Clinical trial NCT01279811: The Canadian Multicentre CSF Monitoring and Biomarker Study
Official title: The Canadian Multicentre CSF Monitoring and Biomarker Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Spinal Cord Injury
Keywords: spinal cord injury, CSF, biomarkers, CSF pressure
Lead sponsor: University of British Columbia
Sponsor class: OTHER
Collaborators: name: Rick Hansen Institute
First posted: 2011-01-19
Enrollment: 86
Sex: ALL
Minimum age (years): 17
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: The purpose of this study is to:

1. Measure the pressure in the spinal fluid surrounding the spinal cord to find out how well the spinal cord is being supplied with blood.
2. Determine how drugs called "vasopressors", which are used to control blood pressure following SCI (spinal cord injury), influence spinal fluid pressure.
3. Characterize the severity of an SCI using the levels of specific proteins found within the spinal fluid.
4. Predict how much neurologic recovery may be regained using the levels of specific proteins within your spinal fluid.
5. Identify proteins within the spinal fluid that will help us learn more about what is happening after SCI and assist us in developing new treatments for SCI.

Detailed description: This research project consists of two complementary yet distinct initiatives:

1. First, we will prospectively evaluate spinal cord perfusion pressure(SCPP)in patients with acute spinal cord injuries, to provide scientifically-based guidelines on the management of blood pressure during the acute injury phase.
2. Second, we will evaluate cerebrospinal fluid(CSF) samples from these patients with the goal of prospectively validating a series of biochemical markers that correlate with injury severity and predict neurologic outcome. Ultimately, our goals are to enhance the neurologic outcome of individuals with spinal cord injuries by improving upon their acute clinical care, and to establish biological surrogates of injury severity that may be used to facilitate clinical trials of novel therapeutic interventions for acute spinal cord injury.

Specific Aims

This multicenter study will enroll patients with acute traumatic cervical and thoracic SCI within 48 hours of their injury. A lumbar intrathecal catheter will be inserted pre-operatively for the measurement of intrathecal pressure (ITP) and the collection of CSF samples. Spinal cord perfusion pressure will be calculated as the difference between mean arterial pressure (MAP) and the ITP. The objectives of this aspect of the study will be to:

* Document the changes in SCPP over the first 5-7 days post-injury (with an intrathecal catheter that is in place for 5 days).
* Determine the effect of different vasopressor agents on SCPP.

Additionally, CSF samples will be obtained from the intrathecal catheter at 8-hour intervals to analyse the expression of the following biochemical markers: including interleukin (IL)-6, IL-8, monocyte chemo-attractant protein (MCP)-1, glial fibrillary acidic protein (GFAP), S100beta, and tau. The objectives of this aspect of the study will be to:

* Evaluate the accuracy of these inflammatory and neuronal markers at classifying the initial severity of paralysis and at predicting the extent of neurologic recovery.
* Characterize the temporal pattern of expression of these proteins to provide a more complete description of the human pathophysiology of SCI.

Eligibility criteria: Inclusion Criteria:

* 17 years of age or older
* Complete (AIS A)or incomplete (AIS B, C) acute SCI involving bony spinal levels between C0 and L1
* Non-penetrating injury
* Able to communicate in English and provide informed consent
* Enrolled within 48 hours after injury and able to provide CSF and blood samples within this period

Exclusion Criteria:

* SCI that involves sensory impairment only (i.e., no impairment in ability to move arms and legs)
* Penetrating spinal cord injury
* Isolated radiculopathy (injury only to the nerve outside of the spinal cord)
* Cauda equina injury (injury to nerve roots at the end of the spinal cord)
* Severe injury to head at the time of the SCI
* Injury to lower back (below the spinal level L1)
* Major injury to legs, arms, pelvis, chest, or abdomen that make it impossible for doctors to tell how severely injured the spinal cord is
* Have a pre-existing neurological disorder such as Parkinson's disease, Alzheimer's disease, Huntington's disease, or multiple sclerosis or amyotrophic lateral sclerosis.
* Pre-existing thromboembolic disease or coagulopathy (disorders related to blood clotting), such as haemophilia or von Willebrand's disease
* Pre-existing and ongoing infection in the body (e.g., pneumonia, urinary tract infection, cellulitis)
* Pre-existing inflammatory or autoimmune disorder such as rheumatoid arthritis, systemic lupus, psoriasis
* Systemic disease that may interfere with safety or evaluation of the condition we're studying (e.g., heart disease, HIV, HTLV-1)
* Any other medical condition that in the investigator's opinion would render the study procedures dangerous or impair ability to receive study therapy
* Pregnancy

Primary outcomes:
measure: Spinal cord perfusion pressure
timeFrame: 5 days
Secondary outcomes:
measure: Levels of specific biochemical markers in the CSF
timeFrame: 5 days
measure: International Standards for Neurological Classification of Spinal Cord Injury (aka ASIA Examination)
timeFrame: 1 year
measure: DN4 and other pain questionnaires
timeFrame: 1 year
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Zuckerberg San Francisco General Hospital (UCSF)
state: California
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: Halifax
country: Canada
facility: QEII Health Sciences Centre
state: Nova Scotia
city: London
country: Canada
facility: London Health Science Centre- Victoria Campus
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Montreal
country: Canada
facility: Hôpital du Sacré-Coeur
state: Quebec
Study officials:
affiliation: University of British Columbia and Vancouver General Hospital
name: Brian K. Kwon, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rosner J, Negraeff M, Belanger LM, Tsang A, Ritchie L, Mac-Thiong JM, Christie S, Wilson JR, Dhall S, Charest-Morin R, Street J, Ailon T, Paquette S, Dea N, Fisher CG, Dvorak MF, Finnerup NB, Kwon BK, Kramer JLK. Characterization of Hyperacute Neuropathic Pain after Spinal Cord Injury: A Prospective Study. J Pain. 2022 Jan;23(1):89-97. doi: 10.1016/j.jpain.2021.06.013. Epub 2021 Jul 21.