Paroxysmal Nocturnal Hemoglobinuria in ESUS & ETUS

NCT03329365 | Active Not Recruiting

• 1 other identifier: HSREB109061
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired clonal hematological disorder, which can cause arterial or venous thrombosis. The frequency of PNH in young patients (\< 50 years old) with embolic stroke (ESUS), transient ischemic attack (ETUS) or superior sagittal sinus cerebral venous thrombosis (SSS-CVTUS) of undetermined source, is currently unknown. This study proposes to recruit ESUS, ETUS, SSS-CVTUS patients to determine the frequency of PNH diagnosis confirmed by flow cytometry in these patient populations.

Conditions

Paroxysmal Nocturnal Hemoglobinuria; Embolic Stroke of Undetermined Source; Transient Ischemic Attack; Cerebral Vein Thrombosis

Keywords

Flow cytometry; Lactate dehydrogenase (LDH) release; Anemia; Cytopenia

Outcome Measures

Primary Outcomes (1)

• Frequency of PNH in ESUS/ETUS/SSS-CVTUS

  Percentage of patients with flow-cytometry-confirmed PNH

  At recruitment

Secondary Outcomes (2)

• Frequency of PNH in ESUS/ETUS

  At recruitment

• Frequency of PNH in SSS-CVT

  At recruitment

Study Arms (2)

ESUS/ETUS

Patients with embolic ischemic stroke or transient ischemic attack of undetermined source

SSS-CVTUS

Patients with superior sagittal sinus cerebral venous thrombosis of undetermined source

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Patients with ESUS, ETUS, or SSS-CVTUS attending the Urgent TIA and Stroke Prevention Clinic or admitted to University or Victoria Hospital, in London, Ontario, Canada.

You may qualify if:

• General:
• Participants with embolic ischemic stroke (ESUS), embolic transient ischemic attack (ETUS) or cerebral venous thrombosis (CVTUS) of undetermined source.
• For transient ischemic attack (TIA):
• One of the following criteria needs to be fulfilled to be considered as embolic TIA:
• Focal symptoms suggesting involvement of de cerebral cortex in the middle cerebral artery (MCA) territory (e.g., aphasia, neglect, apraxia, dystextia, anosognosia, isolated leg, arm or hand weakness). Some of these symptoms have been described as associated with subcortical fibers connecting cortical areas as well but, despite this, they are usually related to cortical localizations. Patients with hemianopia will be included only if hemianopia is not the primary symptom or an isolated symptom.
• Rapidly resolving hemispheric symptoms. This concept comprises two components: (a) sudden onset hemispheric syndrome: sudden onset of symptoms and signs implicating extensive ischemia in the internal carotid artery (ICA) or MCA territories, including hemiparesis, hemianopia, conjugate eye deviation, other cortical signs, or altered consciousness; and (b) spectacular shrinking deficit: improvement within 24 hours (approximately).
• Symptoms involving more than one vascular territory within a single hemisphere (e.g. left sided weakness + left homonymous hemianopia) or both (e.g., left sided weakness and aphasia in a right-handed patient).
• Simultaneous embolization to other organs (e.g., bowel, spleen, liver, kidneys, toes).
• Transient monocular blindness (amaurosis fugax) with no evidence of giant cell arteritis (e.g., normal erythrocyte sedimentation rate).
• No definite cortical symptoms but neuroimaging evidence of prior (chronic) typical infarct (wedge shaped, involving the cerebral cortex).
• All of the following criteria must be fulfilled to be considered as TIA of undetermined source:
• No neuroimaging evidence of an acute brain infarct within the brain region(s) responsible for the presenting symptoms.
• Absence of extracranial or intracranial atherosclerosis causing ≥50% luminal stenosis in arteries supplying the area of ischemia.
• No major-risk cardioembolic source of embolism.
• No other specific cause of stroke identified (e.g., arteritis, dissection, migraine, vasospasm, or drug abuse).

You may not qualify if:

• General:
• Inability to provide informed consent
• For stroke patients:
• Evidence of \>50% stenosis of the internal carotid artery (ICA) or MCA ipsilateral to the qualifying ischemic stroke on neurovascular imaging studies.
• Ischemic stroke involving deep structures and measuring \< 15 mm on diffusion-weighted (DWI) magnetic resonance imaging (MRI). Cortical strokes measuring \<15 mm will qualify to be included in the study.
• Evidence of a cause explaining the stroke (e.g. hypercoagulable state or any other major source of cardiac embolism).
• For TIA patients:
• Patients no fulfilling the criteria for ETUS.
• For cerebral venous thrombosis patients:
• Subjects without involvement of the superior sagittal sinus (SSS)
• Subjects with an evident cause explaining the thrombosis (e.g., thrombophilia)

Sponsors & Collaborators

• London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's: lead
• Alexion Pharmaceuticals, Inc.: collaborator

Study Sites (1)

London Health Sciences Centre

London, Ontario, N6A5A5, Canada

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Plasma

MeSH Terms

Conditions

Hemoglobinuria, Paroxysmal; Ischemic Attack, Transient; Intracranial Thrombosis; Anemia; Cytopenia

Condition Hierarchy (Ancestors)

Anemia, Hemolytic; Hematologic Diseases; Hemic and Lymphatic Diseases; Myelodysplastic Syndromes; Bone Marrow Diseases; Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Intracranial Embolism and Thrombosis; Thromboembolism; Embolism and Thrombosis

Study Officials

• Luciano A Sposato, MD

  London Health Sciences Center, Western University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 30, 2017
• First Posted: November 6, 2017
• Study Start: November 1, 2018
• Primary Completion: March 29, 2023
• Study Completion: March 29, 2025
• Last Updated: October 8, 2024

Record last verified: 2024-03

Locations

CA (1)