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

Ischemic Stroke Clinical Trial

— SECRETO  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01934725
• Other study ID #: SECRETO
• Status: Recruiting
• Start date: November 2013
• Est. completion date: December 2031

Study information

• Verified date: November 2023
• Source: SECRETO Study Consortium
• Contact: Jukka Putaala, A/Prof.
• Phone: +35894711
• Email: jukka.putaala[@]hus.fi
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1200
• Est. completion date: December 2031
• Est. primary completion date: December 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 49 Years

Eligibility

PATIENTS:

Inclusion Criteria:

1. Age 18 to 49 at stroke onset

2. Patient hospitalized due to first-ever imaging-positive ischemic stroke of undetermined etiology after complete timely diagnostic testing.

Exclusion Criteria:

1. Baseline mandatory tests not obtained in the first week following stroke onset, including:

• Brain MRI

• Routine blood tests, including complete blood count, CRP, fasting glucose, creatinine, aPTT, INR, total cholesterol, LDL-cholesterol, HDL-cholesterol, HbA1C, hemoglobin electrophoresis in individuals of African origin

2. Other baseline mandatory tests not obtained within the first two weeks following stroke onset, including:

• Imaging of cervicocephalic arteries by CTA, MRA, or DSA

• Transesophageal (highly recommended) or transthoracic echocardiography

• 24-hour Holter monitoring or continuous in-hospital ECG monitoring with automated arrhythmia detection for at least 24 hours

• Screening for thrombophilia, including antiphospholipid antibodies and other coagulopathies (any abnormal finding must be retested at mandatory 3-month follow-up visit >12 weeks from initial testing or >4 weeks after cessation of anticoagulation at any later time point); mandatory tests include anticardiolipin antibodies, lupus anticoagulant, anti-ß2-glycoprotein antibodies, factor V mutation (or aPC resistency ruled out), factor II mutation, homocysteine, antithrombin III, protein C, and protein S

3. No evidence of current brain ischemia

4. Current stroke due to cerebral venous thrombosis or as a complication of subarachnoid hemorrhage, angiography, or cardiac surgery

5. Patient otherwise not eligible for the study or adherent for follow-up (eg nonresident) or has concurrent disease affecting outcome (eg multiple sclerosis, cancer)

6. Informed consent not obtained from the patient or a proxy.

CONTROL SUBJECTS:

Inclusion Criteria:

1. Age 18 to 49 years

2. Absence of prior ischemic stroke as ascertained using the Questionnaire for Verifying Stroke-Free Status

Exclusion Criterion:

1. Informed consent not obtained

Related Conditions & MeSH terms

• Brain Infarction
• Foramen Ovale, Patent
• Infarction
• Ischemic Stroke
• Stroke
• Thrombosis

Locations

Country	Name	City	State
Estonia	Tartu University Hospital	Tartu
Finland	Helsinki University Central Hospital	Helsinki
Finland	Kuopio University Hospital	Kuopio
Finland	Oulu University Hospital	Oulu
Finland	Tampere University Hospital	Tampere
Finland	Turku University Central Hospital	Turku
Germany	Ernst-Moritz-Arndt University Medicine	Greifswald
Greece	"Attikon" Hospital, University of Athens, School of Medicine	Athens
Italy	University of Brescia	Brescia
Italy	Arcispedale S. Maria Nuova	Reggio Emilia
Lithuania	Vilnius University Hospital Santariskiu klinikos	Vilnius
Netherlands	Radboud University Nijmegen Medical Centre	Nijmegen
Norway	Haukeland University Hospital	Bergen
Portugal	Hospital Santa Maria	Lisboa
Spain	Torrecárdenas University Hospital	Almería
Sweden	Sahlgrenska University Hospital	Gothenburg
Turkey	Istanbul University Istanbul Faculty of Medecine	Istanbul
United Kingdom	Peterborough City Hospital	Peterborough
United Kingdom	Royal Stoke University Hospital	Stoke-on-Trent

Sponsors (9)

Lead Sponsor	Collaborator
SECRETO Study Consortium	Academy of Finland, Finnish Medical Foundation, Hospital District of Helsinki and Uusimaa, Hospital District of North Ostrobothnia, Hospital District of Southwestern Finland, Northern Savo Hospital District, Pirkanmaa Hospital District, Sahlgrenska University Hospital, Sweden

Countries where clinical trial is conducted

Estonia,  Finland,  Germany,  Greece,  Italy,  Lithuania,  Netherlands,  Norway,  Portugal,  Spain,  Sweden,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Modified Rankin Scale	Functional outcome will be assessed with modified Rankin Scale at mandatory 3-month visit and at annual follow-up contacts from year 1 to year 10.	10 years
Other	Vocational outcome	Vocational status will be assessed at each follow-up contact with Poststroke Working Activity Questionnaire and a set of questions designed for the study.	10 years
Other	Cognitive outcome	Cognition will be assessed at mandatory 3-month follow-up visit (Montreal Cognitive Assessment).	3 months
Other	Anxiety and depression	Poststroke anxiety and depression will be evaluated at 3-month visit, 1-year, 5-year, and 10-year follow-up contacts with Hospital Anxiety and Depression Scale.	10 years
Other	Quality of life	Quality of life will be assessed at 3-month visit, 1-year, 5-year, and 10-year follow-up contacts with EuroQol questionnaire.	10 years
Other	Caregiver burden	Poststroke burden to caregiver will be assessed at 3-month visit with Expanded Caregiver Strain Index Questionnaire.	3 months
Other	Barthel Index	Functional outcome will be assessed with Barthel Index at mandatory 3-month visit and at annual follow-up contacts from year 1 to year 10.	10 years
Primary	Nonfatal or fatal recurrent ischemic cerebrovascular event	Ischemic stroke or transient ischemic attack	10 years
Secondary	Composite of noncerebrovascular arterial or venous thrombotic events, or cerebral venous thrombosis		10 years
Secondary	Death from any cause		10 years
Secondary	New-onset atrial fibrillation		10 years

External Links

•   Study website