NCT05518305

Platelet Expression of FcγRIIa and Arterial Hemodynamics to Predict Recurrent Stroke in Intracranial Atherosclerosis

Platelet Expression of FcγRIIa and Arterial Hemodynamics to Predict Recurrent Stroke in Intracranial Atherosclerosi

• Status: Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 250 (estimated)
• Sponsor: University of California, Los Angeles · Academic / Other
• Sex: All
• Age: 30 Years
• Healthy volunteers: Accepted

Summary

An observational study to determine if individuals with increased platelet FcyRIIa will have a higher risk of ischemic events.

Detailed description

Recurrent ischemic stroke due to intracranial atherosclerotic disease (ICAD) is extremely common despite treatment with anti-platelet medications. Heterogeneity of the arterial architecture and associated blood flow changes in ICAD-related stenoses result in different patterns of wall shear stress (WSS) from one individual to the next. Such wall shear stress can be readily quantified with computational fluid dynamics (CFD) from noninvasive CT angiography (CTA), routinely acquired in patients with minor stroke or transient ischemic attack (TIA) due to ICAD. These shear stress changes in blood flow promote platelet aggregation and thereby alter the response to anti-platelet therapy. Additionally, greater platelet FcγRIIa expression increases platelet reactivity and promotes thrombosis when platelets are exposed to increased shear stress. In the coronary circulation, greater platelet expression of FcγRIIa identifies patients at greater risk of recurrent cardiovascular events, including stroke. Numerous mechanisms have been invoked in the recurrence of ischemia in ICAD, yet focused research on the pathophysiology of shear stress and platelet activation has not been evaluated to explain the high rate of imaging evidence and clinical strokes following minor stroke or TIA due to ICAD. Given the shared pathology of coronary artery disease and ICAD, the data suggest that individual differences in CFD-derived WSS and platelet FcγRIIa expression may inform a precision medicine strategy to prevent recurrent stroke. The investigators developed a novel approach to validate CTA CFD values of WSS in stenoses in ICAD with precision 3D cerebrovascular models, including data from the landmark SAMMPRIS trial. In other collaborations, The investigators have separately studied the potential impact of elevated WSS on stroke recurrence in ICAD and conducted an observational multicenter study on mechanisms of recurrent stroke in ICAD. The investigators and others have demonstrated that greater platelet FcγRIIa expression increases the activation of platelets in response to agonists and shear stress. These synergies now enable us to investigate how the interaction of anti-platelet therapies with individual platelet expression of FcγRIIa and WSS calculated from patient-specific CTA CFD may explain recurrent ischemia after minor stroke or TIA due to ICAD. The investigators hypothesize that the incidence of recurrent silent ischemia on MRI and clinical strokes by 1 year after minor stroke or TIA due to ICAD will be predicted by quantifying individual risk determined by platelet FcγRIIa expression and focal elevations in WSS due to stenosis.

Conditions

• Stroke
• TIA
• Ischemic Stroke
• Ischemic

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	Medical Imaging	magnetic resonance imaging

Timeline

• Start date: 2022-09-30
• Primary completion: 2027-09-30
• Completion: 2027-09-30
• First posted: 2022-08-26
• Last updated: 2025-04-16

Locations

1 site across 1 country: United States