Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome "SECRETO"

Recruiting

Phase N/A Results N/A

Trial Description

BACKGROUND: In industrialized countries a considerable and increasing proportion of strokes occur at younger ages. Stroke at young age causes marked disability at worst and thus long-standing socioeconomic consequences and exposes survivors for 4-fold risk of premature death compared with background population. Up to 50% of young patients with ischemic stroke remain without definitive etiology for their disease despite extensive modern diagnostic work-up (i.e. cryptogenic stroke). The group of cryptogenic strokes includes those with patent foramen ovale (PFO) or other abnormalities in the atrial septum in the heart as the only or concomitant finding. Population prevalence of PFO is high, 25%, and the mechanisms how PFO would be associated causally with ischemic stroke remain to be clarified. Moreover, there are only scarce data on clinical outcome, long-term risk of new vascular events, and prevention of such events in these patients.
DESIGN: Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO) is an international prospective multicenter case-control study of young adults (age 18-49) presenting with an imaging-positive first-ever ischemic stroke of undetermined etiology (aim N=2000). Patients are included after standardized diagnostic procedures (brain MRI, imaging of intracranial and extracranial vessels, cardiac imaging, and screening for coagulopathies) and age- and sex-matched to healthy controls in a 1:1 fashion. Up to 45 study sites worldwide will be needed to recruit the planned participant population during a 3-year period. Neurovascular imaging and echocardiography studies, and ECGs will be read centrally.
AIMS: SECRETO involves five principal fields of investigation: (1) Stroke triggers and clinical risk factors; (2) Long-term prognosis (new vascular events, functional and psychosocial outcomes); (3) Abnormalities of thrombosis and hemostasis; (4) Biomarkers of e.g. inflammation, atherogenesis, endothelial function, thrombosis, platelet activation, and hemodynamic stress to characterize postulated cryptogenic stroke mechanisms; and (5) genetic study, including genome-wide association and candidate gene studies as well as next-generation sequencing approach. All analyses consider cardiac functional and interatrial structural properties as a possible mediator. Furthermore, SECRETO Family Study (substudy) aims at collecting extensive family history of thrombotic events from informative patients being screened for SECRETO main study and collect genetic samples from all consenting family members for whole-genome sequencing.
SIGNIFICANCE: SECRETO will provide novel information on clinical and subclinical risk factors, both transient and chronic, predisposing to cryptogenic ischemic stroke in young adults. This study also reveals long-term prognosis of this understudied patient population and may discover new genetic background underlying the disease mechanism and provide potential targets for drug development.

Conditions

Trial Design

  • Observation: Case Control
  • Perspective: Prospective
  • Sampling: Probability Sample

Trial Population

1. Patients aged 18 to 49 hospitalized due to first-ever imaging-positive ischemic stroke of undetermined etiology; 2. Age-, gender- and race-ethnicity-matched stroke-free control subjects

Outcomes

Type Measure Time Frame Safety Issue
Primary Nonfatal or fatal recurrent ischemic stroke 10 years No
Secondary Composite of noncerebrovascular arterial or venous thrombotic events, or cerebral venous thrombosis 10 years No
Secondary Death from any cause 10 years No
Secondary New-onset atrial fibrillation 10 years No

Biospecimen Retention:Samples With DNA - Patients at baseline: 4 x 2.7 mL sodium citrate tube, aliquoted in 10 x 300 µL cryovials; 1 x 5 mL PPACK sodium citrate tube, aliquoted in 5 x 300 µL cryovials; 1 x 8 mL serum tube, aliquoted in 5 x 300 µL cryovials; 1 x 9 mL EDTA tube #1, aliquoted in 10 x 300 µL cryovials; 1 x 9 mL EDTA tube #2, full blood for DNA extraction. Patients at 3-month visit (fasting): 4 x 2.7 mL sodium citrate tube, aliquoted in 10 x 300 µL cryovials; 1 x 5 mL PPACK sodium citrate tube, aliquoted in 5 x 300 µL cryovials; 1 x 8 mL serum tube, aliquoted in 5 x 300 µL cryovials; 1 x 9 mL EDTA tube, aliquoted in 10 x 300 µL cryovials. Control subjects: 4 x 2.7 mL sodium citrate tube, aliquoted in 10 x 300 µL cryovials; 1 x 5 mL PPACK sodium citrate tube, aliquoted in 5 x 300 µL cryovials; 1 x 8 mL serum tube, aliquoted in 5 x 300 µL cryovials; 1 x 9 mL EDTA tube #1, aliquoted in 10 x 300 µL cryovials; 1 x 9 mL EDTA tube #2, full blood for DNA extraction.

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