Clinical trial NCT06839300: The International Spinal Cord Injury Blood Biomarker Longitudinal Evaluation (I-SCRIBBLE) Study
Official title: The International Spinal Cord Injury Blood Biomarker Longitudinal Evaluation (I-SCRIBBLE) Study
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Spinal Cord Injury
Lead sponsor: AO Foundation, AO Spine
Sponsor class: OTHER
First posted: 2025-02-21
Enrollment: 260
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: 240 SCI patients with AIS grade A, B, C and D. And 20 non-SCI spine trauma control participants.

Brief summary: To determine the accuracy of serum NF-L and GFAP levels (ie the biomarkers) at different time points postinjury for predicting the severity of neurologic impairment at 6 months postinjury as either motor complete (AIS grade A/B) or motor incomplete (AIS grade C/D) a group of patients who suffer traumatic spinal fracture and/or dislocation of the spinal column but without neurologic injury will be enrolled as non-SCI spine trauma control participants.

Detailed description: Patients (≥19 years old) with acute blunt non-penetrating traumatic SCI of AIS grade A, B, C, or D will be enrolled at participating sites. The first blood samples will be drawn within 24 hours of injury (the baseline/enrollment visit); afterwards, blood samples are drawn within each successive 24-hour period postinjury until Day 7, and then at 6 months and 12 months postinjury. Blood samples will be drawn from existing lines (eg, arterial line, central venous catheter \[CVC\] lines, and intravenous \[IV\] line) that are inserted as part of standard of care. If an existing line has been discontinued, blood will be drawn via venipuncture.

At each time point, one 15 mL sample of blood will be drawn, which will be divided into: 6 mL for serum, 4 mL for plasma, and 5 mL for RNA isolation (for transcriptomics). At any of these time points, an additional 1 mL blood sample will also be drawn for DNA extraction (for the purpose of ApoE genotyping). The samples will first be processed and temporarily stored by the sites and then sent to the coordinating center at UBC, Vancouver, Canada, for central storage and analyses. Levels of NF-L and GFAP in serum and plasma will be analyzed on the Quanterix Simoa instrument (Lexington, KY, US) for each time point collected to determine the accuracy of these biomarkers to stratify injury severity and to predict outcome.

To the extent that is possible, a full ISNCSCI examination will be completed at enrollment. A motor-only exam of the upper and lower extremities will be completed at Day 4 and Day 7 postinjury. A full ISNCSCI examination will be repeated at 6- and 12-month visits. The Spinal Cord Independence Measure (SCIM) version III will be completed at 6- and 12-month visits to assess functional recovery.

A group of patients who suffer traumatic spinal fracture and/or dislocation of the spinal column but without neurologic injury will be enrolled as non-SCI spine trauma control participants. For these participants, one 15 mL sample of blood (6 mL for serum, 4 mL for plasma, and 5 mL for RNA isolation) will be drawn within 24 hours of injury (Day 1) and either at discharge or at Day 7 postinjury, whichever comes first. No additional follow-ups (FUs) are required for these control participants.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 19 years
* Blunt (non-penetrating) traumatic SCI
* Baseline neurologic impairment deemed "complete" (AIS grade A) or "incomplete" (AIS grade B, C, or D) based on clinical history/examination and/or diagnostic imaging
* Bony spinal level involvement between C0 and L1, inclusive
* Ability to have initial blood sample drawn within 24 hours of injury
* Treated either surgically or non-surgically
* Ability to provide informed consent according to the IRB/EC defined and approved procedures

Inclusion criteria for non-spinal cord injury spinal trauma control participants:

* Age ≥ 19 years
* Traumatic spinal fracture and/or dislocation between C0 and L1 (inclusive) without SCI
* Treated either surgically or nonsurgically
* Ability to have initial blood sample drawn within 24 hours of injury
* Ability to provide informed consent according to the IRB/EC defined and approved procedures

Exclusion Criteria:

* Penetrating SCI (eg, gunshot, stab)
* Previous SCI
* Isolated spinal injury below L1
* Isolated radiculopathy without fracture
* Isolated cauda equina injury
* Patients with known diagnosis of multiple sclerosis
* Preexisting thromboembolic disease or coagulopathy (disorders related to blood clotting), such as hemophilia or von Willebrand disease
* Patients who in the investigator's opinion will not be compliant with the study procedures and patients who have any other conditions/injuries that in the investigator's opinion would render the study procedures dangerous

Primary outcomes:
measure: Accuracy of serum NF-L and GFAP biomarkers postinjury for predicting the severity of neurologic imapairement at 6 months postinjury as either motor complete or motor incomplete.
timeFrame: 6 months
Secondary outcomes:
measure: Accuracy of serum biomarker levels at different time points postinjury for classifying the baseline injury severity, ie, the AIS grade (A, B, C, and D).
timeFrame: 1 Day - 12 months
measure: Accuracy of serum biomarker levels for predicting other neurologic outcomes at 6 months postinjury
timeFrame: 6 months
measure: Investigate which time point(s) postinjury is/are the most accurate for classifying the baseline AIS grade and predicting neurologic outcomes at 6 months postinjury
timeFrame: 6 months
measure: Investigate whether accuracy of classification and prediction of neurologic outcomes at 6 months postinjury can be enhanced by combining serum NF-L and GFAP levels
timeFrame: 6 months
measure: Investigate whether accuracy of prediction of neurologic outcomes at 6 months postinjury can be enhanced by evaluating the change in serum biomarker levels over time during the first 7 days postinjury.
timeFrame: 6 months
measure: Investigate the relationship between the accuracy of serum biomarker levels for classification of baseline AIS grade and the perceived reliability of baseline ISNCSCI examination
timeFrame: Baseline
measure: Determine the accuracy of serum biomarker levels for predicting neurologic outcomes at 12 months postinjury
timeFrame: 12 months
measure: Determine the accuracy of serum biomarker levels for distinguishing acute traumatic SCI from acute spine trauma without neurologic deficit
timeFrame: Baseline
measure: Effect of associated trauma on serum biomarker levels
timeFrame: Baseline
measure: Relationship between serum and plasma levels of the biomarkers
timeFrame: 12 months
measure: Accuracy of ApoE genotype
timeFrame: 6 and 12 months
measure: Accuracy of measures of injury severity on baseline MRI
timeFrame: 6 and 12 months
Other outcomes:
Locations:
Study officials:
affiliation: The University of British Columbia
name: Brian Kwon, MD, PhD, FRCSC
role: PRINCIPAL_INVESTIGATOR
References: