of SCI, it has been widely used in the treatment of amyotrophic lateral sclerosis (ALS). A 2007 Cochrane review, summarizing the findings of 4 placebo-controlled randomized trials, concluded that at a dose of 100 mg daily, riluzole is safe and improves median survival by 2-3 months in patients with ALS. In regards to adverse events (AEs), riluzole was well tolerated, although treated patients were 2.6 times more likely to experience a three-fold increase in serum alanine transaminase (ALT) as compared to patients treated with placebo. However, this effect was found to be uniformly reversible with cessation of riluzole therapy and was only reported after several months of medication administration. Recently, the clinical safety and pharmacokinetic profile of riluzole have been studied in a multi-center pilot study in the context of traumatic SCI. A total of 36 patients received an oral dose of riluzole 50 mg twice daily for 2 weeks, with treatment initiated within 12 hours of injury for all patients. The 12 hour dosing window, as well as the 2 week duration of therapy, was chosen to match the period of medication administration to the known period of glutamatergic excitotoxicity after SCI (several minutes after injury until 2 weeks after injury). With the final analysis currently undergoing peer review, completion of this study has confirmed the acceptable safety profile of riluzole administration previously documented in the ALS literature, and has established the feasibility of conducting a large-scale efficacy trial investigating this therapy.
At present, there is no specific pharmacological therapy that is given uniformly to all patients with traumatic SCI. As a result, a placebo-controlled comparison group is ethical and justifiable.
The aim of the current trial is to evaluate efficacy and safety of riluzole in the treatment of patients with acute SCI.
The primary objective of the current Phase II/III trial is to evaluate the superiority of riluzole, at a dose of 2 x 100 mg the first 24 hours followed by 2 x 50 mg for the following 13 days after injury, as compared to placebo, in change between 180 days and baseline in motor outcomes as measured by International Standards for Neurological Classification of Spinal Cord Injury Examination (ISNCSCI) Motor Score, in patients with acute traumatic SCI, presenting to the hospital less than 12 hours after injury.
Secondary objectives are to evaluate the effects of riluzole on overall neurologic recovery, sensory recovery, functional outcomes, quality of life outcomes, health utilities, mortality, and adverse events. The working hypothesis is that the riluzole treated subjects will experience superior motor, sensory, functional, and quality of life outcomes as compared to those receiving placebo, with an acceptable safety profile.
- Conditions
- Spinal Cord Injury
- Being tested
- Riluzole, Placebo
- Keywords
- Riluzole, spinal cord injury, treatment
- Medical subject headings
- Spinal Cord Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RiluzoleDrug
100mg BID first 24 hours after the injury; 50mg BID 2--14 days following the injury
PlaceboDrug
Placebo 2x in first 24 hours; Placebo 2x day 2--14
| Study group | Role | What they receive |
|---|---|---|
| Riluzole | Experimental | Not described Receives: Drug: Riluzole |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in ISNCSCI Total Motor Score between 180 days and baseline
Measured: 180 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2012 (estimated)
- Study startOct 2013
- Primary completion8 Oct 2020
- Study completion8 Oct 2020
Why it stopped: Enrollment challenges/ slow enrollment.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for Spinal Cord InjuryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 193 participants (actual)
Sponsor and investigators
- Lead sponsor
- AOSpine North America Research Network
- Sponsor type
- Research network
- Collaborators
- AO Foundation, AO Spine, United States Department of Defense, Rick Hansen Institute, Christopher Reeve Paralysis Foundation
- Responsible party
- Sponsor
- Investigators
- Michael Fehlings, MD, PhD, Principal investigator, University Health Network, Toronto, CanadaBranko Kopjar, MD, PhD, Study director, University of Washington
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01597518
- Sponsor's protocol ID
- SPN-12-001
- Acronym
- RISCIS
- Status last verified
- Apr 2021
- First submitted
- 10 May 2012
- Last updated
- 19 Apr 2021
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Fehlings MG, Wilson JR, Frankowski RF, Toups EG, Aarabi B, Harrop JS, Shaffrey CI, Harkema SJ, Guest JD, Tator CH, Burau KD, Johnson MW, Grossman RG. Riluzole for the treatment of acute traumatic spinal cord injury: rationale for and design of the NACTN Phase I clinical trial. J Neurosurg Spine. 2012 Sep;17(1 Suppl):151-6. doi: 10.3171/2012.4.AOSPINE1259.
PubMed 22985381Fehlings MG, Wilson JR, O'Higgins M. Introduction: Spinal cord injury at the cutting edge of clinical translation: a focus issue collaboration between NACTN and AOSpine North America. J Neurosurg Spine. 2012 Sep;17(1 Suppl):1-3. doi: 10.3171/2012.6.AOSPINE12632. No abstract available.
PubMed 22985363Wilson JR, Forgione N, Fehlings MG. Emerging therapies for acute traumatic spinal cord injury. CMAJ. 2013 Apr 2;185(6):485-92. doi: 10.1503/cmaj.121206. Epub 2012 Dec 10. No abstract available.
PubMed 23228995Grossman RG, Fehlings MG, Frankowski RF, Burau KD, Chow DS, Tator C, Teng A, Toups EG, Harrop JS, Aarabi B, Shaffrey CI, Johnson MM, Harkema SJ, Boakye M, Guest JD, Wilson JR. A prospective, multicenter, phase I matched-comparison group trial of safety, pharmacokinetics, and preliminary efficacy of riluzole in patients with traumatic spinal cord injury. J Neurotrauma. 2014 Feb 1;31(3):239-55. doi: 10.1089/neu.2013.2969. Epub 2013 Oct 11.
PubMed 23859435Nagoshi N, Fehlings MG. Investigational drugs for the treatment of spinal cord injury: review of preclinical studies and evaluation of clinical trials from Phase I to II. Expert Opin Investig Drugs. 2015 May;24(5):645-58. doi: 10.1517/13543784.2015.1009629. Epub 2015 Feb 3.
PubMed 25645889Nagoshi N, Nakashima H, Fehlings MG. Riluzole as a neuroprotective drug for spinal cord injury: from bench to bedside. Molecules. 2015 Apr 29;20(5):7775-89. doi: 10.3390/molecules20057775.
PubMed 25939067Fehlings MG, Nakashima H, Nagoshi N, Chow DS, Grossman RG, Kopjar B. Rationale, design and critical end points for the Riluzole in Acute Spinal Cord Injury Study (RISCIS): a randomized, double-blinded, placebo-controlled parallel multi-center trial. Spinal Cord. 2016 Jan;54(1):8-15. doi: 10.1038/sc.2015.95. Epub 2015 Jun 23.
PubMed 26099215Chow DS, Teng Y, Toups EG, Aarabi B, Harrop JS, Shaffrey CI, Johnson MM, Boakye M, Frankowski RF, Fehlings MG, Grossman RG. Pharmacology of riluzole in acute spinal cord injury. J Neurosurg Spine. 2012 Sep;17(1 Suppl):129-40. doi: 10.3171/2012.5.AOSPINE12112.
PubMed 22985379Wilson JR, Fehlings MG. Riluzole for acute traumatic spinal cord injury: a promising neuroprotective treatment strategy. World Neurosurg. 2014 May-Jun;81(5-6):825-9. doi: 10.1016/j.wneu.2013.01.001. Epub 2013 Jan 4.
PubMed 23295632Carroll AH, Fakhre E, Quinonez A, Tannous O, Mesfin A. An Update on Spinal Cord Injury and Current Management. JBJS Rev. 2024 Oct 24;12(10). doi: 10.2106/JBJS.RVW.24.00124. eCollection 2024 Oct 1.
PubMed 39446982Fehlings MG, Moghaddamjou A, Harrop JS, Stanford R, Ball J, Aarabi B, Freeman BJC, Arnold PM, Guest JD, Kurpad SN, Schuster JM, Nassr A, Schmitt KM, Wilson JR, Brodke DS, Ahmad FU, Yee A, Ray WZ, Brooks NP, Wilson J, Chow DS, Toups EG, Kopjar B. Safety and Efficacy of Riluzole in Acute Spinal Cord Injury Study (RISCIS): A Multi-Center, Randomized, Placebo-Controlled, Double-Blinded Trial. J Neurotrauma. 2023 Sep;40(17-18):1878-1888. doi: 10.1089/neu.2023.0163. Epub 2023 Jul 13.
PubMed 37279301Chow DS, Nguyen A, Park J, Wu L, Toups EG, Harrop JS, Guest JD, Schmitt KM, Aarabi B, Fehlings MG, Boakye M, Grossman RG. Riluzole in Spinal Cord Injury Study (RISCIS)-Pharmacokinetic (PK) Sub-Study: An Analysis of Pharmacokinetics, Pharmacodynamics, and Impact on Axonal Degradation of Riluzole in Patients With Traumatic Cervical Spinal Cord Injury Enrolled in the RISCIS Phase III Randomized Controlled Trial. J Neurotrauma. 2023 Sep;40(17-18):1889-1906. doi: 10.1089/neu.2022.0499.
