Biocollection on the Familial Forms of Intracranial Aneurysm

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Intracranial Aneurysm Aneurysm Brain Diseases Cardiovascular Diseases Central Nervous System Diseases Cerebrovascular Disorders Intracranial Arterial Diseases Nervous System Diseases Vascular Diseases

Age range

20 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

AP-HP, Henri Mondor hospital, Créteil, France

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Non-Interventional

Genetic

Primary outcomes

DNA analysis to identify new genes (and new physiological pathways) associated to the risk of intracranial aneurysm

Time frame: Until one year

Sponsors and collaborators

Lead sponsor

Nantes University Hospital

Other

Registry information

Official study title

Genetic Study on the Familial Forms of Intracranial Aneurysm

Acronym: GAÏA

Important dates

Study start: 2013
Primary completion: 2017
Study completion: 2017
First posted: Jul 28, 2016
Registry last updated: Aug 11, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Completed