Riluzole in Spinal Cord Injury Study

NCT01597518 | Terminated Phase 2 DMC

• 1 other identifier: SPN-12-001
• Study Type: interventional
• Target: 193
• Locations: 3 countries
• Sites: 29

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.

Conditions

Spinal Cord Injury

Keywords

Riluzole; spinal cord injury; treatment

Outcome Measures

Primary Outcomes (1)

• Change in ISNCSCI Total Motor Score between 180 days and baseline

  180 Days

Study Arms (2)

Riluzole

EXPERIMENTAL

Drug: Riluzole

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Riluzole DRUG

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

Riluzole

Placebo DRUG

Placebo 2x in first 24 hours; Placebo 2x day 2--14

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AOSpine North America Research Network: lead
• AO Foundation, AO Spine: collaborator
• United States Department of Defense: collaborator
• Rick Hansen Institute: collaborator
• Christopher Reeve Paralysis Foundation: collaborator

Study Sites (29)

Barrow Neurological Institute

Phoenix, Arizona, 85013, United States

Location

Santa Clara Valley Medical Center

San Jose, California, 95128, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Emory University

Atlanta, Georgia, 30303, United States

Location

Kansas University Medical Center

Kansas City, Kansas, 66160, United States

Location

University of Louisville

Louisville, Kentucky, 40202, United States

Location

Louisiana State University

Baton Rouge, Louisiana, 70803, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

University of Missouri

Columbia, Missouri, 65212, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Brooke Army Medical Center

Fort Sam Houston, Texas, 78234, United States

Location

UT Health Center

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

Swedish Hospital

Seattle, Washington, 98122, United States

Location

University of Wisconsin - Madison

Madison, Wisconsin, 53706, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

John Hunter Hospital

Newcastle, New South Wales, 2310, Australia

Location

Prince of Wales Hospital

Randwick, New South Wales, 2031, Australia

Location

Royal Rehab

Ryde, New South Wales, 2112, Australia

Location

Royal North Shore Hospital

St Leonards, New South Wales, 2065, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

University of British Columbia

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

St. Michael's Hospital

Toronto, Ontario, M5R 1C6, Canada

Location

University of Toronto Hospital

Toronto, Ontario, M5T 2S8, Canada

Location

Related Publications (13)

• 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.

  PMID: 22985381 BACKGROUND

• 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. No abstract available.

  PMID: 22985363 BACKGROUND

• 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. No abstract available.

  PMID: 23228995 BACKGROUND

• 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.

  PMID: 23859435 BACKGROUND

• 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.

  PMID: 25645889 BACKGROUND

• 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.

  PMID: 25939067 BACKGROUND

• 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.

  PMID: 26099215 BACKGROUND

• Chow 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.

  PMID: 22985379 RESULT

• Wilson 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.

  PMID: 23295632 RESULT

• Carroll 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.

  PMID: 39446982 DERIVED

• Fehlings 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.

  PMID: 37279301 DERIVED

• Chow 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.

  PMID: 37130044 DERIVED

• Satkunendrarajah 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.

  PMID: 26394202 DERIVED

Related Links

• AOSpine North America is a non for profit foundation for excellence in spine

MeSH Terms

Conditions

Spinal Cord Injuries

Interventions

Riluzole

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Benzothiazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Michael Fehlings, MD, PhD

  University Health Network, Toronto, Canada

  PRINCIPAL INVESTIGATOR

• Branko Kopjar, MD, PhD

  University of Washington

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2012
• First Posted: May 14, 2012
• Study Start: October 1, 2013
• Primary Completion: October 8, 2020
• Study Completion: October 8, 2020
• Last Updated: April 19, 2021

Record last verified: 2021-04

Locations

US (20); AU (5); CA (4)