PubMed 37130044Satkunendrarajah K, Nassiri F, Karadimas SK, Lip A, Yao G, Fehlings MG. Riluzole promotes motor and respiratory recovery associated with enhanced neuronal survival and function following high cervical spinal hemisection. Exp Neurol. 2016 Feb;276:59-71. doi: 10.1016/j.expneurol.2015.09.011. Epub 2015 Sep 21.
PubMed 26394202
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-Center, Randomized, Placebo Controlled, Double-Blinded, Trial of Efficacy and Safety of Riluzole in Acute Spinal Cord Injury
- ClinicalTrials.gov ID
- NCT01597518
- Acronym / sponsor ID
- RISCIS / SPN-12-001
- Conditions
- Spinal Cord Injury
- Keywords
- Riluzole, spinal cord injury, treatment
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Enrollment challenges/ slow enrollment.
- Enrolment
- 193 participants (actual)
- Lead sponsor
- AOSpine North America Research NetworkResearch network
- Collaborators
- AO Foundation, AO Spine, United States Department of Defense, Rick Hansen Institute, Christopher Reeve Paralysis Foundation
- Study start
- Oct 2013 (actual)
- Primary completion
- 8 Oct 2020 (actual)
- Study completion
- 8 Oct 2020 (actual)
- First posted
- 14 May 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of this study is to evaluate efficacy and safety of riluzole in the treatment of patients with acute SCI. The primary objective is to evaluate the superiority of riluzole, at a dose of 2 x 100 mg the first 24 hours followed by 2 x 50 mg for the following 13 days after injury, as compared to placebo, in change between 180 days and baseline in motor outcomes as measured by International Standards for Neurological Classification of Spinal Cord Injury Examination (ISNCSCI) Motor Score, in patients with acute traumatic SCI, presenting to the hospital less than 12 hours after injury. Secondary objectives are to evaluate the effects of riluzole on overall neurologic recovery, sensory recovery, functional outcomes, quality of life outcomes, health utilities, mortality, and adverse events. The working hypothesis is that the riluzole treated subjects will experience superior motor, sensory, functional, and quality of life outcomes as compared to those receiving placebo, with an acceptable safety profile.
Detailed description
At present there are over 1 million people living with Spinal Cord Injury (SCI) in North America alone, with annual costs for the acute treatment and chronic care of these patients totaling four billion dollars USD. The worldwide prevalence of SCI is unknown, with estimates ranging up to 250 million individuals. The incidence of SCI in developed countries has been estimated to be between 10 - 40 cases per million inhabitants. In spite of the immense impact of SCI at a personal and societal level, an effective and safe pharmacologic treatment for SCI, shown to improve neurological and functional outcomes at long-term follow-up, remains absent.
The final degree of neurological tissue destruction that occurs after traumatic SCI is a product of both primary and secondary injury mechanisms. The primary mechanical injury to the cord initiates a subsequent signaling cascade of deleterious down-stream events, known collectively as secondary injury mechanisms. These secondary injury mechanisms include ischemia, interstitial and cellular ionic imbalance, free radical formation, glutamatergic excitotoxicity, lipid peroxidation and generation of arachidonic acid metabolites. Although little can be done from a therapeutic standpoint to correct damage sustained during the primary injury, by mitigating the evolution of secondary injury events there is opportunity to preserve remnant viable neurological tissue and improve neurologic outcomes. There is convincing evidence from the preclinical realm that the pharmacologic agent riluzole attenuates certain aspects of the secondary injury cascade leading to diminished neurological tissue destruction in animal SCI models. Riluzole, a sodium channel blocking benzothiazole anticonvulsant, specifically exerts its neuroprotective effect by helping to maintain neuronal cellular ionic balance and by reducing the release of excitotoxic glutamate in the post-SCI setting. Several preclinical studies in the rodent SCI model have associated administration of riluzole with increased neural tissue preservation at the site of injury, in addition to improved behavioral outcomes, in comparison to administration of placebo or other sodium channel blocking drugs. In the clinical realm, while riluzole has not been studied extensively in the context of SCI, it has been widely used in the treatment of amyotrophic lateral sclerosis (ALS). A 2007 Cochrane review, summarizing the findings of 4 placebo-controlled randomized trials, concluded that at a dose of 100 mg daily, riluzole is safe and improves median survival by 2-3 months in patients with ALS. In regards to adverse events (AEs), riluzole was well tolerated, although treated patients were 2.6 times more likely to experience a three-fold increase in serum alanine transaminase (ALT) as compared to patients treated with placebo. However, this effect was found to be uniformly reversible with cessation of riluzole therapy and was only reported after several months of medication administration. Recently, the clinical safety and pharmacokinetic profile of riluzole have been studied in a multi-center pilot study in the context of traumatic SCI. A total of 36 patients received an oral dose of riluzole 50 mg twice daily for 2 weeks, with treatment initiated within 12 hours of injury for all patients. The 12 hour dosing window, as well as the 2 week duration of therapy, was chosen to match the period of medication administration to the known period of glutamatergic excitotoxicity after SCI (several minutes after injury until 2 weeks after injury). With the final analysis currently undergoing peer review, completion of this study has confirmed the acceptable safety profile of riluzole administration previously documented in the ALS literature, and has established the feasibility of conducting a large-scale efficacy trial investigating this therapy.
