SpecTRA; An Observational Study of the Verification of Protein Biomarkers in Transient Ischemic Attack.

Study Overview
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Brief Summary
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A multi-protein test using mass spectrometry (MS) for multiplexed protein quantitation is being developed. This test and the accompanying decision-aid software will provide Transient Ischemic Attack (TIA) results rapidly for a fraction of the price of neuroimaging. With guidance provided by this test, Emergency Department (ED) physicians can manage medical imaging questions such as the use of Computed Tomography Angiography (CTA) prior to ED discharge and appropriate (timely) referral to stroke clinics for consultation and follow-up care. The right patients will receive the right treatment, reduce unwarranted imaging risks and costs, and reduce the burden of stroke.

Detailed Description
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This study represents an initial Verification study, in which Mass Spectrometry will be used to quantify a large number of blood proteins previously implicated in ACVS and mimic conditions in patients who are consented and enrolled in the Emergency Department within 24 hrs of symptom onset. 560 patients will be enrolled, and grouped into two cohorts (Cohort 1A: 220; and Cohort 1B: 350). In Cohort 1A, each consented participant provides three blood samples: on arrival, 4-6 hours later, then  24 hours after that, but no later than 32 hours from symptom onset. In cohort 1b, each patient provides only a single blood sample up to 24 hours from symptom onset. A positive diffusion-weighted imaging (DWI) signal on Magnetic Resonance Imaging (MRI) or definite ischemia on Computed tomography (CT) or vascular occlusion on CTA will be used as proof of ischemia to classify the clinical phenotype into three groups (see below). A neurologist will adjudicate all cases according to a study defined adjudication protocol.

Official Title
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Spectrometry for TIA Rapid Assessment (SpecTRA) Project: Study 1 Cohort 1A and 1B-Verification of Protein Biomarkers

Conditions
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TIA

Intervention / Treatment
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* Other: Non-Interventional Study


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 19 and older Suspected TIA (as per <4 NIHSS; or ED physician referral to stroke clinic; English speaking or translator available Competent to provide consent and report symptoms Provides at least one blood sample for the study within 24 hours after symptom onset If three blood samples, then the patient is included in the Verification study 1 Cohort A. If one blood sample, then patient is included in the Verification study 1 Cohort B. Exclusion Criteria: Stroke requiring admission to hospital based on only clinical observations (including CT scan) made before the MRI. Unable to have MRI/CT Subject unable to provide consent. Isolated monocular blindness.

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Mild ACVS-definite<br>Clinical diagnosis of ACVS, and imaging positive (either DWI+ or CT/CTA+). | Other: Non-Interventional Study<br>* This is a non-interventional study. However, several blood samples will be taken which would not be taken as part of standard of care.<br>|
| Mild ACVS-possible<br>Clinical diagnosis of ACVS, and DWI- and/or CTA- | Other: Non-Interventional Study<br>* This is a non-interventional study. However, several blood samples will be taken which would not be taken as part of standard of care.<br>|
| Mimic<br>Clinical diagnosis of mimic and imaging negative. | Other: Non-Interventional Study<br>* This is a non-interventional study. However, several blood samples will be taken which would not be taken as part of standard of care.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Development of a Protein Classifier for the Diagnosis of TIA in the Emergency Department. | 141 proteins measured using multiple reaction monitoring mass spectrometry. Proteins were selected due to previous implication in stroke, TIA, migraine, other conditions that can be confused with ACVS, and other cardiovascular disturbances. | 24 Hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Development of a Clinical Classifier for the Diagnosis of TIA in the Emergency Department. | Clinical score calculated from standard clinical variables using our previously published formula. This score was developed to distinguish ACVS patients (who have had a recent ACVS) from Mimic (patients with symptoms that mimic those of ACVS). | 24 Hours |