跳至主要内容
临床试验/NCT02712892
NCT02712892已完成不适用

IntraCranial ANeurysms: From Familial Forms to Pathophysiological Mechanisms

Nantes University Hospital20 个研究点 分布在 1 个国家目标入组 3,078 人开始时间: 2016年3月3日最近更新:
适应症

试验速览

阶段
不适用
状态
已完成
入组人数
3,078
试验地点
20
主要终点
Presence or absence of genetic abnormalitie

研究概览

简要总结

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.

研究设计

研究类型
Observational
观察模型
Family Based
时间视角
Prospective

入排标准

年龄范围
20 Years 至 —(Adult, Older Adult)
性别
All
接受健康志愿者

入选标准

  • 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
  • Combined with an arteriovenous malformation
  • Blister-like
  • Pathology of the cerebral white matter detected on MRI suggestive:
  • Mutation COL4A1

排除标准

  • 未提供

结局指标

主要结局

Presence or absence of genetic abnormalitie

时间窗: Until one year

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

次要结局

未报告次要终点

研究者

申办方类型
Other
责任方
Sponsor

研究点 (20)

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