I-CAN Biocollection

NCT02712892 | Completed

• 1 other identifier: RC15_0304
• Study Type: observational
• Target: 3,078
• Locations: 1 country
• Sites: 20

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.

Conditions

Intracranial Aneurysm

Outcome Measures

Primary Outcomes (1)

• Presence or absence of genetic abnormalitie

  Identification of genetic abnormalities segregant with the presence of intracranial aneurysms in the informative families recruited. Sequencing of the whole exome in a cohort of patients carriers of familial forms of intracranial aneurysms. Analysis of blood level of the GAIA 1 protein in a large cohort of familial and sporadic carriers of intracranial aneurysms

  Until one year

Interventions

Non Interventional Study GENETIC

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The initial stage of this biocollection based on the recruitment of large families for genetic linkage analysis. This is a first step to 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 is 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.

You may qualify if:

• 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.
• biocollection of Written Consent for participation in the collection of biological samples
• Any patient consulting for IA and some typical bifurcation
• Patients aged 20 years or older
• biocollection of Written Consent for participation in the collection of biological samples
• Patients who have shown the inability or refusal to sign the consent informed biocollection
• syndromic diagnosis known as AIC 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

Sponsors & Collaborators

• Nantes University Hospital: lead
• Institut National de la Santé Et de la Recherche Médicale, France: collaborator

Study Sites (20)

Angers University Hospital

Angers, 49933, France

Location

Besançon University Hospital

Besançon, 25030, France

Location

Bordeaux University Hospital

Bordeaux, 33404, France

Location

Henri Mondor Hospital (AP-HP)

Créteil, 94000, France

Location

Dijon University Hospital

Dijon, 21079, France

Location

Grenoble University Hospital

Grenoble, 38043, France

Location

La Reunion University Hospital

La Réunion, 97448, France

Location

Kremlin-Bicêtre University Hospital (AP-HP)

Le Kremlin-Bicêtre, 94270, France

Location

Limoges University Hospital

Limoges, 87042, France

Location

Nancy University Hospital

Nancy, 54035, France

Location

Nantes University Hospital

Nantes, 44093, France

Location

Lariboisière University Hospital (AP-HP)

Paris, 75010, France

Location

La Pitié-Salpétrière University Hospital (AP-HP)

Paris, 75013, France

Location

Sainte Anne Hospital

Paris, 75014, France

Location

Rotschild Fundation

Paris, 75019, France

Location

Poitiers University Hospital

Poitiers, 86021, France

Location

Rennes University Hospital

Rennes, 35033, France

Location

Rouen University Hospital

Rouen, 76031, France

Location

Toulouse University Hospital

Toulouse, 31059, France

Location

Tours University Hospital

Tours, 37044, France

Location

Related Publications (1)

• L'Allinec V, Chatel S, Karakachoff M, Bourcereau E, Lamoureux Z, Gaignard A, Autrusseau F, Jouan S, Vion AC, Loirand G, Desal H, Naggara O, Redon R, Edjlali M, Bourcier R. Prediction of Unruptured Intracranial Aneurysm Evolution: The UCAN Project. Neurosurgery. 2020 Jul 1;87(1):150-156. doi: 10.1093/neuros/nyaa093.

  PMID: 32374868 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

For one patient included: * 2 Ethylenediaminetetraacetic acid (EDTA) tubes for DNA (5mL) * 2 dry tubes for serum (5mL)

MeSH Terms

Conditions

Intracranial Aneurysm

Condition Hierarchy (Ancestors)

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

Study Officials

• Hubert DESAL, Pr

  Nantes University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: FAMILY BASED
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2016
• First Posted: March 18, 2016
• Study Start: March 3, 2016
• Primary Completion: December 19, 2019
• Study Completion: December 31, 2020
• Last Updated: September 9, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (20)