Prevalence and Etiologies of Intracranial Stenosis in Patients With Antiphospholipid Syndrome

NCT05583305 | Enrolling By Invitation

• 1 other identifier: CREC 2022.352
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Antiphospholipid syndrome (APS) is an important cause of young stroke which could result in major disability. Cohort studies suggested that 17% of young ischemic stroke were accountable by APS (1). Although warfarin has been the mainstay of treatment in APS for the past decades, recurrent thromboembolism occurred up to 10% of warfarinized patients with APS (2, 3). These observations call for an in-depth understanding of disease mechanisms secondary to antiphospholipid antibodies (aPL). Contrary to traditional understanding, recent evidence suggested mechanisms of cerebrovascular ischemia in APS are far more complex than hypercoagulability alone. In the proposed cross-sectional study, we aim to determine the prevalence of intracranial stenosis, and to explore the correlations between the neuroimaging findings and the immunological as well as clinical features in patients with APS. In the proposed cross-sectional study, we aim to determine the prevalence of intracranial stenosis, and to explore the correlations between the neuroimaging findings and the immunological as well as clinical features in patients with APS.

Conditions

Stenosis; Antiphospholipid Syndrome; Intracranial Stenosis

Outcome Measures

Primary Outcomes (1)

• Radiological evidence of intracranial arterial stenosis

  Defined as the presence of \>50% stenosis of any intracranial arteries (ICA, MCA, anterior cerebral arteries, posterior cerebral arteries, basilar artery, or vertebral arteries) or presence of arterial plaques in vessel wall imaging.

  31／01／2026

Secondary Outcomes (1)

• Other radiological outcomes

  31／01／2026

Study Arms (2)

Patients diagnosed with APS

Investigators shall recruit patients with the following criteria: 1. Diagnosed with APS who fulfilled the modified Sapporo criteria: 1. at least one clinical criterion (vascular thrombosis or pregnancy morbidity); and 2. laboratory criteria (aPL positivity twice, 12 weeks apart): i. Lupus anticoagulant positivity requires screening, mixing, and confirmation test as per International Society of Thrombosis and Hemostasis guidelines (11). ii. Anticardiolipin antibodies positivity requires a medium to high titer IgG and/or IgM level by ELISA assays. iii. Anti-β2 glycoprotein antibodies positivity requires a \>99th titer IgG and/or IgM level by ELISA assays. 2. Patients age ≥18 years 3. Patients who are able to provide an informed consent to study procedures

Diagnostic Test: Imaging assessment; Diagnostic Test: Neurosonology assessment; Diagnostic Test: Blood Test

Controls

From the ongoing prospective Brain Health Longitudinal study which contained stroke- and dementia free participants (CREC Ref. No: 2018.148), investigators shall identify age- and gender-matched individuals without aPLs as controls

Diagnostic Test: Imaging assessment; Diagnostic Test: Neurosonology assessment; Diagnostic Test: Blood Test

Interventions

Imaging assessment DIAGNOSTIC_TEST

Investigators shall perform cranial MRI examinations. The scanning protocol will employ an MRI scan protocol with T1-weighted, T2-weighted, FLAIR, susceptibility weighted imaging, diffusion weighted imaging, and time-of-flight magnetic resonance angiography (MRA) sequences. In addition, high-resolution magnetic resonance vessel wall imaging (HRMRI) allows assessment of the vessel wall using specific the SPACE sequence and the MATCH sequence. Assessors of the HRMRI images shall be blinded to the group allocation and clinical information.

Controls; Patients diagnosed with APS

Neurosonology assessment DIAGNOSTIC_TEST

Investigators shall perform carotid duplex ultrasonography (CD) assessment, focusing on the peak systolic (PSV) and end diastolic velocity (EDV) of bilateral extracranial internal carotid arteries (ICA) Brightness mode imaging shall gauge the intimal thickness and plaque characteristics (if any) of bilateral ICAs.

Controls; Patients diagnosed with APS

Blood Test DIAGNOSTIC_TEST

Nine milliliters of EDTA blood will be drawn during the research clinic visit for evaluation of the degree of neurovascular inflammation. Serum plasminogen activator inhibitor-1 (PAI-1) and high-sensitive C-reactive protein (hsCRP) are markers of vascular inflammation, atherosclerosis, and thrombotic risk. Serum neurofilament light chain (NfL) is a biomarker for neuroaxonal injury that correlates with small vessel disease.

Controls; Patients diagnosed with APS

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Adults with or without APS

You may qualify if:

• Patients diagnosed with APS who fulfilled the modified Sapporo criteria:
• at least one clinical criterion (vascular thrombosis or pregnancy morbidity); and
• laboratory criteria (aPL positivity twice, 12 weeks apart):
• i. Lupus anticoagulant positivity requires screening, mixing, and confirmation test as per International Society of Thrombosis and Hemostasis guidelines (11). ii. Anticardiolipin antibodies positivity requires a medium to high titer IgG and/or IgM level by ELISA assays. iii. Anti-β2 glycoprotein antibodies positivity requires a \>99th titer IgG and/or IgM level by ELISA assays.
• Patients age ≥18 years
• Patients who are able to provide an informed consent to study procedures

You may not qualify if:

• Patient with established neurological disease, such as stroke, cerebral venous thrombosis, vasculitis of the central nervous system, cerebral lupus, etc.
• Patient contraindicated to contrast MRI scans. E.g. claustrophobia, allergy to gadolinium contrast, MRI incompatible implants, estimated glomerular filtration rate of \< 30mL/min/1.73m2.

Sponsors & Collaborators

• Chinese University of Hong Kong: lead

Study Sites (1)

Chinese University of Hong Kong

Hong Kong, Hong Kong

Location

MeSH Terms

Conditions

Antiphospholipid Syndrome; Constriction, Pathologic

Interventions

Hematologic Tests

Condition Hierarchy (Ancestors)

Autoimmune Diseases; Immune System Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Bonaventure Yiu Ming IP, MB ChB

  Chinese University of Hong Kong

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: October 13, 2022
• First Posted: October 17, 2022
• Study Start: October 12, 2022
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): July 17, 2027
• Last Updated: May 26, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)