Liquid Biopsies for Detecting Somatic Mutations in Sporadic Cerebral Arteriovenous Malformations. Contribution of Sampling From the Drainage Vein of the Malformation.
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 16
- 试验地点
- 3
- 主要终点
- Evaluate genetic mutations identified by liquid biopsies on the drainage vein of AVMs.
研究概览
简要总结
Cerebral arteriovenous malformations (CAVMs) are abnormal vessels located on the surface of the brain or within the cerebral parenchyma, causing abnormal communication between the arterial and venous networks, without the interposition of the capillary bed. The main risk associated with these malformations is rupture, which causes intracranial bleeding and can lead to serious sequelae or even death. CAVMs (except those of clearly identified genetic origin [< 5%], such as mutations associated with Rendu-Osler disease) have long been considered to be of non-genetic origin.
However, somatic genetic mutations that activate the RAS/RAF/MEK/ERK (MAPK) signalling pathway have recently been identified in surgical specimens of cAVMs. Furthermore, targeted inhibition of this pathway is effective in treating these malformations in animals and appears to be effective in extracranial arteriovenous malformations, particularly superficial ones.
详细描述
Next-generation sequencing of circulating DNA in liquid biopsies is a promising new and minimally invasive approach for studying the presence of mutations in arteriovenous malformations.
The goal of treating a cAVM is to obliterate the malformation in order to prevent or avoid the risk of haemorrhage. Several therapeutic modalities may be used, which can be combined: microsurgery, endovascular embolisation, and/or radiosurgery. However, these are invasive treatments that are not without risk.
The detection of mutations by liquid biopsies would enable the development of targeted, non-invasive drug therapies against these cAVMs.
The population consists of patients aged 18 years or older with cAVMs, for whom treatment by venous embolisation was recommended during a multidisciplinary consultation meeting.
This research focuses on identifying somatic genetic mutations that activate the RAS/RAF/MEK/ERK (MAPK) signalling pathway in cAVMs. These mutations have already been identified in surgical specimens. This research aims to evaluate the genetic mutations identified by liquid biopsies on the drainage vein of cAVMs and the prevalence of each mutation.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years
- •Treated for cAVM
- •Indication for embolisation treatment decided upon during a multidisciplinary team meeting (MDT)
- •Venous embolisation, with or without arterial embolisation
- •Patients informed about the study and willing to participate
排除标准
- •Extra-cerebral arteriovenous malformations
- •Under legal protection measures (guardianship/curatorship, etc.)
- •Pregnancy
- •Not eligible for intravenous treatment
结局指标
主要结局
Evaluate genetic mutations identified by liquid biopsies on the drainage vein of AVMs.
时间窗: Embolisation procedure (D0), i.e. a maximum of 45 days after the patient has agreed to participate
determination of each mutation identified in the drainage vein of AVMs,
Assessment of the prevalence of each mutation identified by liquid biopsies on the drainage vein of AVMs
时间窗: Embolisation procedure (D0), i.e. a maximum of 45 days after the patient has agreed to participate
Evaluation of the prevalence of each mutation identified in the drainage vein of AVMs, with calculation of the exact 95% confidence interval.
次要结局
- Evaluation of the imaging characteristics of cAVMs for each of the mutations identified.(Embolisation procedure (D0), i.e. a maximum of 45 days after the patient has agreed to participate)
- Evaluate genetic mutations identified by liquid biopsies on the peripheral vein of AVMs.(Embolisation procedure (D0), i.e. a maximum of 45 days after the patient has agreed to participate)
- Assessment of the prevalence of each mutation identified by liquid biopsies on the peripheral vein of AVMs(Embolisation procedure (D0), i.e. a maximum of 45 days after the patient has agreed to participate)