At present, there is no specific pharmacological therapy that is given uniformly to all patients with traumatic SCI. As a result, a placebo-controlled comparison group is ethical and justifiable.
The aim of the current trial is to evaluate efficacy and safety of riluzole in the treatment of patients with acute SCI.
The primary objective of the current Phase II/III trial is to evaluate the superiority of riluzole, at a dose of 2 x 100 mg the first 24 hours followed by 2 x 50 mg for the following 13 days after injury, as compared to placebo, in change between 180 days and baseline in motor outcomes as measured by International Standards for Neurological Classification of Spinal Cord Injury Examination (ISNCSCI) Motor Score, in patients with acute traumatic SCI, presenting to the hospital less than 12 hours after injury.
Secondary objectives are to evaluate the effects of riluzole on overall neurologic recovery, sensory recovery, functional outcomes, quality of life outcomes, health utilities, mortality, and adverse events. The working hypothesis is that the riluzole treated subjects will experience superior motor, sensory, functional, and quality of life outcomes as compared to those receiving placebo, with an acceptable safety profile.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Riluzole | Experimental | Drug: Riluzole |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age between 18 and 75 years inclusive
- Able to cooperate in the completion of a standardized neurological examination by ISNCSCI standards (includes patients who are on a ventilator)
- Willing and able to comply with the study Protocol
- Signed Informed Consent Document (ICD) by patient, legal representative or witness
- Able to receive the Investigational Drug within 12 hours of injury
Key exclusion criteria (30 listed)
- Injury arising from penetrating mechanism
- Significant concomitant head injury defined by a Glasgow Coma Scale score < 14 with a clinically significant abnormality on a head CT (head CT required only for patients suspected to have a brain injury at the discretion of the investigator)
- Pre-existent neurologic or mental disorder which would preclude accurate evaluation and follow-up (i.e. Alzheimer's disease, Parkinson's disease, unstable psychiatric disorder with hallucinations and/or delusions or schizophrenia)
- Previous history of spinal cord injury
- Recent history (less than 1 year) of chemical substance dependency or significant psychosocial disturbance that may impact the outcome or study participation, in the opinion of the investigator
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Riluzole100mg BID first 24 hours after the injury; 50mg BID 2--14 days following the injury | Drug | Riluzole |
| PlaceboPlacebo 2x in first 24 hours; Placebo 2x day 2--14 | Drug | Placebo |
Primary outcome
Change in ISNCSCI Total Motor Score between 180 days and baseline
Time frame: 180 Days
Results and safety
The study was stopped early (reason given: Enrollment challenges/ slow enrollment.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2021.
- Background: PubMed 22985381Fehlings MG, Wilson JR, Frankowski RF, Toups EG, Aarabi B, Harrop JS, Shaffrey CI, Harkema SJ, Guest JD, Tator CH, Burau KD, Johnson MW, Grossman RG. Riluzole for the treatment of acute traumatic spinal cord injury: rationale for and design of the NACTN Phase I clinical trial. J Neurosurg Spine. 2012 Sep;17(1 Suppl):151-6. doi: 10.3171/2012.4.AOSPINE1259.
- Background: PubMed 22985363Fehlings MG, Wilson JR, O'Higgins M. Introduction: Spinal cord injury at the cutting edge of clinical translation: a focus issue collaboration between NACTN and AOSpine North America. J Neurosurg Spine. 2012 Sep;17(1 Suppl):1-3. doi: 10.3171/2012.6.AOSPINE12632. No abstract available.
- Background: PubMed 23228995Wilson JR, Forgione N, Fehlings MG. Emerging therapies for acute traumatic spinal cord injury. CMAJ. 2013 Apr 2;185(6):485-92. doi: 10.1503/cmaj.121206. Epub 2012 Dec 10. No abstract available.
