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Trial record 10 of 16 for:    SCI | Spinal Cord Injuries | ( Map: Minnesota, United States )

Riluzole in Spinal Cord Injury Study (RISCIS)

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ClinicalTrials.gov Identifier: NCT01597518
Recruitment Status : Recruiting
First Posted : May 14, 2012
Last Update Posted : September 6, 2019
Sponsor:
Collaborators:
AOSpine International
United States Department of Defense
Rick Hansen Institute
Christopher Reeve Paralysis Foundation
Information provided by (Responsible Party):
AOSpine North America Research Network

Tracking Information
First Submitted Date  ICMJE May 10, 2012
First Posted Date  ICMJE May 14, 2012
Last Update Posted Date September 6, 2019
Actual Study Start Date  ICMJE October 2013
Estimated Primary Completion Date December 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 29, 2012)
Change in ISNCSCI Total Motor Score between 180 days and baseline [ Time Frame: 180 Days ]
Original Primary Outcome Measures  ICMJE
 (submitted: May 11, 2012)
Change in ASIA Total Motor Score between pre-treatment and 6 months [ Time Frame: 6 months ]
Change History Complete list of historical versions of study NCT01597518 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Riluzole in Spinal Cord Injury Study
Official Title  ICMJE A Multi-Center, Randomized, Placebo Controlled, Double-Blinded, Trial of Efficacy and Safety of Riluzole in Acute Spinal Cord Injury
Brief 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 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Spinal Cord Injury
Intervention  ICMJE
  • Drug: Riluzole
    100mg BID first 24 hours after the injury; 50mg BID 2--14 days following the injury
  • Drug: Placebo
    Placebo 2x in first 24 hours; Placebo 2x day 2--14
Study Arms  ICMJE
  • Experimental: Riluzole
    Intervention: Drug: Riluzole
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 21, 2012)
351
Original Estimated Enrollment  ICMJE
 (submitted: May 11, 2012)
252
Estimated Study Completion Date  ICMJE May 2025
Estimated Primary Completion Date December 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

INCLUSION:

  • 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

EXCLUSION:

  • 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
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States,   Australia,   Canada,   New Zealand
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01597518
Other Study ID Numbers  ICMJE SPN-12-001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party AOSpine North America Research Network
Study Sponsor  ICMJE AOSpine North America Research Network
Collaborators  ICMJE
  • AOSpine International
  • United States Department of Defense
  • Rick Hansen Institute
  • Christopher Reeve Paralysis Foundation
Investigators  ICMJE
Principal Investigator: Michael Fehlings, MD, PhD University Health Network, Toronto, Canada
Study Director: Branko Kopjar, MD, PhD University of Washington
PRS Account AOSpine North America Research Network
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP