Stroke in Young Fabry Patients (sifap1): Frequency of Fabry Disease in Young Stroke Patients

NCT00414583 | Completed DMC

• 1 other identifier: II PV03/2006
• Study Type: observational
• Target: 5,000
• Locations: 14 countries
• Sites: 45

Brief Summary

More than one million people in Europe suffer from a stroke every day. Normally older people have a stroke, but also a significant number of younger people between 18 and 55 years. Usually, these cannot be explained by the classical risk factors such as diabetes, overweight and high blood pressure. New studies indicate that in about 1 - 2 % of the younger stroke patients the cause could have been an undiagnosed genetic disease, the so called Fabry disease. The purpose of this study is to determine in a large number of young stroke patients, how many strokes were caused by Fabry Disease.

Conditions

Cerebrovascular Accident

Keywords

Cerebrovascular Accident; Cerebrovascular Accident, Acute; CVA (Cerebrovascular Accident); Cerebral Stroke; Stroke, Acute; Cerebrovascular Stroke; Fabry Disease; Anderson-Fabry Disease; Fabry's Disease

Outcome Measures

Primary Outcomes (1)

• Prevalence of Fabry disease in the unselected group of young stroke patients

  baseline

Secondary Outcomes (1)

• Classification of stroke subtype in patients identified to have Fabry disease acc. to TOAST criteria, modified Rankin scale, Barthel index and MRI criteria.

  baseline

Study Arms (1)

Observation

all adult patients (18 - 55 years of age) with an acute cerebrovascular event of any etiology

Other: No intervention

Interventions

No intervention OTHER

Observational study, only laboratory analysis and diagnostic interventions done; no drug tested

Also known as: only 1 observational group

Observation

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Adult patients (18 - 55 years of age) with an acute cerebrovascular event of any etiology defined as patients having an acute ischemic stroke or transient ischemic attack less than 3 months before enrollment into the study

You may qualify if:

• Adult patients (18 - 55 years of age) with an acute cerebrovascular event of any etiology defined as patients having an acute ischemic stroke or transient ischemic attack less than 3 months before enrollment into the study
• MRI-scan evidence of associated corresponding brain infarction or hemorrhage, regardless of the duration of symptoms. Alternatively also patients with no signs of stroke in the MRI can be included if a stroke-experienced neurologist has done the initial diagnosis as ischemic stroke, transient ischemic attack or hemorrhage.
• Detailed MRI documentation at admission to entry to the study
• Diagnostic procedures for CVE according to the EUSI recommendations
• Written informed consent from patient or legal representative according to local regulations

You may not qualify if:

• Patients being younger than 18 years or older than 55 years of age.
• Acute ischemic stroke or transient ischemic attack longer than 3 months before enrolment into the study
• Diagnosis of the CVE within the last 3 months has been done by a non-neurologist if there is no MRI-scan evidence of associated brain infarction or hemorrhage
• No detailed MRI documentation at admission to entry to the study

Sponsors & Collaborators

• CENTOGENE GmbH Rostock: lead
• Shire Human Genetic Therapies, Inc.: collaborator

Study Sites (45)

Universitätsklinikum für Neurologie

Graz, A-8036, Austria

Location

Department of Neurology, Universitaetsklinik fuer Neurologie Innsbruck

Innsbruck, 6020, Austria

Location

Wagner-Jauregg Linz, Department of Neurology

Linz, A-4020, Austria

Location

Christian-Doppler-Klinik, Department für medizin. Studien

Salzburg, 5020, Austria

Location

Krankenhaus der Barmherzigen Brüder, Abteilung für Neurologie

Vienna, 1020, Austria

Location

Middelheim General Hospital, Dept. of Neurology/Memory Clinic

Antwerp, 2020, Belgium

Location

UZ Gasthuisburg Hospital

Leuven, 3000, Belgium

Location

Department of Neurology, University Hospital Sestre Milosrdnice

Zagreb, 10000, Croatia

Location

Helsinki University Central Hospital, Department of Neurology

Helsinki, 00290, Finland

Location

Hopital Neurologique de Lyon, Service d'urgences Neurovasculaires

Lyon, F-69003, France

Location

Department of Neurology, S. Khechinashvili University clinic of Tbilisi state medical university

Tbilisi, 0179, Georgia

Location

Department of Neurology, Kreiskrankenhaus Altenburg

Altenburg, 04600, Germany

Location

Department of Neurology, Klinikum Hohe Warte

Bayreuth, 95445, Germany

Location

Dept. of Neurology, Vivantes Netzwerk für Gesundheit GmbH, Klinikum Neukölln

Berlin, 12351, Germany

Location

Charite Campus Benjamin Franklin, Dept. of Neurology

Berlin, D-12200, Germany

Location

Klinikum Bremen Mitte gGmbH, Neurologische Klinik

Bremen, 28177, Germany

Location

Department of Neurology, Allgemeines Krankenhaus Celle

Celle, 29223, Germany

Location

Department of Neurology, Klinikum Chemnitz gGmbH

Chemnitz, 09131, Germany

Location

Department of Neurology, Universitaetsklinikum Carl Gustav Carus

Dresden, 01307, Germany

Location

Heinrich-Heine University Duesseldorf, Dept. of Neurology

Düsseldorf, D-40225, Germany

Location

Dept. of Neurology, Johann-Wolfgang-Goethe-Universität

Frankfurt, 60528, Germany

Location

University of Giessen-Marburg Dept. of Neurology

Giessen, D-35385, Germany

Location

Department of Neurology, Ernst-Moritz-Arndt-University

Greifswald, 17489, Germany

Location

Dept. of Neurology, Martin-Luther-Universität, Universitätsklinik und Poliklinik für Neurologie

Halle, 06120, Germany

Location

Department of Neurology S10, Universitaetsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

University of Heidelberg, Department of Neurology

Heidelberg, D-69120, Germany

Location

Department of Neurology, Universitaetsklinikum Jena

Jena, 07740, Germany

Location

University Schleswig-Holstein, Dept. of Neurology

Kiel, D-24105, Germany

Location

Department of Neurology, Universitaetsklinikum Leipzig

Leipzig, 04103, Germany

Location

Department of Neurology, Universitaetsklinikum Giessen und Marburg GmbH

Marburg, 35039, Germany

Location

Dept. of Neurology, Ökumenisches Hainich Klinikum gGmbH

Mühlhausen, 99974, Germany

Location

Ludwig-Maximilians-University of Munich, Dept. of Neurology

München, D-81377, Germany

Location

University of Muenster, Dept. of Neurology

Münster, D-48149, Germany

Location

Department of Neurology, Klinik und Poliklinik fuer Neurologie

Regensburg, 93053, Germany

Location

University of Rostock, Department of Neurology

Rostock, D-18055, Germany

Location

Department of Neurology, University Tuebingen

Tübingen, 72076, Germany

Location

University of Ulm, Department of Neurology

Ulm, D-89081, Germany

Location

The Adelaide and Meath Hospital, Department of Neurology

Dublin, 24, Ireland

Location

Dept. of Neurology, Ospoedale Maggiore Policlinico

Milan, 20122, Italy

Location

Neuromedical Ward, Mater Dei Hospital

Msida, Malta

Location

Institute of Psychiatry and Neurology, Dept. of Neurology

Warsaw, 02-957, Poland

Location

Centro Hospitalar de Lisboa Central, Servico de Neurologia

Lisbon, 1150-199, Portugal

Location

Department of Neurology, Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Stroke Prevention Research Unit, Dept. of Clinical Neurology, University of Glasgow, Southern General Hospital

Glasgow, Scotland, G51 4TF, United Kingdom

Location

Stroke Prevention Research Unit, John Radcliffe Hospital

Oxford, OX39DU, United Kingdom

Location

Related Publications (20)

• Rolfs A, Bottcher T, Zschiesche M, Morris P, Winchester B, Bauer P, Walter U, Mix E, Lohr M, Harzer K, Strauss U, Pahnke J, Grossmann A, Benecke R. Prevalence of Fabry disease in patients with cryptogenic stroke: a prospective study. Lancet. 2005 Nov 19;366(9499):1794-6. doi: 10.1016/S0140-6736(05)67635-0.

