Clinical trial NCT05853796: Observational Dutch Young Symptomatic StrokE studY - nEXT
Official title: Observational Dutch Young Symptomatic StrokE studY - Extended
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Ischemic Stroke
Stroke in the Young
Cardiovascular Diseases
Cerebrovascular Disorders
Embolism and Thrombosis
Thrombophilia
Coagulation
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: Synapse bv
First posted: 2023-05-11
Enrollment: 280
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients aged 18 to 49 hospitalized due to first-ever imaging-positive ischemic stroke or transient ischemic attack.

Brief summary: BACKGROUND: Worldwide, 2 million patients aged 18-50 years suffer an ischemic stroke each year with an increasing trend over the past decade due to yet unknown reasons. Whereas prognosis and antithrombotic treatment in older patients with cardiovascular disease are among the best studied topics in clinical medicine, this does not hold true for patients at young age. It is of great importance to treat these patient groups correctly to prevent recurrence and bleeding complications. However, previous research have shown that there is a long-term increased risk of recurrent ischemic events despite the secondary prevention and a subsequent increased bleeding risk. To tailor effective antithrombotic therapy to the individual patient, it is essential to understand the underlying pathogenesis and identify modifiable risk factors in young patients for recurrence or bleeding. It is thought that abnormalities of hemostasis may play a key role in early-onset ischemic stroke. First, prothrombotic conditions are associated with an increased risk for ischemic stroke at young age. In addition, disturbance of the hemostatic balance due to one or several triggers can activate the coagulation cascade, which on its turn can lead or contribute to clot formation and subsequent arterial occlusion. In previous study, there were indications that trigger factors such as fever and/or an infection in the days prior to the stroke may play a role in the pathogenesis. This suggests that an interaction between inflammation, endothelial damage and coagulation may lead to the formation of a clot. In this observational study we aim to investigate the role of the immune system, endothelial damage and coagulation in the pathogenesis and prognosis of stroke in young patients.

OBJECTIVE: To investigate the role of hemostasis, inflammation and endothelial activation in the etiology and prognosis in an acute ischemic stroke (or TIA) in young stroke patients.

STUDY DESIGN: Multicentre prospective observational study

STUDY POPULATION:

All patients aged between 18 and 50 years old with a first-ever ischemic stroke or TIA who are admitted to the neurology ward or seen at the outpatient clinic of one of the participating centers.

Main exclusion criteria are: history of clinical TIA, ischemic stroke or intracerebral hemorrhage. A intracerebral hemorrhage resulting from trauma, known aneurysm or underlying intracerebral malignancy. A venous infarction, retinal infarction and amourosis fugax. Inadequate control of the Dutch language to reliably sign an informed consent from and/or participate in the follow-up. Patients are excluded if they have a contra indication for 3T MRI.

In addition 60 healthy controls (18-50 years old) will be included.

MAIN STUDY ENDPOINTS:

1. Baseline and 3 months coagulation profile:

   Whole blood and platelet poor plasma thrombin generation, platelet function tests, and coagulation biomarkers, screening for thrombophilia.
2. Baseline and 3 months inflammation/endothelial activation profile:

   Cytokines/chemokines, expression of receptors/cofactors related to hemostasis on peripheral blood mononuclear cells (PBMCs), stimulation tests of PBMC's to assess trained immunity.
3. Vessel wall enhancement on 3 Tesla MRI
4. Questionnaire trigger factors


Eligibility criteria: Inclusion Criteria:

* Patients with a first-ever transient ischemic attack (TIA) or acute ischemic stroke aged between 18 and 50 years old
* For this study, acute stroke is defined as "occurence of acute neurological deficit lasting more than 24 hours, with confirmation on imaging (CT(-a) or MR(-a))".TIA is defined as "occurence of acute neurological deficit lasting less than 24 hours with confirmation of ischemia on MRI).
* Patients have a kidney function eGFR\>30ml/min.

Exclusion Criteria:

* A history of clinical TIA, ischemic stroke or intracerebral hemorrhage
* A intracerebral hemorrhage resulting from trauma, known aneurysm or underlying intracerebral malignancy.
* A venous infarction, retinal infarction or amourosis fugax.
* Inadequate control of the Dutch language to reliably sign an informed consent from and/or participate in the follow-up
* Patients are excluded if they have a contra indication for 3T MRI.

Primary outcomes:
measure: Difference of concentration biomarkers and coagulation assays between patients and controls
timeFrame: At baseline and 3 month visit
Secondary outcomes:
measure: Nonfatal or fatal recurrent cardiovascular (ischemic) events
timeFrame: 10 years
measure: Recurrent venous thrombotic events
timeFrame: 10 years
measure: Death from any cause
timeFrame: 10 years
measure: Malignancy
timeFrame: 10 years
measure: Bleeding complications
timeFrame: 10 years
measure: Vessel wall imaging on 3T MRI
timeFrame: At baseline
Other outcomes:
measure: Modified Rankin Scale
timeFrame: at 3-month visit and at annual follow-up contacts from year 1 to year 10
measure: Functional outcome will be assessed with Barthel Index
timeFrame: at 3-month visit and at annual follow-up contacts from year 1 to year 10.
measure: Coping strategies
timeFrame: at 3 months visit and 6 months
measure: Subjective cognitive outcome
timeFrame: at 6-month follow-up
Locations:
city: Nijmegen
country: Netherlands
facility: Radboudumc
state: Gelderland
city: Eindhoven
country: Netherlands
facility: Catharina Ziekenhuis
state: Noord-Brabant
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente
state: Overijssel
city: Zwolle
country: Netherlands
facility: Isala
state: Overijssel
city: Den Haag
country: Netherlands
facility: HagaZiekenhuis
state: Zuid-Holland
city: Leeuwarden
country: Netherlands
facility: Medisch Centrum Leeuwarden
Study officials:
References: