Embolic Stroke of Undetermined SourceESUSNCT03609437
Impaired Endothelial Integrity in Patients With Embolic Stroke of Undetermined Source (ESUS)
An observational study of Embolic Stroke of Undetermined Source and Endothelial Dysfunction, run by University of Athens at 1 site in Greece.
Trial 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 more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Embolic Stroke of Undetermined Source, Endothelial Dysfunction
- How many people
- 215 participants
- Where
- 1 siteGreece
- Study dates
- 1 Jan 2018to 30 Jun 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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)
Who may be able to join
- 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.
Who cannot join
- presence of acute haemorrhagic stroke,
- the presence of stroke of other determined etiology,
- the history of previous Ischemic stroke and/or Myocardial Infarction (MI),
- hypercoagulable state,
- active malignancy
- severe chronic kidney disease (eGFR<30 ml/minute). These exclusion criteria are applied to both patients and control subjects.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Impaired Endothelial Glycocalyx Integrity and Arterial Elastic Properties in Patients With Embolic Stroke of Undetermined Source (ESUS)
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.
- Keywords
- Embolic stroke, Arterial stiffness, Endothelial function, Endothelial glycocalyx, Left ventricular function, Oxidative stress
- Medical subject headings
- Embolic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline
Secondary outcomes (4)
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.
Measured: Baseline
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.
Measured: Baseline
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.
Measured: Baseline
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.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2018
- Study start1 Jan 2018
- Primary completion30 Oct 2025 (estimated)
- Study completion30 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Embolic Stroke of Undetermined SourceStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 215 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Athens
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ignatios Ikonomidis, University of Athens
- Investigators
- Ignatios Ikonomidis, Principal investigator, University of Athens
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03609437
- Sponsor's protocol ID
- esus-endothelium-attikon
- Acronym
- ESUS
- Status last verified
- Jul 2025
- First submitted
- 15 Jul 2018
- Last updated
- 15 Jul 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
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
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impaired Endothelial Glycocalyx Integrity and Arterial Elastic Properties in Patients With Embolic Stroke of Undetermined Source (ESUS)
- ClinicalTrials.gov ID
- NCT03609437
- Acronym / sponsor ID
- ESUS / esus-endothelium-attikon
- Keywords
- Embolic stroke, Arterial stiffness, Endothelial function, Endothelial glycocalyx, Left ventricular function, Oxidative stress
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 215 participants (estimated)
- Lead sponsor
- University of AthensUniversity, hospital or other
- Study start
- 1 Jan 2018 (actual)
- Primary completion
- 30 Oct 2025 (estimated)
- Study completion
- 30 Jun 2026 (estimated)
- First posted
- 1 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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)
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (6 listed)
- presence of acute haemorrhagic stroke,
- the presence of stroke of other determined etiology,
- the history of previous Ischemic stroke and/or Myocardial Infarction (MI),
- hypercoagulable state,
- active malignancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Comparison of endothelial glycocalyx thickness between patients with embolic stroke of undetermined source (ESUS), cardioembolic, atherosclerotic, lacunar strokes and controls
Time frame: 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.
4 secondary outcomes
Comparison of arterial stiffness between patients with embolic stroke of undetermined source (ESUS), cardioembolic, atherosclerotic, lacunar strokes and controls.
Time frame: Baseline
Assessment of left ventricular performance in patients with embolic stroke of undetermined source (ESUS), cardioembolic, atherosclerotic, lacunar strokes and controls.
Time frame: Baseline
Serum malondialdehyde levels in patients with embolic stroke of undetermined source (ESUS), cardioembolic, atherosclerotic, lacunar strokes and controls.
Time frame: Baseline
Assessment of left atrial performance in patients with embolic stroke of undetermined source (ESUS), cardioembolic, atherosclerotic, lacunar strokes and controls.
Time frame: Baseline
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2025.
- Derived from this study: PubMed 31421641Ikonomidis 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ignatios Ikonomidis principal investigator
University of Athens
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Embolic Stroke of Undetermined Source and Endothelial Dysfunction, run by University of Athens at 1 site in Greece.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 15 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Greece. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Comparison of endothelial glycocalyx thickness between patients with embolic stroke of undetermined source (ESUS), cardioembolic, atherosclerotic, lacunar strokes and controls (time frame: Baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03609437, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jul 2025.