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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01597518




Registration number
NCT01597518
Ethics application status
Date submitted
10/05/2012
Date registered
14/05/2012
Date last updated
8/07/2020

Titles & IDs
Public title
Riluzole in Spinal Cord Injury Study
Scientific title
A Multi-Center, Randomized, Placebo Controlled, Double-Blinded, Trial of Efficacy and Safety of Riluzole in Acute Spinal Cord Injury
Secondary ID [1] 0 0
SPN-12-001
Universal Trial Number (UTN)
Trial acronym
RISCIS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Spinal Cord Injury 0 0
Condition category
Condition code
Injuries and Accidents 0 0 0 0
Fractures
Injuries and Accidents 0 0 0 0
Other injuries and accidents
Neurological 0 0 0 0
Other neurological disorders
Skin 0 0 0 0
Other skin conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Riluzole
Treatment: Drugs - Placebo

Experimental: Riluzole -

Placebo Comparator: Placebo -


Treatment: Drugs: Riluzole
100mg BID first 24 hours after the injury; 50mg BID 2--14 days following the injury

Treatment: Drugs: Placebo
Placebo 2x in first 24 hours; Placebo 2x day 2--14

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change in ISNCSCI Total Motor Score between 180 days and baseline
Timepoint [1] 0 0
180 Days

Eligibility
Key inclusion criteria
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 ß-human chorionic
gonadotropin (ß-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
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2/Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA
Recruitment hospital [1] 0 0
John Hunter Hospital - Newcastle
Recruitment hospital [2] 0 0
Prince of Wales Hospital - Randwick
Recruitment hospital [3] 0 0
Royal Rehab - Ryde
Recruitment hospital [4] 0 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [5] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 0 0
2310 - Newcastle
Recruitment postcode(s) [2] 0 0
2031 - Randwick
Recruitment postcode(s) [3] 0 0
2112 - Ryde
Recruitment postcode(s) [4] 0 0
2065 - St Leonards
Recruitment postcode(s) [5] 0 0
5000 - Adelaide
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Kansas
Country [6] 0 0
United States of America
State/province [6] 0 0
Kentucky
Country [7] 0 0
United States of America
State/province [7] 0 0
Louisiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Maryland
Country [9] 0 0
United States of America
State/province [9] 0 0
Minnesota
Country [10] 0 0
United States of America
State/province [10] 0 0
Missouri
Country [11] 0 0
United States of America
State/province [11] 0 0
Pennsylvania
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
Utah
Country [14] 0 0
United States of America
State/province [14] 0 0
Virginia
Country [15] 0 0
United States of America
State/province [15] 0 0
Washington
Country [16] 0 0
United States of America
State/province [16] 0 0
Wisconsin
Country [17] 0 0
Canada
State/province [17] 0 0
British Columbia
Country [18] 0 0
Canada
State/province [18] 0 0
Ontario

Funding & Sponsors
Primary sponsor type
Other
Name
AOSpine North America Research Network
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
AO Foundation, AO Spine
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Government body
Name [2] 0 0
United States Department of Defense
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Rick Hansen Institute
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
Christopher Reeve Paralysis Foundation
Address [4] 0 0
Country [4] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT01597518
Trial related presentations / 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.
Fehlings 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.
Wilson 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. Review. Erratum in: CMAJ. 2014 Mar 4;186(4):294.
Grossman 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.
Nagoshi 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. Review.
Nagoshi 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. Review.
Fehlings 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.
Public notes

Contacts
Principal investigator
Name 0 0
Michael Fehlings, MD, PhD
Address 0 0
University Health Network, Toronto, Canada
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications