Clinical trial NCT00657969: Looking For Genetic and Environmental Risk Factors and Therapeutic Aspects in Cervical Artery Dissections
Official title: Looking For Genetic and Environmental Risk Factors and Therapeutic Aspects in Cervical Artery Dissections
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Cervical Artery Dissection
Stroke
Brain Infarction
Keywords: Polymorphism, genetic
Risk factors
Carotid Artery, Internal, Dissection
Vertebral Artery Dissection
Genetic predisposition
Outcome
Therapy
Lead sponsor: Cervical Artery Dissections and Ischemic Stroke Patients - Consortium
Sponsor class: NETWORK
First posted: 2008-04-14
Enrollment: 4169
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: groups 1 and 2: hospital-based, neurology departments group 3: community samples

Brief summary: The main purpose of this study is to look for genetic and environmental risk factors of cervical artery dissections, a major cause of ischemic stroke in young adults, in a large multicenter case-control trial

Detailed description: Background: Cervical artery dissections (CAD) are a major cause of ischemic stroke, longstanding disability, and occasionally death in young adults. Several lines of evidence suggest genetic predisposition for CAD. Previous genetic studies were, however, inconclusive mainly due to insufficient numbers of patients. Our hypothesis is that CAD is a multifactorial disease caused by yet largely unidentified genetic variants and environmental factors, which may interact.

Aim: Our main aim is to look for genetic and environmental risk factors and gene-environment interactions potentially underlying CAD. In addition, therapeutic aspects are addressed in the setting of a multicenter registry.

Methods: We organized a multinational European network, CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) which targets at increasing our knowledge on the pathophysiological mechanisms of this disease in a large, representative patient population. Within this network, we are aiming to perform a de novo genetic association analysis using both a genome-wide and a candidate gene approach. For this purpose, 1130 patients with CAD, 1130 patients with non-CAD ischemic stroke, and 1890 healthy controls are being recruited, and detailed clinical, laboratory, diagnostic, therapeutic and outcome data are being collected from all participating patients. We are expecting to reach the above numbers of subjects by the end of 2008. Analyses of the CADISP database might clarify a number of debated issues, including risk factors, stroke preventive treatment, and outcome predictors of CAD.

We present the strategy of a collaborative project searching for genetic risk factors of cervical artery dissections. We hope that the CADISP network will provide detailed and novel data on risk factors and treatment aspects of CAD.

Eligibility criteria: GROUP1:

Inclusion Criteria:

* Typical radiological aspect of dissection\* in a cervical artery (carotid and/or vertebral);\* Mural hematoma, pseudoaneurysm, long tapering stenosis, intimal flap, double lumen, or occlusion \> 2 cm above the carotid bifurcation revealing a pseudo aneurysm or a long tapering stenosis after recanalisation
* Written informed consent

Exclusion Criteria:

* Purely intracranial dissection
* Dissection occurring after an endovascular procedure
* Known mendelian genetic disorder that can explain the dissection (e.g. vascular Ehlers-Danlos syndrome)

GROUP2:

Inclusion Criteria:

* Recent ischemic stroke
* No signs of CAD on extracranial duplex sonography and angiography (digital subtraction or magnetic resonance or CT), performed \< 7 days after the stroke
* Written informed consent

Exclusion Criteria:

* Possible cerebral ischemia but normal cerebral imaging
* CAD cannot be ruled out (e.g.persistent arterial occlusion without mural hematoma)
* Endovascular or surgical procedure on the coronary, cervical or cerebral arteries during the 48 hours preceding the cerebral infarction
* Cardiopathies with a very high embolic risk (Mechanical prosthetic valves, mitral stenosis with atrial fibrillation, intracardiac tumor, infectious endocarditis, myocardial infarction\<4 months)
* Arterial vasospasm following a subarachnoid haemorrhage
* Auto-immune disease possibly responsible for the cerebral infarction
* Known monogenic disease responsible for the cerebral infarction

GROUP3:

Inclusion criteria:

* Individuals from the general population without history of stroke, dissections in any artery, transient ischemic attack, coronary artery disease, peripheral artery disease
* Written informed consent

