Impaired Endothelial Integrity in Patients With Embolic Stroke of Undetermined Source (ESUS)

Active, not recruiting

• Conditions: Endothelial Dysfunction; Embolic Stroke of Undetermined Source

• Registration Number: NCT03609437
• Lead Sponsor: University of Athens

Brief Summary

The investigators will measure endothelial glycocalyx, aortic elastic properties, oxidative stress, and their association with left ventricular (LV) and left atrial (LA) function in ESUS, cardioembolic, atherosclerotic, lacunar strokes and age- and sex-adjusted healthy individuals.

Detailed Description

Investigators plan to include male and female patients, aged 18 to 75 years old admitted and hospitalized in the 2nd Neurology Department of Attikon University Hospital for Acute Ischemic Stroke, based on the Trial of Org 10172 in Acute Stroke Treatment TOAST classification. The TOAST classification consists of five categories: 1) large artery atherosclerosis (atherothrombotic), 2) cardioembolic, 3) small artery occlusion (lacunar), 4) stroke of undetermined etiology (ESUS).

In participants (patients and controls) the investigators plan to measure and compare: a) perfused boundary region (PBR) of the sublingual arterial microvessels (range 5-25 micrometers), a marker inversely related with glycocalyx thickness, b) pulse wave velocity (PWV), central systolic blood pressure (cSBP) and augmentation index (AIx), c) LV Global Longitudinal strain (GLS), d) LA volume and strain using speckle-tracking strain imaging, e) Malondialdehyde (MDA), as an oxidative stress marker.

Study Timeline

• Study Start: 2018-01-01
• Study First Submitted: 2018-07-15
• Study First Submitted QC: 2018-07-24
• Study First Posted: 2018-08-01
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-10
• Last Update Posted: 2025-07-15
• Primary Completion: 2025-10-30
• Study Completion: 2026-06-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 215

Inclusion Criteria

The investigators plan to include participants with Acute Ischemic Stroke, based on the TOAST classification : 1) large artery atherosclerosis (atherothrombotic), 2) cardioembolic, 3) small artery occlusion (lacunar), 4) stroke of undetermined etiology (ESUS). According to the TOAST classification, diagnoses are based on clinical presentation and on data collected by exams such as brain imaging (CT/MRI), cardiac imaging (echocardiography) and laboratory tests for the prothrombotic state. The diagnosis of Embolic Stroke of Undetermined Source (ESUS) was established based on the criteria defined by the Cryptogenic Stroke/ESUS International Working Group.

Exclusion Criteria

1. presence of acute haemorrhagic stroke,
2. the presence of stroke of other determined etiology,
3. the history of previous Ischemic stroke and/or Myocardial Infarction (MI),
4. hypercoagulable state,
5. active malignancy
6. severe chronic kidney disease (eGFR<30 ml/minute). These exclusion criteria are applied to both patients and control subjects.

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Comparison of endothelial glycocalyx thickness between patients with embolic stroke of undetermined source (ESUS), cardioembolic, atherosclerotic, lacunar strokes and controls	Baseline	Investigators will assess endothelial glycocalyx thickness by evaluating perfused boundary region (PBR, micrometers) of the sublingual arterial microvessels (range 5-25 micrometers) for patients with embolic stroke of undetermined source (ESUS), cardioembolic, atherosclerotic, lacunar strokes and controls.

Secondary Outcome Measures

Name	Time	Method
Comparison of arterial stiffness between patients with embolic stroke of undetermined source (ESUS), cardioembolic, atherosclerotic, lacunar strokes and controls.	Baseline	Investigators aim to evaluate arterial stiffness by pulse wave velocity (PWV,m/sec) using tonometry in patients with embolic stroke of undetermined source (ESUS), cardioembolic, atherosclerotic, lacunar strokes and controls.
Assessment of left ventricular performance in patients with embolic stroke of undetermined source (ESUS), cardioembolic, atherosclerotic, lacunar strokes and controls.	Baseline	Investigators plan to assess left ventricular global longitudinal strain (GLS, %) in patients with embolic stroke of undetermined source (ESUS), cardioembolic, atherosclerotic, lacunar strokes and controls.
Serum malondialdehyde levels in patients with embolic stroke of undetermined source (ESUS), cardioembolic, atherosclerotic, lacunar strokes and controls.	Baseline	Investigators plan to compare serum malondialdehyde levels in patients with embolic stroke of undetermined source (ESUS) and controls.
Assessment of left atrial performance in patients with embolic stroke of undetermined source (ESUS), cardioembolic, atherosclerotic, lacunar strokes and controls.	Baseline	Investigators plan to compare left atrial strain (LA strain) in patients with embolic stroke of undetermined source (ESUS), cardioembolic, atherosclerotic, lacunar strokes and controls.

Trial Locations

Locations (1)

Konstantinos Katogiannis; 🇬🇷 Athens, Attiki, Greece