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Brain InfarctionSECRETONCT01934725

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

An observational study of Brain Infarction and Ischemic Stroke, run by SECRETO Study Consortium at 19 sites in 13 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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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. Read more about this study

Who is it for?
Ages 18 to 49 yearsHealthy volunteers can take part
Conditions the study is for
Brain Infarction, Ischemic Stroke, Thrombosis
How many people
1,200 participants
Where
19 sitesin 13 countries
Study dates
Nov 2013to Dec 2031
Phase
Observational
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 49 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Study 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

Who may be able to join

  • Age 18 to 49 at stroke onset
  • Patient hospitalized due to first-ever imaging-positive ischemic stroke of undetermined etiology after complete timely diagnostic testing.
  • Age 18 to 49 years
  • Absence of prior ischemic stroke as ascertained using the Questionnaire for Verifying Stroke-Free Status

Who cannot join

  • 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
  • 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
Show all 14Show fewer
  • 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-β2-glycoprotein antibodies, factor V mutation (or aPC resistency ruled out), factor II mutation, homocysteine, antithrombin III, protein C, and protein S
  • No evidence of current brain ischemia
  • Current stroke due to cerebral venous thrombosis or as a complication of subarachnoid hemorrhage, angiography, or cardiac surgery
  • Patient otherwise not eligible for the study or adherent for follow-up (eg nonresident) or has concurrent disease affecting outcome (eg multiple sclerosis, cancer)
  • Informed consent not obtained from the patient or a proxy.
  • CONTROL SUBJECTS:
  • 1. Informed consent not obtained

Trial locations and contacts

19 sites in 13 countries.

19 sites in 13 countries

Finland5 sites

  • Helsinki University Central Hospital

    Helsinki, FI-00029

  • Kuopio University Hospital

    Kuopio, 70029

  • Oulu University Hospital

    Oulu

  • Tampere University Hospital

    Tampere

  • Turku University Central Hospital

    Turku

Other trials in Finland

Italy2 sites

  • University of Brescia

    Brescia, 25123

  • Arcispedale S. Maria Nuova

    Reggio Emilia

Other trials in Italy

United Kingdom2 sites

  • Peterborough City Hospital

    Peterborough

  • Royal Stoke University Hospital

    Stoke-on-Trent

Other trials in United Kingdom

Estonia1 site

  • Tartu University Hospital

    Tartu

Other trials in Estonia

Germany1 site

  • Ernst-Moritz-Arndt University Medicine

    Greifswald

Other trials in Germany

Greece1 site

  • "Attikon" Hospital, University of Athens, School of Medicine

    Athens

Other trials in Greece

Lithuania1 site

  • Vilnius University Hospital Santariskiu klinikos

    Vilnius

Other trials in Lithuania

Netherlands1 site

  • Radboud University Nijmegen Medical Centre

    Nijmegen, 6500 HB

Other trials in Netherlands

Norway1 site

  • Haukeland University Hospital

    Bergen, 5021

Other trials in Norway

Portugal1 site

  • Hospital Santa Maria

    Lisbon, 1649-035

Other trials in Portugal

Spain1 site

  • Torrecárdenas University Hospital

    Almería

Other trials in Spain

Sweden1 site

  • Sahlgrenska University Hospital

    Gothenburg

Other trials in Sweden

Turkey (Türkiye)1 site

  • Istanbul University Istanbul Faculty of Medecine

    Istanbul

Other trials in Turkey (Türkiye)

About this study

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

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.

Read more

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.

Keywords
Ischemic Stroke, Brain Infarction, Patent Foramen Ovale, Stroke in the Young, Myocardial Infarction, Cerebral Venous Thrombosis, Pulmonary Embolism, Deep Vein Thrombosis, Subarachnoid Hemorrhage, Prognosis, Databases, Genetic
Medical subject headings
Brain Infarction, Ischemic Stroke, Thrombosis, Foramen Ovale, Patent, Myocardial Infarction, Intracranial Thrombosis, Pulmonary Embolism, Venous Thrombosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT01934725
Study groupRoleWhat they receive
Patients w/ cryptogenic ischemic strokePatients aged 15 to 49 years with unexplained first-ever ischemic stroke
Stroke-free control subjectsStroke-free subjects age- and gender-matched to patients

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Nonfatal or fatal recurrent ischemic cerebrovascular event

    Ischemic stroke or transient ischemic attack

    Measured: 10 years

Secondary outcomes (3)

  1. Composite of noncerebrovascular arterial or venous thrombotic events, or cerebral venous thrombosis

    Measured: 10 years

  2. Death from any cause

    Measured: 10 years

  3. New-onset atrial fibrillation

    Measured: 10 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Sep 2013 (estimated)
  2. Study startNov 2013
  3. Primary completionDec 2031 (estimated)
  4. Study completionDec 2031 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Case-control
Time perspective
Prospective
Enrolment
1,200 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01934725
Sponsor's protocol ID
SECRETO
Acronym
SECRETO
Status last verified
May 2025
First submitted
29 Aug 2013
Last updated
16 May 2025
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Undecided