Primary outcomes:
measure: association of genetic polymorphisms with cervical artery dissections
timeFrame: 2009
Secondary outcomes:
measure: association of environmental risk factors with cervical artery dissections
timeFrame: 2009
measure: gene-environment interactions
timeFrame: 2009
Other outcomes:
Locations:
city: Cordoba
country: Argentina
facility: Sanatorio Allende
city: Brussels
country: Belgium
facility: Department of Neurology, University Hospital of Brussels (ULB)
city: Leuven
country: Belgium
facility: Department of Neurology, University Hospital of Leuven
city: Helsinki
country: Finland
facility: Department of Neurology, Helsinki University Central Hospital
city: Amiens
country: France
facility: Department of Neurology, University Hospital of Amiens
city: Besançon
country: France
facility: Department of Neurology, University Hospital of Besançon
city: Dijon
country: France
facility: Department of Neurology, University Hospital of Dijon
city: Lille
country: France
facility: Department of Neurology, University Hospital of Lille
city: Lille
country: France
facility: Inserm U744 Institut Pasteur de Lille
city: Paris
country: France
facility: Department of Neurology, University Hospital Pitié-Salpêtrière
city: Paris
country: France
facility: Department of Neurology, University Hospital Sainte-Anne
city: Heidelberg
country: Germany
facility: Rehabilitation Center, Schmieder-Klinik
city: Heidelberg
country: Germany
facility: Department of Neurology, University Hospital of Heidelberg
city: Ludwigshafen
country: Germany
facility: Department of Neurology, Hospital of Ludwigshafen
city: Munich
country: Germany
facility: Department of Neurology, University Hospital of Munich
city: Brescia
country: Italy
facility: Department of Neurology, University Hospital of Brescia
city: Milano
country: Italy
facility: Department of Neurology, Ospedale Maggiore Policlinico di Milano
city: Milano
country: Italy
facility: Ospedale Milano San Raffaele
city: Monza
country: Italy
facility: Department of Neurology, University Hospital Milano-Bicocca
city: Perugia
country: Italy
facility: Department of Neurology, University Hospital of Perugia
city: Rome
country: Italy
facility: Rehabilitation Center, IRCCS Santa Lucia, Roma
city: Basel
country: Switzerland
facility: Department of Neurology, University Hospital of Basel
city: Istanbul
country: Turkey
facility: Department of Neurology, Cerrahpasa Medical Faculty, Istanbul University
city: London
country: United Kingdom
facility: Department of Neuroscience, St George's University Hospital of London
Study officials:
affiliation: Department of Neurology (EA2691), University Hospital of Lille; Inserm, U744, Pasteur Institute, Lille, France
name: Stéphanie Debette, MD, PhD
role: STUDY_DIRECTOR
affiliation: Department of Neurology, University Hospital of Heidelberg, Germany
name: Caspar Grond-Ginsbach, PhD
role: STUDY_CHAIR
affiliation: Department of Neurology (EA2691), University Hospital of Lille, France
name: Didier Leys, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Engelter ST, Brandt T, Debette S, Caso V, Lichy C, Pezzini A, Abboud S, Bersano A, Dittrich R, Grond-Ginsbach C, Hausser I, Kloss M, Grau AJ, Tatlisumak T, Leys D, Lyrer PA; Cervical Artery Dissection in Ischemic Stroke Patients (CADISP) Study Group. Antiplatelets versus anticoagulation in cervical artery dissection. Stroke. 2007 Sep;38(9):2605-11. doi: 10.1161/STROKEAHA.107.489666. Epub 2007 Jul 26.
citation: Debette S, Metso TM, Pezzini A, Engelter ST, Leys D, Lyrer P, Metso AJ, Brandt T, Kloss M, Lichy C, Hausser I, Touze E, Markus HS, Abboud S, Caso V, Bersano A, Grau A, Altintas A, Amouyel P, Tatlisumak T, Dallongeville J, Grond-Ginsbach C; CADISP-group. CADISP-genetics: an International project searching for genetic risk factors of cervical artery dissections. Int J Stroke. 2009 Jun;4(3):224-30. doi: 10.1111/j.1747-4949.2009.00281.x.