Prevalence and Etiologies of Intracranial Stenosis in Patients With Antiphospholipid Syndrome

NCT ID: NCT05583305

Last Updated: 2025-07-01

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Total Enrollment: 60 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-10-12
• Study Completion Date: 2026-07-17

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.

Detailed Description

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.

Upon reviewing the clinical and laboratory information in the medical specialist out-patient clinics, electronic patient record and/or through the Clinical Data Analysis And Reporting System (CDARS), investigators shall identify and recruit on-site APS patients who fulfilled the modified Sapporo criteria, currently aged ≥18 years, and receive care from the Prince of Wales Hospital.

Investigators shall then arrange a study clinic visit for eligible patients. After obtaining an informed consent, patients will be subjected to cognitive assessment (Hong Kong Version of Montreal Cognitive Assessment (HK-MoCA)), blood pressure, pulse, body mass index measurement, urinalysis, and contrast MRI brain (see imaging assessment below). Demographic data (age, gender, smoking, drinking, ambulatory status), medical comorbidities (concurrent autoimmune diseases and their organ involvement, history of catastrophic APS, hypertension, hyperlipidemia, diabetes mellitus, congestive heart failure, number and type of previous arterial or venous thromboembolism), laboratory parameters (complete blood count, liver and renal function test, C-reactive protein, erythrocyte sediment rate, high sensitive C-reaction protein, plasminogen activator inhibitor-1, neurofilament light chain, titers of autoimmune markers including anti-nuclear antibodies, extractable nuclear antigen antibodies, aPLs, rheumatoid factor, anti-cyclic citrullinated peptide antibody, etc.), concurrent medications (aspirin, warfarin, direct oral anticoagulants, antihypertensives, statins, steroid, immunosuppressants, etc.). In another 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. They will be assessed in the same manner as the APS patients.

Conditions

Antiphospholipid Syndrome; Stenosis; Intracranial Stenosis

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

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

Imaging assessment

Intervention Type: 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.

Neurosonology assessment

Intervention Type: 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.

Blood Test

Intervention Type: 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

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

Imaging assessment

Intervention Type: 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.

Neurosonology assessment

Intervention Type: 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.

Blood Test

Intervention Type: 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.

Interventions

Imaging assessment

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.

Intervention Type: DIAGNOSTIC_TEST

Neurosonology assessment

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.

Intervention Type: DIAGNOSTIC_TEST

Blood 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.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

1. Patients 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

Exclusion Criteria

1. Patient with established neurological disease, such as stroke, cerebral venous thrombosis, vasculitis of the central nervous system, cerebral lupus, etc.

2. 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chinese University of Hong Kong

OTHER

Sponsor Role: lead

Responsible Party

Dr. IP Yiu Ming Bonaventure

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Bonaventure Yiu Ming IP, MB ChB

Role: PRINCIPAL_INVESTIGATOR

Chinese University of Hong Kong

Locations

Chinese University of Hong Kong

Hong Kong, , Hong Kong

Countries

Hong Kong

Other Identifiers

CREC 2022.352

Identifier Type: -

Identifier Source: org_study_id