The Canadian Multicentre CSF Monitoring and Biomarker Study

Spinal Cord Injury Clinical Trial

— CAMPER  

Official title:

The Canadian Multicentre CSF Monitoring and Biomarker Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01279811
• Other study ID #: H10-01091
• Status: Completed
• Phase: N/A
• Start date: January 2012
• Est. completion date: September 30, 2020

Study information

• Verified date: November 2020
• Source: University of British Columbia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 86
• Est. completion date: September 30, 2020
• Est. primary completion date: September 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 17 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Spinal Cord Injuries
• Spinal Cord Injury

Intervention

Other:
• Crossover of vasopressors
To evaluate the effect of different vasopressor agents on SCPP, a "crossover" intervention will be conducted on patients requiring either NORepinephrine or DOPamine post-operatively, once daily for 5 days while the catheter is in place. A subject on NORepinephrine will be switched over to DOPamine for 1 hr, and then switched back to NORepinephrine. Likewise, a subject on DOPamine will be switched over to NORepinephrine for 1 hr, and then switched back to DOPamine. Subjects on both vasopressors will have DOPamine stopped for 1 hr and NORepinephrine titrated up to maintain the same MAP for 1 hr, and then brought back to the original levels of both vasopressors. On the following day, the reverse will be carried out, with a stoppage of the NORepinephrine and maintenance solely on DOPamine.

Locations

Country	Name	City	State
Canada	QEII Health Sciences Centre	Halifax	Nova Scotia
Canada	London Health Science Centre- Victoria Campus	London	Ontario
Canada	Hôpital du Sacré-Coeur	Montreal	Quebec
Canada	St. Michael's Hospital	Toronto	Ontario
Canada	Vancouver General Hospital	Vancouver	British Columbia
United States	Zuckerberg San Francisco General Hospital (UCSF)	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
University of British Columbia	Rick Hansen Institute

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Spinal cord perfusion pressure	SCPP will be calculated as the difference between the MAP and ITP. The ITP and MAP will be recorded over 5 days(5-7 days post-injury) while the lumbar intrathecal catheter is in place.	5 days
Secondary	Levels of specific biochemical markers in the CSF	CSF samples will be obtained from the intrathecal catheter at 8-hour intervals, three times daily for 5 days. These samples will be evaluated will the goal of prospectively validating a series of biochemical markers that correlate with injury severity and predict neurologic outcome.	5 days
Secondary	International Standards for Neurological Classification of Spinal Cord Injury (aka ASIA Examination)	For the purposes of ensuring that neurologic deterioration is not occurring while the lumbar intrathecal catheter is in place, an ASIA assessment will be performed daily while the intrathecal catheter is inserted. For the purpose of documenting neurologic recovery over time, the ASIA examination will also be performed at 3, 6, and 12 months post-injury.	1 year
Secondary	DN4 and other pain questionnaires	It is currently believed that the development of neuropathic pain is closely related to neuroinflammation after SCI. In an effort to determine if we could establish etiologic cytokines, we will administer the DN4 and other pain questionnaires to characterize and quantify neuropathic pain. These questionnaires will be administered at screening, days 1-5 post-insertion of the lumbar intrathecal catheter, 3 months, 6 months and 1 year post-injury.	1 year