Publications

  • Valanciene J, Ylikotila P, Lautamaki R, Zedde M, Grimaldi T, Sarkanen T, Ryodi E, Jatuzis D, Ryliskiene K, Zakarkaite D, von Sarnowski B, Busch R, Tulkki L, Pirinen J, Martinez-Majander N, Licenik R, Ferdinand P, Oxley C, Korv J, Muda P, Helin TA, Joutsi-Korhonen L, Szanto T, Pezzini A, Lombardi CM, Tsivgoulis G, Suihko S, Tolppanen H, Fonseca AC, Martinez-Sanchez P, Amaya-Pascasio L, Abels S, de Leeuw FE, Yesilot N, Sezgin M, Waje-Andreassen U, Saeed S, Redfors P, Bech-Hanssen O, Huhtakangas J, Hedman M, Jakala P, Ten Cate H, Gerdts E, Lehto M, Sinisalo J, Putaala J; SECRETO Study Group Investigators. Association Between Recent Mechanical Risk Factors for Venous Thrombosis and Young-Onset Cryptogenic Ischemic Stroke. Stroke. 2026 Aug 26. doi: 10.1161/STROKEAHA.125.054299. Online ahead of print.

    PubMed 42644242

  • Dong A, Paju S, Leskela J, Manzoor M, Putaala J, Ylikotila P, Kononen E, Pussinen P, Zaric S. Microbial burden of periodontal diseases and its clinical application: The stage, grade, and furcation matter. J Periodontol. 2026 May 17. doi: 10.1002/jper.70140. Online ahead of print.

    PubMed 42143599

  • Hulsen BM, Spiegelenberg JP, Martinez-Majander N, Tulkki L, Sarkanen T, Jakala P, Redfors P, Huhtakangas J, Ylikotila P, von Sarnowski B, Yesilot N, Waje-Andreassen U, Fonseca AC, Martinez-Sanchez P, Korv J, Ferdinand P, Ryliskiene K, Pezzini A, Licenik R, Zedde M, Sinisalo J, Gerdts E, Helin TA, Joutsi-Korhonen L, Szanto T, Palm F, Grau AJ, de Leeuw FE, Putaala J. Preceding Infections and Coagulation Biomarkers in Early-Onset Cryptogenic Ischemic Stroke. Stroke. 2026 May;57(5):1220-1230. doi: 10.1161/STROKEAHA.125.052134. Epub 2026 Mar 17.

    PubMed 41841261

  • Sihvo MC, Ylikotila P, Zedde M, Pascarella R, Sarkanen T, Jatuzis D, Ryliskiene K, von Sarnowski B, Licenik R, Ferdinand P, Korv J, Korv L, Pezzini A, Fonseca AC, Paula A, Martinez-Sanchez P, Yesilot N, Fromm A, Waje-Andreassen U, Redfors P, Jood K, Huhtakangas J, Sairanen T, Hedman M, Jakala P, Ten Cate H, Gerdts E, Lehto M, Sinisalo J, Kittner SJ, Mitchell BD, Lindgren AG, Ilinca A, Putaala J, Tomppo L. Family history of stroke and cardiovascular diseases in early-onset cryptogenic ischaemic stroke. Eur Stroke J. 2026 Mar 1;11(3):aakag013. doi: 10.1093/esj/aakag013.

    PubMed 41792039

  • Kakaletsis N, Gordin D, Martinez-Majander N, Joutsi-Korhonen L, Salopuro T, Adeshara K, Sibolt G, Curtze S, Pirinen J, Soinne L, Sairanen T, Suihko S, Lehto M, Sinisalo J, Tatlisumak T, Groop PH, Putaala J. Insights into the vascular aging burden in young adults with embolic stroke of undetermined source. J Neurol Sci. 2025 Sep 15;476:123642. doi: 10.1016/j.jns.2025.123642. Epub 2025 Jul 28.

    PubMed 40743598

  • Putaala J, Martinez-Majander N, Leppert M, Tulkki L, Pirinen J, Tolppanen H, Sarkanen T, Virtanen M, Jaakonmaki N, Jakala P, Hedman M, Redfors P, Bech-Hanssen O, Junttola U, Huhtakangas J, Ylikotila P, Lautamaki R, Schminke U, von Sarnowski B, Busch R, Yesilot N, Sezgin M, Waje-Andreassen U, Saeed S, Fonseca AC, Paula A, Amaya Pascasio L, Martinez-Sanchez P, Korv J, Muda P, Ferdinand P, Oxley C, Zakarkaite D, Ryliskiene K, Pezzini A, Lombardi CM, Licenik R, Zedde M, Grimaldi T, Tsivgoulis G, Sinisalo J, Gerdts E, Tatlisumak T; SECRETO Study Group. Burden of Modifiable Risk Factors in Young-Onset Cryptogenic Ischemic Stroke by High-Risk Patent Foramen Ovale. Stroke. 2025 Jun;56(6):1428-1440. doi: 10.1161/STROKEAHA.124.049855. Epub 2025 Apr 17.