- Background: PubMed 23859435Grossman RG, Fehlings MG, Frankowski RF, Burau KD, Chow DS, Tator C, Teng A, Toups EG, Harrop JS, Aarabi B, Shaffrey CI, Johnson MM, Harkema SJ, Boakye M, Guest JD, Wilson JR. A prospective, multicenter, phase I matched-comparison group trial of safety, pharmacokinetics, and preliminary efficacy of riluzole in patients with traumatic spinal cord injury. J Neurotrauma. 2014 Feb 1;31(3):239-55. doi: 10.1089/neu.2013.2969. Epub 2013 Oct 11.
- Background: PubMed 25645889Nagoshi N, Fehlings MG. Investigational drugs for the treatment of spinal cord injury: review of preclinical studies and evaluation of clinical trials from Phase I to II. Expert Opin Investig Drugs. 2015 May;24(5):645-58. doi: 10.1517/13543784.2015.1009629. Epub 2015 Feb 3.
- Background: PubMed 25939067Nagoshi N, Nakashima H, Fehlings MG. Riluzole as a neuroprotective drug for spinal cord injury: from bench to bedside. Molecules. 2015 Apr 29;20(5):7775-89. doi: 10.3390/molecules20057775.
- Background: PubMed 26099215Fehlings MG, Nakashima H, Nagoshi N, Chow DS, Grossman RG, Kopjar B. Rationale, design and critical end points for the Riluzole in Acute Spinal Cord Injury Study (RISCIS): a randomized, double-blinded, placebo-controlled parallel multi-center trial. Spinal Cord. 2016 Jan;54(1):8-15. doi: 10.1038/sc.2015.95. Epub 2015 Jun 23.
- Results publication: PubMed 22985379Chow DS, Teng Y, Toups EG, Aarabi B, Harrop JS, Shaffrey CI, Johnson MM, Boakye M, Frankowski RF, Fehlings MG, Grossman RG. Pharmacology of riluzole in acute spinal cord injury. J Neurosurg Spine. 2012 Sep;17(1 Suppl):129-40. doi: 10.3171/2012.5.AOSPINE12112.
- Results publication: PubMed 23295632Wilson JR, Fehlings MG. Riluzole for acute traumatic spinal cord injury: a promising neuroprotective treatment strategy. World Neurosurg. 2014 May-Jun;81(5-6):825-9. doi: 10.1016/j.wneu.2013.01.001. Epub 2013 Jan 4.
- Derived from this study: PubMed 39446982Carroll AH, Fakhre E, Quinonez A, Tannous O, Mesfin A. An Update on Spinal Cord Injury and Current Management. JBJS Rev. 2024 Oct 24;12(10). doi: 10.2106/JBJS.RVW.24.00124. eCollection 2024 Oct 1.
- Derived from this study: PubMed 37279301Fehlings MG, Moghaddamjou A, Harrop JS, Stanford R, Ball J, Aarabi B, Freeman BJC, Arnold PM, Guest JD, Kurpad SN, Schuster JM, Nassr A, Schmitt KM, Wilson JR, Brodke DS, Ahmad FU, Yee A, Ray WZ, Brooks NP, Wilson J, Chow DS, Toups EG, Kopjar B. Safety and Efficacy of Riluzole in Acute Spinal Cord Injury Study (RISCIS): A Multi-Center, Randomized, Placebo-Controlled, Double-Blinded Trial. J Neurotrauma. 2023 Sep;40(17-18):1878-1888. doi: 10.1089/neu.2023.0163. Epub 2023 Jul 13.
- Derived from this study: PubMed 37130044Chow DS, Nguyen A, Park J, Wu L, Toups EG, Harrop JS, Guest JD, Schmitt KM, Aarabi B, Fehlings MG, Boakye M, Grossman RG. Riluzole in Spinal Cord Injury Study (RISCIS)-Pharmacokinetic (PK) Sub-Study: An Analysis of Pharmacokinetics, Pharmacodynamics, and Impact on Axonal Degradation of Riluzole in Patients With Traumatic Cervical Spinal Cord Injury Enrolled in the RISCIS Phase III Randomized Controlled Trial. J Neurotrauma. 2023 Sep;40(17-18):1889-1906. doi: 10.1089/neu.2022.0499.
- AOSpine North America is a non for profit foundation for excellence in spineLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Fehlings, MD, PhD principal investigator
University Health Network, Toronto, Canada
Branko Kopjar, MD, PhD study director
University of Washington
29 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Riluzole in people with Spinal Cord Injury, run by AOSpine North America Research Network at 29 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 19 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in United States, Australia, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Enrollment challenges/ slow enrollment.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in ISNCSCI Total Motor Score between 180 days and baseline (time frame: 180 Days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01597518, which also lists 13 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Apr 2021.