Biocollection on the Familial Forms of Intracranial Aneurysm

Intracranial Aneurysm Clinical Trial

— GAÏA  

Official title:

Genetic Study on the Familial Forms of Intracranial Aneurysm

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02848495
• Other study ID #: RC12_0458
• Status: Completed
• Phase: N/A
• First received: July 21, 2016
• Last updated: August 9, 2017
• Start date: January 2013
• Est. completion date: January 2017

Study information

• Verified date: August 2017
• Source: Nantes University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 411
• Est. completion date: January 2017
• Est. primary completion date: January 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Aneurysm
• Intracranial Aneurysm

Intervention

Genetic:
• Non-Interventional

Locations

Country	Name	City	State
France	AP-HP, Henri Mondor hospital	Créteil
France	CHD La Roche sur YON	La Roche sur YON
France	Nantes University Hospital	Nantes
France	University Hospital Poitiers	Poitiers
France	University Hospital Rennes	Rennes
France	Rouen University Hospital	Rouen
France	Bordeaux University Hospital	Talence
France	Tours University Hospital	Tours

Sponsors (1)

Lead Sponsor	Collaborator
Nantes University Hospital

Country where clinical trial is conducted

France, 

References & Publications (5)

Canham PB, Finlay HM. Morphometry of medial gaps of human brain artery branches. Stroke. 2004 May;35(5):1153-7. Epub 2004 Mar 11. — View Citation

Rhoton AL Jr. Aneurysms. Neurosurgery. 2002 Oct;51(4 Suppl):S121-58. Review. — View Citation

Rinkel GJ, Djibuti M, Algra A, van Gijn J. Prevalence and risk of rupture of intracranial aneurysms: a systematic review. Stroke. 1998 Jan;29(1):251-6. — View Citation

Ronkainen A, Hernesniemi J, Ryynänen M. Familial subarachnoid hemorrhage in east Finland, 1977-1990. Neurosurgery. 1993 Nov;33(5):787-96; discussion 796-97. Review. — View Citation

Vlak MH, Algra A, Brandenburg R, Rinkel GJ. Prevalence of unruptured intracranial aneurysms, with emphasis on sex, age, comorbidity, country, and time period: a systematic review and meta-analysis. Lancet Neurol. 2011 Jul;10(7):626-36. doi: 10.1016/S1474-4422(11)70109-0. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	DNA analysis to identify new genes (and new physiological pathways) associated to the risk of intracranial aneurysm		Until one year