Observational Dutch Young Symptomatic StrokE studY - nEXT

NCT05853796 | Recruiting DMC

• 1 other identifier: NL77518.091.21
• Study Type: observational
• Target: 280
• Locations: 1 country
• Sites: 6

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. 1.Baseline and 3 months coagulation profile:
2. 2.Baseline and 3 months inflammation/endothelial activation profile:
3. 3.Vessel wall enhancement on 3 Tesla MRI
4. 4.Questionnaire trigger factors

Conditions

Ischemic Stroke; Stroke in the Young; Cardiovascular Diseases; Cerebrovascular Disorders; Embolism and Thrombosis; Thrombophilia; Coagulation

Outcome Measures

Primary Outcomes (1)

• Difference of concentration biomarkers and coagulation assays between patients and controls

  Biomarkers and assays of coagulation, inflammation and endothelium activation

  At baseline and 3 month visit

Secondary Outcomes (6)

• Nonfatal or fatal recurrent cardiovascular (ischemic) events

  10 years

• Recurrent venous thrombotic events

  10 years

• Death from any cause

  10 years

• Malignancy

  10 years

• Bleeding complications

  10 years

Other Outcomes (4)

• 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 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

Study Arms (2)

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

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Patients aged 18 to 49 hospitalized due to first-ever imaging-positive ischemic stroke or transient ischemic attack.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Radboud University Medical Center: lead
• Synapse bv: collaborator

Study Sites (6)

Radboudumc

Nijmegen, Gelderland, 6525 GA, Netherlands

RECRUITING

Catharina Ziekenhuis

Eindhoven, North Brabant, 5623 EJ, Netherlands

NOT YET RECRUITING

Medisch Spectrum Twente

Enschede, Overijssel, 7512 KZ, Netherlands

NOT YET RECRUITING

Isala

Zwolle, Overijssel, 8025 AB, Netherlands

NOT YET RECRUITING

HagaZiekenhuis

The Hague, South Holland, 2545 AA, Netherlands

NOT YET RECRUITING

Medisch Centrum Leeuwarden

Leeuwarden, 8934 AD, Netherlands

NOT YET RECRUITING

Related Publications (1)

• Spiegelenberg JP, Verburgt E, den Hertog H, de Laat KF, van Rooij FG, van Uden IWM, Arntz RM, van den Wijngaard IR, Kessels RPC, Piai V, van der Kolk A, Roest M, de Laat B, Middeldorp S, Tuladhar A, Leentjens J, de Leeuw FE. Role of inflammation and haemostasis on aetiology and prognosis in young patients with ischaemic stroke: study protocol of the Observational Dutch Young Symptomatic StrokE study-EXTended (ODYSSEY-nEXT) - a multicentre prospective cohort study. BMJ Open. 2025 Mar 21;15(3):e096330. doi: 10.1136/bmjopen-2024-096330.

  PMID: 40118475 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Patients and controls at baseline: 1 x 2.7 mL + 1 x 9ml sodium citrate tube, aliquoted in 4 x 1000 µL cryovials; 1 x 5 mL serum tube, aliquoted in 3 x 500 µL sterile cryovials; 1 x 3 mL EDTA tube, aliquoted in 3 x 500 µL cryovials; For 20 patients and 20 controls from the Radboudumc the following tubes were addionally collected for whole blood analysis: 1x 2.7 ml citrate tube 3 x 10 ml EDTA tube for PBMCs isolation and storage. Patients at 3-month visit: 1 x 2.7 mL + 1 x 9ml sodium citrate tube, aliquoted in 4 x 1000 µL cryovials; 1 x 5 mL serum tube, aliquoted in 3 x 500 µL sterile cryovials; 1 x 3 mL EDTA tube, aliquoted in 3 x 500 µL cryovials; For 20 patients and 20 controls from the Radboudumc the following tubes were addionally collected for whole blood analysis: 1x 2.7 ml citrate tube 3 x 10 ml EDTA tube for PBMCs isolation and storage.

MeSH Terms

Conditions

Ischemic Stroke; Cardiovascular Diseases; Cerebrovascular Disorders; Embolism and Thrombosis; Thrombophilia; Thrombosis

Condition Hierarchy (Ancestors)

Stroke; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Central Study Contacts

Frank-Erik De Leeuw, Prof.

CONTACT

0031650200314; frankerik.deleeuw@radboudumc.nl

Janneke Spiegelenberg, MD

CONTACT

janneke.spiegelenberg@radboudumc.nl

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2023
• First Posted: May 11, 2023
• Study Start: February 6, 2023
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2037
• Last Updated: May 11, 2023

Record last verified: 2023-05

Locations

NL (6)