  PMID: 16298216 BACKGROUND

• Rolfs A, Martus P, Heuschmann PU, Grittner U, Holzhausen M, Tatlisumak T, Bottcher T, Fazekas F, Enzinger C, Ropele S, Schmidt R, Riess O, Norrving B; sifap1 Investigators. Protocol and methodology of the Stroke in Young Fabry Patients (sifap1) study: a prospective multicenter European study of 5,024 young stroke patients aged 18-55 years. Cerebrovasc Dis. 2011;31(3):253-62. doi: 10.1159/000322153. Epub 2010 Dec 21.

  PMID: 21178350 BACKGROUND

• Thijs V, Grittner U, Fazekas F, McCabe DJH, Giese AK, Kessler C, Martus P, Norrving B, Ringelstein EB, Schmidt R, Tanislav C, Putaala J, Tatlisumak T, von Sarnowski B, Rolfs A, Enzinger C; Stroke in Fabry (SIFAP1) Investigators. Dolichoectasia and Small Vessel Disease in Young Patients With Transient Ischemic Attack and Stroke. Stroke. 2017 Sep;48(9):2361-2367. doi: 10.1161/STROKEAHA.117.017406. Epub 2017 Jul 28.

  PMID: 28754833 DERIVED

• Aigner A, Grittner U, Rolfs A, Norrving B, Siegerink B, Busch MA. Contribution of Established Stroke Risk Factors to the Burden of Stroke in Young Adults. Stroke. 2017 Jul;48(7):1744-1751. doi: 10.1161/STROKEAHA.117.016599. Epub 2017 Jun 15.

  PMID: 28619986 DERIVED

• von Sarnowski B, Schminke U, Grittner U, Tanislav C, Bottcher T, Hennerici MG, Tatlisumak T, Putaala J, Kaps M, Fazekas F, Enzinger C, Rolfs A, Kessler C; sifap1 Investigators. Posterior versus Anterior Circulation Stroke in Young Adults: A Comparative Study of Stroke Aetiologies and Risk Factors in Stroke among Young Fabry Patients (sifap1). Cerebrovasc Dis. 2017;43(3-4):152-160. doi: 10.1159/000454840. Epub 2017 Jan 14.

  PMID: 28088807 DERIVED

• Huber R, Grittner U, Weidemann F, Thijs V, Tanislav C, Enzinger C, Fazekas F, Wolf M, Hennerici MG, McCabe DJ, Putaala J, Tatlisumak T, Kessler C, von Sarnowski B, Martus P, Kolodny E, Norrving B, Rolfs A; Stroke in Young Fabry Patients (SIFAP) Investigators. Patent Foramen Ovale and Cryptogenic Strokes in the Stroke in Young Fabry Patients Study. Stroke. 2017 Jan;48(1):30-35. doi: 10.1161/STROKEAHA.116.013620. Epub 2016 Nov 29.

  PMID: 27899752 DERIVED

• Tatlisumak T, Putaala J, Innila M, Enzinger C, Metso TM, Curtze S, von Sarnowski B, Amaral-Silva A, Jungehulsing GJ, Tanislav C, Thijs V, Rolfs A, Norrving B, Fazekas F, Suomalainen A, Kolodny EH. Frequency of MELAS main mutation in a phenotype-targeted young ischemic stroke patient population. J Neurol. 2016 Feb;263(2):257-262. doi: 10.1007/s00415-015-7969-z. Epub 2015 Nov 14.

  PMID: 26566914 DERIVED

• Wolf ME, Grittner U, Bottcher T, Norrving B, Rolfs A, Hennerici MG; sifap1 TM investigators. Phenotypic ASCO Characterisation of Young Patients with Ischemic Stroke in the Prospective Multicentre Observational sifap1 Study. Cerebrovasc Dis. 2015;40(3-4):129-35. doi: 10.1159/000434760. Epub 2015 Jul 25.

  PMID: 26227782 DERIVED

• Thijs V, Grittner U, Dichgans M, Enzinger C, Fazekas F, Giese AK, Kessler C, Kolodny E, Kropp P, Martus P, Norrving B, Ringelstein EB, Rothwell PM, Schmidt R, Tanislav C, Tatlisumak T, von Sarnowski B, Rolfs A; Stroke in Fabry Investigators. Family History in Young Patients With Stroke. Stroke. 2015 Jul;46(7):1975-8. doi: 10.1161/STROKEAHA.115.009341. Epub 2015 Jun 2.

  PMID: 26038521 DERIVED

• Fazekas F, Enzinger C, Schmidt R, Grittner U, Giese AK, Hennerici MG, Huber R, Jungehulsing GJ, Kaps M, Kessler C, Martus P, Putaala J, Ropele S, Tanislav C, Tatlisumak T, Thijs V, von Sarnowski B, Norrving B, Rolfs A; SIFAP 1 Investigators. Brain magnetic resonance imaging findings fail to suspect Fabry disease in young patients with an acute cerebrovascular event. Stroke. 2015 Jun;46(6):1548-53. doi: 10.1161/STROKEAHA.114.008548. Epub 2015 Apr 21.

  PMID: 25899239 DERIVED

• Tanislav C, Kropp P, Grittner U, Holzhausen M, Fazekas F, Jungehulsing GJ, Tatlisumak T, von Sarnowski B, Putaala J, Huber R, Thijs V, Schmidt R, Kaps M, Enzinger C, Dichgans M, Norrving B, Rolfs A. Clinically relevant depressive symptoms in young stroke patients - results of the sifap1 study. Neuroepidemiology. 2015;44(1):30-8. doi: 10.1159/000371389. Epub 2015 Jan 31.

  PMID: 25659436 DERIVED

• Kaps M, Grittner U, Jungehulsing G, Tatlisumak T, Kessler C, Schmidt R, Jukka P, Norrving B, Rolfs A, Tanislav C; sifap1 Investigators. Clinical signs in young patients with stroke related to FAST: results of the sifap1 study. BMJ Open. 2014 Nov 7;4(11):e005276. doi: 10.1136/bmjopen-2014-005276.

  PMID: 25380809 DERIVED

• Tanislav C, Grittner U, Misselwitz B, Jungehuelsing GJ, Enzinger C, von Sarnowski B, Putaala J, Kaps M, Kropp P, Rolfs A, Tatlisumak T, Fazekas F, Kolodny E, Norrving B. Lessons from everyday stroke care for clinical research and vice versa: comparison of a comprehensive and a research population of young stroke patients. BMC Neurol. 2014 Mar 7;14:45. doi: 10.1186/1471-2377-14-45.

  PMID: 24607068 DERIVED

• Fazekas F, Enzinger C, Schmidt R, Dichgans M, Gaertner B, Jungehulsing GJ, Hennerici MG, Heuschmann P, Holzhausen M, Kaps M, Kessler C, Martus P, Putaala J, Ropele S, Tanislav C, Tatlisumak T, Norrving B, Rolfs A; sifap1 Investigators. MRI in acute cerebral ischemia of the young: the Stroke in Young Fabry Patients (sifap1) Study. Neurology. 2013 Nov 26;81(22):1914-21. doi: 10.1212/01.wnl.0000436611.28210.ec. Epub 2013 Nov 1.

  PMID: 24186912 DERIVED

• Kropp P, Holzhausen M, Kolodny E, Becker U, Dichgans M, Diez-Tejedor E, Enzinger C, Fazekas F, Fuentes B, Karpinska A, Meyer W, Tanislav C, Bottcher T, Rolfs A; Stroke in Young Fabry Patients (sifap) Investigators. Headache as a symptom at stroke onset in 4,431 young ischaemic stroke patients. Results from the "Stroke in Young Fabry Patients (SIFAP1) study". J Neural Transm (Vienna). 2013 Oct;120(10):1433-40. doi: 10.1007/s00702-013-1014-0. Epub 2013 Jun 9.

