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Biocollection on the Familial Forms of Intracranial Aneurysm (GAÏA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02848495
Recruitment Status : Completed
First Posted : July 28, 2016
Last Update Posted : August 11, 2017
Information provided by (Responsible Party):
Nantes University Hospital

Brief Summary:

Intracranial aneurysm (IA) is an asymptomatic cerebrovascular abnormality affecting 3.2% of the general population. The devastating complication of IA is its rupture, resulting in subarachnoid haemorrhage that can lead to severe disability and death.

Unfortunately, there are neither reliable clues nor diagnostic tools to predict the formation and/or the fate of an IA in a given individual. Also, there is no pharmacological drug available to prevent the rupture of aneurysm and subsequent subarachnoid haemorrhage. Current treatments are invasive with a significant risk of procedural morbidity. Thus, still now, the management of patients with IA remains extremely challenging and still controversial.

Although the pathogenesis of IA has been the subject of many studies for the last decade, the mechanisms underlying IA formation, growth and rupture are still mostly unknown and relevant animal models of IA are not available.

Familial history of IA predisposes to IA formation and rupture and increasing evidence suggest a genetic component of IA formation, with heterogeneous modes of inheritance and penetrance.

This project, gathering neuroradiologists, geneticists and vascular biologists, addresses the urgent need to understand the pathogenic mechanisms of IA to develop diagnostic and predictive tools of risk of IA.

The investigators propose to identify IA-causing variants by whole-exome sequencing in familial forms of the disease.

The investigators hypothesises that the functional analysis of the causal / susceptibility variants thus identified will provide clues to understanding the pathological mechanisms of IA formation, and the bases for developing diagnostic tools. This project aims at meeting this challenge. Based on preliminary data that already allowed to identify such a variant, and the combination of genetic and functional investigations, the specific objectives of this project are: - To identify IA-causing variants in familial forms of the disease by whole-exome sequencing; - To understand the function of these genes/ variants in the formation and rupture of IA by molecular and cellular approaches and generation of relevant animal models; - To discover potential biomarkers of risk of IA formation and/or rupture.

Condition or disease Intervention/treatment
Intracranial Aneurysm Genetic: Non-Interventional

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Study Type : Observational
Actual Enrollment : 411 participants
Observational Model: Family-Based
Time Perspective: Prospective
Official Title: Genetic Study on the Familial Forms of Intracranial Aneurysm
Actual Study Start Date : January 2013
Actual Primary Completion Date : January 2017
Actual Study Completion Date : January 2017

Resource links provided by the National Library of Medicine

Primary Outcome Measures :
  1. DNA analysis to identify new genes (and new physiological pathways) associated to the risk of intracranial aneurysm [ Time Frame: Until one year ]

Biospecimen Retention:   Samples With DNA
For one patient included: Ethylenediaminetetraacetic acid (EDTA) tubes for DNA (20 mL blood)

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

The initial stage of this biocollection based on the recruitment of large families for genetic linkage analysis.

In the first instance, we identify patients with intracranial aneurysms occurring in a family context, and to conduct a comprehensive investigation according to clinical guidelines in force to assess the potentially informative family and ensure their adherence to the prior biocollection. The next step consists on the fine and accurate phenotyping of each of the family members (imaging) and the collection of a blood sample for DNA extraction for molecular genetic analysis.

The population recruited will be composed of index and their healthy relatives and cases with sporadic cases and IA. The kinship links will be established from family trees.


Inclusion criteria :

  • Inclusion criteria indexes and related cases (familial) of intracranial aneurysms:

    • Index: Any patient consulting for a major IA and some typical bifurcation with at least one other case reached akin IA 1st degree
    • Related: All similar to the first degree, aged 20 or more, patients with a family background of IA and some typical bifurcation (≥2 achieved) For the latter, directed by screening with Magnetic resonance imaging (MRI) sequence Time of Flight (TOF), axial T2, EGT2.
    • Consent oral and in writing to the Biocollection consent Form for participation in the collection of biological samples
  • Inclusion criteria sporadic cases of IA:

    • Any patient consulting for IA and some typical bifurcation
    • Patients aged of 20 years or older
    • Consent oral and in writing to the Biocollection consent Form for participation in the collection of biological samples

Exclusion Criteria :

- Non Inclusion Criteria:

  • Patients who have shown the inability or have refused to sign the consent informed biocollection
  • Syndromic diagnosis known as IA provider
  • Marfan Syndrome
  • AOS with SMAD 3
  • Danlos Syndrome Elhers type II and IV
  • Autosomal Dominant Polycystic
  • Moyamoya Syndrome
  • Character of IA:
  • Dissecting or fusiform
  • Combined with an arteriovenous malformation
  • Blister-like
  • Mycotic
  • Pathology of the cerebral white matter detected on MRI, evoking:
  • COL4A1 mutation

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02848495

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AP-HP, Henri Mondor hospital
Créteil, France, 94000
CHD La Roche sur YON
La Roche sur YON, France, 85925
Nantes University Hospital
Nantes, France, 44093
University Hospital Poitiers
Poitiers, France, 86021
University Hospital Rennes
Rennes, France, 35033
Rouen University Hospital
Rouen, France, 76031
Bordeaux University Hospital
Talence, France, 33404
Tours University Hospital
Tours, France, 37044
Sponsors and Collaborators
Nantes University Hospital
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Principal Investigator: Romain BOURCIER, PhD Nantes University Hospital

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Nantes University Hospital Identifier: NCT02848495     History of Changes
Other Study ID Numbers: RC12_0458
First Posted: July 28, 2016    Key Record Dates
Last Update Posted: August 11, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Nantes University Hospital:
Familial Form
Additional relevant MeSH terms:
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Intracranial Aneurysm
Vascular Diseases
Cardiovascular Diseases
Intracranial Arterial Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases