ODYSSEY-nEXT: Observational Dutch Young Symptomatic StrokE studY - nEXT

Sponsor

Radboud University Medical Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT05853796

Collaborator

Synapse bv (Industry)

280

Enrollment

Locations

166.8

Anticipated Duration (Months)

46.7

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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:

Baseline and 3 months coagulation profile:

Whole blood and platelet poor plasma thrombin generation, platelet function tests, and coagulation biomarkers, screening for thrombophilia.

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.

Vessel wall enhancement on 3 Tesla MRI
Questionnaire trigger factors

Condition or Disease	Intervention/Treatment	Phase
Ischemic Stroke Stroke in the Young Cardiovascular Diseases Cerebrovascular Disorders Embolism and Thrombosis Thrombophilia Coagulation

Study Design

Study Type:

Observational

Anticipated Enrollment :

280 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

Observational Dutch Young Symptomatic StrokE studY - Extended

Actual Study Start Date :

Feb 6, 2023

Anticipated Primary Completion Date :

Jan 1, 2027

Anticipated Study Completion Date :

Jan 1, 2037

Arms and Interventions

Arm	Intervention/Treatment
Patients with acute ischemic stroke at young age (18-50 years) Patients aged 18 to 50 years with first-ever ischemic stroke or transient ischemic attack.
Healthy controls Healthy controls (aged 18 to 50 years) without cardiovascular diseases in their medical history. Subjects age- and gender-matched to patients

Outcome Measures

Primary Outcome Measures

Difference of concentration biomarkers and coagulation assays between patients and controls [At baseline and 3 month visit]
Biomarkers and assays of coagulation, inflammation and endothelium activation

Secondary Outcome Measures

Nonfatal or fatal recurrent cardiovascular (ischemic) events [10 years]
Ischemic stroke or transient ischemic attack, acute coronary syndrome, peripheral artery disease
Recurrent venous thrombotic events [10 years]
Deep venous thrombosis, pulmonary embolism, cerebral venous sinus thrombosis
Death from any cause [10 years]
Malignancy [10 years]
Bleeding complications [10 years]
Minor and major bleeding complications
Vessel wall imaging on 3T MRI [At baseline]
Detection of vessel wall enhancement on MRI in young stroke patients

Other Outcome Measures

Modified Rankin Scale [at 3-month visit and at annual follow-up contacts from year 1 to year 10]
Functional outcome will be assessed with modified Rankin Scale
Functional outcome will be assessed with Barthel Index [at 3-month visit and at annual follow-up contacts from year 1 to year 10.]
Coping strategies [at 3 months visit and 6 months]
Questionnaire about different strategies to cope with major setbacks.
Subjective cognitive outcome [at 6-month follow-up]
Subjective cognition will be assessed with an electronic questionnaire

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

All

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Radboudumc	Nijmegen	Gelderland	Netherlands	6525 GA
2	Catharina Ziekenhuis	Eindhoven	Noord-Brabant	Netherlands	5623 EJ
3	Medisch Spectrum Twente	Enschede	Overijssel	Netherlands	7512 KZ
4	Isala	Zwolle	Overijssel	Netherlands	8025 AB
5	HagaZiekenhuis	Den Haag	Zuid-Holland	Netherlands	2545 AA
6	Medisch Centrum Leeuwarden	Leeuwarden		Netherlands	8934 AD