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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| SCI patients | Patients with traumatic SCI | ||
| Non-SCI patients (control group) | Non-SCI spine trauma control participants |
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| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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). The primary time points of the serum biomarker levels to be investigated are Day 1, Day 2, Day 3, and Day 4 postinjury (section 5.2). Secondary time points to be explored are Day 5, Day 6, and Day 7 postinjury. These assessment time points also apply to the secondary objectives wherever applicable | 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| 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). | To determine the 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). | 1 Day - 12 months |
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Inclusion Criteria:
Inclusion criteria for non-spinal cord injury spinal trauma control participants:
Exclusion Criteria:
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240 SCI patients with AIS grade A, B, C and D. And 20 non-SCI spine trauma control participants.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Alix Frischknecht | Contact | +41 79 606 41 48 | alix.frischknecht@aofoundation.org | |
| Marije de Jong | Contact | +41 79 529 68 60 | marije.dejong@aofoundation.org |
| Name | Affiliation | Role |
|---|---|---|
| Brian Kwon, MD, PhD, FRCSC | The University of British Columbia | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Medical College of Wisconsin | Recruiting | Milwaukee | Wisconsin | 53226 | United States |
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| ID | Term |
|---|---|
| D013119 | Spinal Cord Injuries |
| ID | Term |
|---|---|
| D013118 | Spinal Cord Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D020196 | Trauma, Nervous System |
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15 mL sample of blood (6 mL for serum, 4 mL for plasma, and 5 mL for RNA isolation)
| Accuracy of serum biomarker levels for predicting other neurologic outcomes at 6 months postinjury |
To determine the accuracy of serum biomarker levels for predicting other neurologic outcomes at 6 months postinjury. Other neurologic outcomes (apart from the one in the primary objective) include:
|
| 6 months |
| 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 | To 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 (ie, motor complete vs motor incomplete, AIS grade conversion, and ≤ vs > 8-point improvement in total motor score). | 6 months |
| 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 | To 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. | 6 months |
| 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. | To 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. | 6 months |
| Investigate the relationship between the accuracy of serum biomarker levels for classification of baseline AIS grade and the perceived reliability of baseline ISNCSCI examination | To investigate the relationship between the accuracy of serum biomarker levels for classification of baseline AIS grade and the perceived reliability of baseline ISNCSCI examination | Baseline |
| Determine the accuracy of serum biomarker levels for predicting neurologic outcomes at 12 months postinjury | To determine the accuracy of serum biomarker levels for predicting neurologic outcomes at 12 months postinjury | 12 months |
| Determine the accuracy of serum biomarker levels for distinguishing acute traumatic SCI from acute spine trauma without neurologic deficit | To determine the accuracy of serum biomarker levels for distinguishing acute traumatic SCI from acute spine trauma without neurologic deficit via the following:
| Baseline |
| Effect of associated trauma on serum biomarker levels | To investigate the effect of associated trauma on serum biomarker levels.
| Baseline |
| Relationship between serum and plasma levels of the biomarkers | To investigate the relationship between serum and plasma levels of the biomarkers. | 12 months |
| Accuracy of ApoE genotype | To determine the accuracy of ApoE genotype, ie, presence vs absence of the ApoE ɛ4 allele, for predicting neurologic outcomes at 6 months and 12 months postinjury, either standalone or in combination with the biomarkers | 6 and 12 months |
| Accuracy of measures of injury severity on baseline MRI | To investigate the accuracy of measures of injury severity on baseline MRI for classifying baseline AIS grade and predicting neurologic outcomes at 6 months and 12 months postinjury, either standalone or in combination with the biomarkers.
| 6 and 12 months |
| Prince of Wales Hospital | Not yet recruiting | Sydney | Randwick NSW | 2031 | Australia |
|
| Cajuru University Hospital | Not yet recruiting | Curitiba | Paraná | 80050-350 | Brazil |
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| Clinica Alemana de Santiago | Recruiting | Santiago | Vitacura | 5951 | Chile |
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| Charité Berlin | Not yet recruiting | Berlin | 10117 | Germany |
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| Sri Balaji Action Medical Institute | Not yet recruiting | New Delhi | 110063 | India |
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| MIddlemore Hospital | Not yet recruiting | Auckland | Otahuhu | 1640 | New Zealand |
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| King's College Hospital | Not yet recruiting | London | SE5 9RS | United Kingdom |
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| D014947 | Wounds and Injuries |