Biocollection on the Familial Forms of Intracranial Aneurysm (GAÏA)

August 9, 2017 updated by: Nantes University Hospital

Genetic Study 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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Actual)

411

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Créteil, France, 94000
        • AP-HP, Henri Mondor hospital
      • La Roche sur YON, France, 85925
        • CHD La Roche sur Yon
      • Nantes, France, 44093
        • Nantes University Hospital
      • Poitiers, France, 86021
        • University Hospital Poitiers
      • Rennes, France, 35033
        • University Hospital Rennes
      • Rouen, France, 76031
        • ROUEN university hospital
      • Talence, France, 33404
        • Bordeaux university hospital
      • Tours, France, 37044
        • Tours university Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
DNA analysis to identify new genes (and new physiological pathways) associated to the risk of intracranial aneurysm
Time Frame: Until one year
Until one year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Nantes University Hospital

Investigators

  • Principal Investigator: Romain BOURCIER, PhD, Nantes University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2013

Primary Completion (Actual)

January 1, 2017

Study Completion (Actual)

January 1, 2017

Study Registration Dates

First Submitted

July 21, 2016

First Submitted That Met QC Criteria

July 25, 2016

First Posted (Estimate)

July 28, 2016

Study Record Updates

Last Update Posted (Actual)

August 11, 2017

Last Update Submitted That Met QC Criteria

August 9, 2017

Last Verified

August 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RC12_0458

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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