Blood-Based Molecular Clock Biomarkers Predict Acute Ischemic Stroke Onset: A Prospective Observational Study

Condition(s) studied

Study summary

Acute ischemic stroke (AIS) is a major cause of mortality and long-term neurological disability worldwide. The effectiveness of reperfusion therapies such as intravenous thrombolysis and mechanical thrombectomy is highly dependent on the time elapsed since symptom onset. However, in approximately 15-25% of patients, the exact onset time cannot be determined because symptoms begin during sleep (wake-up stroke) or the onset is otherwise unclear. This uncertainty often prevents patients from receiving time-dependent reperfusion treatments.

Currently, imaging-based approaches such as diffusion-weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch are used to estimate the biological stage of ischemia in patients with unknown onset time. However, advanced imaging techniques may not be available in all centers and interpretation may vary.

This study aims to evaluate the diagnostic performance of a multi-biomarker panel representing different biological components of ischemic brain injury, including glial, neuronal, axonal, cellular stress, and vascular responses. Blood samples obtained at admission will be analyzed for glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase L1 (UCH-L1), serum neurofilament light chain (sNfL), phosphatidylethanolamine-binding protein 1 (PEBP1), and matrix metalloproteinase-9 (MMP-9).

The primary objective is to determine whether this biomarker panel can distinguish patients presenting within ≤4.5 hours from those presenting after \>4.5 hours of symptom onset. Biomarker findings will be compared with imaging-based reference methods to explore the feasibility of a blood-based "molecular clock" approach for estimating stroke timing in patients with uncertain onset.

Eligibility

Primary outcome measure(s)

• Diagnostic performance of the multi-biomarker panel in identifying the biological time window of acute ischemic stroke (≤4.5 hours vs >4.5 hours from symptom onset) — At emergency department admission.
  The primary outcome will be the ability of the combined biomarker panel (GFAP, UCH-L1, sNfL, PEBP1, and MMP-9) measured from admission blood samples to discriminate patients presenting within ≤4.5 hours versus \>4.5 hours after symptom onset. Diagnostic performance will be evaluated using receiver operating characteristic (ROC) curve analysis and reported as area under the curve (AUC), sensitivity, specificity, and optimal cut-off values.

Trial sites (1)

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