Extracellular Vesicle Surface Markers In Acute Cerebrovascular Syndromes.

NCT06319742 | Recruiting

• 1 other identifier: NSISTRCR_2201
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Clinical implication of eventual blood biomarkers for stroke diagnosis and prognosis would be limited, mainly because clinical evaluation and scales (providing stroke severity) or neuroimaging (providing accurate size of the lesion) are more reliable predictors for clinical outcome prediction. In clinical practice, it would be more useful to find a biomarker, which can help to orientate the physician in conditions in which the clinical picture and imaging provide a limited support. Transient Ischemic Attacks (TIAs) represent a classical example for which a biomarker would be of interest to confirm and distinguish a brain ischemic process from a stroke mimic. Diagnostic biomarkers of TIA have been investigated, but none of the potential candidates reached enough accuracy for TIA diagnosis. Our group has found that Extracellular Vesicles (EVs) could be useful as biomarkers for detecting brain ischemia in patients with TIA because the EV-surface antigen profile appears to be different in patients with transient symptoms, adjudicated to be very likely caused by brain ischemia, compared to patients whose symptoms were less likely to due to brain ischemia. Our study has raised interest in the scientific community recognizing the promising role of of blood-derived EVs analysis in expanding the possibilities to correctly diagnose and classify TIA and stroke events, discriminate them from TIA or stroke mimics, with important future implications in management and therapy of the patients with acute ischemic cerebrovascular syndrome. the validity of our approach needs to be tested in a larger, prospective, multicenter study.

Conditions

Stroke, TIA, Stroke-mimics, Stroke Biomarkers

Outcome Measures

Primary Outcomes (1)

• TIA differentiation from TIA mimics

  determine the performance of EV profiling (analysis of antigens expressed on vesicles surface), added to a structured clinical (PREDISC score) and imaging evaluation (brain MRI), to discriminate TIAs from TIA mimics (non ischemic events).

  72 hours from symptoms onset

Secondary Outcomes (2)

• TIA differentiation from Stroke

  acute phase, 3 and 12 months

• Stroke etiology

  acute phase, 3 and 12 months

Study Arms (3)

Stroke

Diagnostic Test: Extracellular vescicles (EV) analysis

TIA

Diagnostic Test: Extracellular vescicles (EV) analysis

Stroke Mimic

Diagnostic Test: Extracellular vescicles (EV) analysis

Interventions

Extracellular vescicles (EV) analysis DIAGNOSTIC_TEST

The patients undergo a blood sample for EV analyses: EVs will be characterized by nanoparticle tracking analysis, western blot, bead-based flow cytometry (direct and inverse approach), and ELISA. We will evaluate diameter and concentration of serum nanoparticles (NPs) by nanoparticle tracking analysis (NTA) using NanoSight LM10. Western Blot analysis will be performed on protein lysate after EV immuno-capture (using beads covered with antibodies against EV specific tetraspanins, CD9, CD63 and CD81). EV profiling will be performed using a standardized multiplex bead-based flow cytometric assay, using MACSPlex Human Exosome Kit (Miltenyi Biotec; Bergisch Gladbach, Germany), as previously described. 22 The detection of 37 different surface antigens commonly expressed on EV membrane (including markers from activated platelets, endothelium, and inflammatory cells) will be simultaneously performed.

Stroke; Stroke Mimic; TIA

Eligibility Criteria

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

Study Population

We will enroll all patients admitted to the stroke Units because of symptoms suggesting a cerebrovascular syndrome

You may qualify if:

• Affected by:
• I. Suspect ischemic minor stroke (acute loss of focal cerebral function of presumed vascular etiology and NIHSS ≤327, 28) within 48 hours of symptoms onset or II. TIA (defined as the acute onset of focal neurological symptoms lasting \<24 h and presumed to be caused by brain ischemia at the time of referral)19 III. Symptoms mimicking I. or II. with but with high suspition of a non-ischemic condition being the cause of the event;
• \) age ≥18 years; 3) if cerebral magnetic resonance imaging will be performed within 48-72 hours from admission; 4) if baseline CT/MRI is without hemorrhage; 5) if informed consent obtained.

You may not qualify if:

• ocular TIA (amaurosis fugax);
• contraindications for MRI;
• pregnancy;
• concomitant acute/chronic inflammatory disease (e.g., infections, autoimmune disease);
• concomitant hematological diseases;
• Central Nervous System infection within 30 days;
• serious head trauma within 30 days;
• major surgery within 90 days.

Sponsors & Collaborators

• Ospedale Civico, Lugano: lead

Study Sites (1)

Neurocenter of Southern Switzerland, Ospedale Civico

Lugano, Canton Ticino, CH-6900, Switzerland

RECRUITING

MeSH Terms

Conditions

Stroke; Ischemic Attack, Transient

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Brain Ischemia

Central Study Contacts

Carlo Walter Cereda, PI

CONTACT

+41918116691; carlo.cereda@eoc.ch

Giovanni Bianco

CONTACT

+41918117073; giovanni.bianco@eoc.ch

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. med.

Study Record Dates

• First Submitted: March 13, 2024
• First Posted: March 20, 2024
• Study Start: November 18, 2022
• Primary Completion: December 31, 2025
• Study Completion: January 31, 2026
• Last Updated: April 18, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)