    PubMed 40242852

  • Kutal S, Tulkki LJ, Sarkanen T, Redfors P, Jood K, Nordanstig A, Yesilot N, Sezgin M, Ylikotila P, Zedde M, Junttola U, Fromm A, Ryliskiene K, Licenik R, Ferdinand P, Jatuzis D, Korv L, Korv J, Pezzini A, Sinisalo J, Lehto M, Gerdts E, Autere J, Fonseca AC, Waje-Andreassen U, Von Sarnowski B, Sairanen T, Tatlisumak T, Huhtakangas J, Jakala P, Putaala J, Martinez-Majander N. Association Between Self-Perceived Stress and Cryptogenic Ischemic Stroke in Young Adults: A Case-Control Study. Neurology. 2025 Mar 25;104(6):e213369. doi: 10.1212/WNL.0000000000213369. Epub 2025 Mar 5.

    PubMed 40043226

  • Sindre RB, Gerdts E, Putaala J, Grymyr LMD, Midtbo H, Almeida AG, Bech-Hanssen O, Busch R, Eilertsen RK, Fonseca AC, Hedman M, Huhtakangas J, Jakala P, Lautamaki R, Lehto M, Martinez-Majander N, Redfors P, Sarkanen T, von Sarnowski B, Sinisalo J, Virtanen M, Waje-Andreassen U, Yesilot N, Ylikotila P, Cramariuc D. Association of Left Atrial Stiffness With Risk of Cryptogenic Ischemic Stroke in Young Adults. JACC Adv. 2024 Mar 14;3(4):100903. doi: 10.1016/j.jacadv.2024.100903. eCollection 2024 Apr.

    PubMed 38939654

  • Zedde M, Grisendi I, Assenza F, Napoli M, Moratti C, Bonacini L, Di Cecco G, D'Aniello S, Pavone C, Merlino G, Putaala J, Valzania F, Pascarella R. The Prepetrous Segment of the Internal Carotid Artery as a Neglected Site of Symptomatic Atherosclerosis: A Single-Center Series. J Clin Med. 2024 Mar 15;13(6):1696. doi: 10.3390/jcm13061696.

    PubMed 38541922

  • Tulkki L, Martinez-Majander N, Haapalahti P, Tolppanen H, Sinisalo J, Repo O, Sarkanen T, Numminen H, Ryodi E, Ylikotila P, Roine RO, Lautamaki R, Saraste A, Miettinen T, Autere J, Jakala P, Hedman M, Huhtakangas J, Junttola U, Putaala J, Pirinen J; SECRETO Study Group. 24-hour ambulatory blood pressure and cryptogenic ischemic stroke in young adults. Ann Med. 2023 Dec;55(1):2203513. doi: 10.1080/07853890.2023.2203513.

    PubMed 37086083

  • Kuusisto JK, Poyhonen PAK, Pirinen J, Lehmonen LJ, Raty HP, Martinez-Majander N, Putaala J, Sinisalo J, Jarvinen V. Revisiting left atrial volumetry by magnetic resonance imaging: the role of atrial shape and 3D angle between left ventricular and left atrial axis. BMC Med Imaging. 2021 Nov 9;21(1):167. doi: 10.1186/s12880-021-00701-5.

    PubMed 34753444

  • Poyhonen P, Kuusisto J, Pirinen J, Raty H, Lehmonen L, Paakkanen R, Martinez-Majander N, Gerdts E, Putaala J, Sinisalo J, Jarvinen V. Right atrium and cryptogenic ischaemic stroke in the young: a case-control study. Open Heart. 2021 May;8(1):e001596. doi: 10.1136/openhrt-2021-001596.

    PubMed 34006504

  • Poyhonen P, Kuusisto J, Jarvinen V, Pirinen J, Raty H, Lehmonen L, Paakkanen R, Martinez-Majander N, Putaala J, Sinisalo J. Left ventricular non-compaction as a potential source for cryptogenic ischemic stroke in the young: A case-control study. PLoS One. 2020 Aug 14;15(8):e0237228. doi: 10.1371/journal.pone.0237228. eCollection 2020.

    PubMed 32797064

  • Pirinen J, Jarvinen V, Martinez-Majander N, Sinisalo J, Poyhonen P, Putaala J. Left Atrial Dynamics Is Altered in Young Adults With Cryptogenic Ischemic Stroke: A Case-Control Study Utilizing Advanced Echocardiography. J Am Heart Assoc. 2020 Apr 7;9(7):e014578. doi: 10.1161/JAHA.119.014578. Epub 2020 Mar 25.

    PubMed 32208831

  • Martinez Majander N, Sinisalo J, Sundararajan S, Strbian D, Putaala J. Cryptic Loss of Consciousness in a 36-Year-Old Woman. Stroke. 2015 Jul;46(7):e164-6. doi: 10.1161/STROKEAHA.115.009405. Epub 2015 May 12. No abstract available.

    PubMed 25967578

Questions about this trial

What is this clinical trial studying?

An observational study of Brain Infarction and Ischemic Stroke, run by SECRETO Study Consortium at 19 sites in 13 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 16 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in Finland, Italy, United Kingdom, Estonia, Germany and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Nonfatal or fatal recurrent ischemic cerebrovascular event (time frame: 10 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01934725, which also lists 15 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2025.

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