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Active, not recruitingNCT03609437ESUSUpdated Jul 15, 2025

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

An observational study in Embolic Stroke of Undetermined Source and Endothelial Dysfunction, sponsored by University of Athens. Active, not recruiting at 1 site in Greece. Open to participants aged 18 Years to 75 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-07-15.

Sponsored by University of Athens · Observational

Study type
Observational
Model
Case-control
Time perspective
Prospective
Enrollment
215
Ages
18 Years to 75 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Embolic Stroke of Undetermined Source
  • Endothelial Dysfunction

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Keywords

  • Embolic stroke
  • Arterial stiffness
  • Endothelial function
  • Endothelial glycocalyx
  • Left ventricular function
  • Oxidative stress
03

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
Yes
Sampling method
Non-probability sample

Study population

The study population will consist of 172 consecutive patients with Ischemic stroke of undetermined source (ESUS) that fulfill inclusion criteria and 43 healthy volunteers of similar age and sex (control group)

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

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.
04

Study design

Observational model
Case-control
Time perspective
Prospective
Enrollment
215 participants (estimated)
Patient registry
No
Biospecimen retention
Samples without dna

Groups and cohorts

  • ESUS patients

    Acute ischemic stroke patients satisfying embolic stroke of undetermined source (ESUS) diagnostic criteria.

  • Controls

    Healthy volunteers (colleagues, friends, relatives and others).

  • Lacunar stroke patients

    Acute ischemic stroke patients satisfying lacunar stroke diagnostic criteria

  • Cardioembolic stroke patients

    Acute ischemic stroke patients satisfying cardioembolic stroke diagnostic criteria

  • Atherosclerotic stroke patients

    Acute ischemic stroke patients satisfying atherosclerotic stroke diagnostic criteria

05

What researchers measure

Primary outcomes

  1. Comparison of endothelial glycocalyx thickness between patients with embolic stroke of undetermined source (ESUS), cardioembolic, atherosclerotic, lacunar strokes and controls

    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.

    Time frame: Baseline

Secondary outcomes

  1. Comparison of arterial stiffness between patients with embolic stroke of undetermined source (ESUS), cardioembolic, atherosclerotic, lacunar strokes and controls.

    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.

    Time frame: Baseline

  2. Assessment of left ventricular performance in patients with embolic stroke of undetermined source (ESUS), cardioembolic, atherosclerotic, lacunar strokes and controls.

    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.

    Time frame: Baseline

  3. Serum malondialdehyde levels in patients with embolic stroke of undetermined source (ESUS), cardioembolic, atherosclerotic, lacunar strokes and controls.

    Investigators plan to compare serum malondialdehyde levels in patients with embolic stroke of undetermined source (ESUS) and controls.

    Time frame: Baseline

  4. Assessment of left atrial performance in patients with embolic stroke of undetermined source (ESUS), cardioembolic, atherosclerotic, lacunar strokes and controls.

    Investigators plan to compare left atrial strain (LA strain) in patients with embolic stroke of undetermined source (ESUS), cardioembolic, atherosclerotic, lacunar strokes and controls.

    Time frame: Baseline

06

Study locations

1 site
  • Konstantinos Katogiannis
    Athens, Attica 12461, Greece
07

References and documents

Publications

  • Ikonomidis I, Frogoudaki A, Vrettou AR, Andreou I, Palaiodimou L, Katogiannis K, Liantinioti C, Vlastos D, Zervas P, Varoudi M, Lambadiari V, Triantafyllidi H, Pavlidis G, Efentakis P, Tsoumani M, Tsantes AE, Parissis J, Revela I, Andreadou I, Tsivgoulis G. Impaired Arterial Elastic Properties and Endothelial Glycocalyx in Patients with Embolic Stroke of Undetermined Source. Thromb Haemost. 2019 Nov;119(11):1860-1868. doi: 10.1055/s-0039-1694752. Epub 2019 Aug 17. PubMed 31421641 ↗

Individual participant data

Plan to share: Undecided

08

Registry details

Key details

Study ID
NCT03609437
Lead sponsor
University of Athens
Responsible party
Ignatios Ikonomidis (Dr Ignatios Ikonomidis,MD,PhD,FESC Associate Professor, University of Athens) — Principal investigator
First posted
Aug 1, 2018
Start date
Jan 1, 2018
Primary completion
Oct 30, 2025 (estimated)
Completion
Jun 30, 2026 (estimated)
Last update
Jul 15, 2025

Study contacts

Ignatios Ikonomidis
principal investigator · University of Athens

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is active, not recruiting, as verified in Jul 2025. You cannot join it, but the record below documents what was studied.

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