Prevalence and Etiologies of Intracranial Stenosis in Patients With Antiphospholipid Syndrome

• Conditions: Intracranial Stenosis; Stenosis; Antiphospholipid Syndrome
• Interventions: Diagnostic Test: Imaging assessment; Diagnostic Test: Neurosonology assessment; Diagnostic Test: Blood Test

• Registration Number: NCT05583305
• Lead Sponsor: Chinese University of Hong Kong

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.

Study Timeline

• Study Start: 2022-10-12
• Study First Submitted: 2022-10-13
• Study First Submitted QC: 2022-10-13
• Study First Posted: 2022-10-17
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-01
• Last Update Posted: 2024-05-03
• Primary Completion: 2026-01-31
• Study Completion: 2026-07-17

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 60

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

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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.

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Controls	Neurosonology assessment	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
Patients diagnosed with APS	Imaging assessment	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
Patients diagnosed with APS	Blood Test	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
Controls	Imaging assessment	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
Patients diagnosed with APS	Neurosonology assessment	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
Controls	Blood Test	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

Primary Outcome Measures

Name	Time	Method
Radiological evidence of intracranial arterial stenosis	31／01／2026	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.

Secondary Outcome Measures

Name	Time	Method
Other radiological outcomes	31／01／2026	Including the presence and pattern of enhancing intracranial plaques (concentric vs eccentric), Age-related White Matter Change Scale ≥ 2, white matter hyperintensity volume, presence of lacunes, cerebral microbleeds, extracranial ICA plaques, normalized total brain volume. Secondary biochemical outcomes include level of hs-CRP and PAI-1. The relationship between the neuroimaging outcomes and the clinical characteristics of patients with APS will be evaluated.

Trial Locations

Locations (1)

Chinese University of Hong Kong; 🇭🇰 Hong Kong, Hong Kong