  PMID: 23748977 DERIVED

• von Sarnowski B, Schminke U, Tatlisumak T, Putaala J, Grittner U, Kaps M, Tobin WO, Kinsella JA, McCabe DJ, Hennerici MG, Fazekas F, Norrving B, Kessler C, Rolfs A; sifap1 investigators. Prevalence of stenoses and occlusions of brain-supplying arteries in young stroke patients. Neurology. 2013 Apr 2;80(14):1287-94. doi: 10.1212/WNL.0b013e31828ab2ed. Epub 2013 Mar 6.

  PMID: 23468548 DERIVED

• Rolfs A, Fazekas F, Grittner U, Dichgans M, Martus P, Holzhausen M, Bottcher T, Heuschmann PU, Tatlisumak T, Tanislav C, Jungehulsing GJ, Giese AK, Putaala J, Huber R, Bodechtel U, Lichy C, Enzinger C, Schmidt R, Hennerici MG, Kaps M, Kessler C, Lackner K, Paschke E, Meyer W, Mascher H, Riess O, Kolodny E, Norrving B; Stroke in Young Fabry Patients (sifap) Investigators. Acute cerebrovascular disease in the young: the Stroke in Young Fabry Patients study. Stroke. 2013 Feb;44(2):340-9. doi: 10.1161/STROKEAHA.112.663708. Epub 2013 Jan 10.

  PMID: 23306324 DERIVED

• von Sarnowski B, Putaala J, Grittner U, Gaertner B, Schminke U, Curtze S, Huber R, Tanislav C, Lichy C, Demarin V, Basic-Kes V, Ringelstein EB, Neumann-Haefelin T, Enzinger C, Fazekas F, Rothwell PM, Dichgans M, Jungehulsing GJ, Heuschmann PU, Kaps M, Norrving B, Rolfs A, Kessler C, Tatlisumak T; sifap1 Investigators. Lifestyle risk factors for ischemic stroke and transient ischemic attack in young adults in the Stroke in Young Fabry Patients study. Stroke. 2013 Jan;44(1):119-25. doi: 10.1161/STROKEAHA.112.665190. Epub 2012 Nov 13.

  PMID: 23150649 DERIVED

• Steinicke R, Gaertner B, Grittner U, Schmidt W, Dichgans M, Heuschmann PU, Tanislav C, Putaala J, Kaps M, Endres M, Schmidt R, Fazekas F, Norrving B, Rolfs A, Martus P, Tatlisumak T, Enzinger C, Jungehulsing GJ. Kidney function and white matter disease in young stroke patients: analysis of the stroke in young fabry patients study population. Stroke. 2012 Sep;43(9):2382-8. doi: 10.1161/STROKEAHA.111.645713. Epub 2012 Jun 21.

  PMID: 22723456 DERIVED

• Fellgiebel A, Keller I, Martus P, Ropele S, Yakushev I, Bottcher T, Fazekas F, Rolfs A. Basilar artery diameter is a potential screening tool for Fabry disease in young stroke patients. Cerebrovasc Dis. 2011;31(3):294-9. doi: 10.1159/000322558. Epub 2010 Dec 22.

  PMID: 21196729 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Fabry diagnostic will be done centrally: blood samples will be retained for analysis of a-galactosidase in blood to diagnose an a-galactosidase deficit; in females direct analysis of the gene has to be done since due to the Lyonisation effect a-galactosidase activity might be normal in blood although the patient might suffer from Fabry disease.

MeSH Terms

Conditions

Stroke; Fabry Disease

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Cerebral Small Vessel Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2006
• First Posted: December 21, 2006
• Study Start: January 1, 2008
• Primary Completion: January 1, 2010
• Study Completion: January 1, 2010
• Last Updated: April 9, 2021

Record last verified: 2020-04

Locations

GE (1); BE (2); DE (26); MA (1); ES (1); IT (1); FI (1); CR (1); FR (1); GB (2); IE (1); AU (5); PT (1); PL (1)