Liquid Biopsies for Detecting Somatic Mutations in Sporadic Cerebral Arteriovenous Malformations.
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Search for activating somatic genetic mutations.
- Who it may be relevant to
- Registry conditions: Cerebral Arteriovenous Malformations. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- France
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
Liquid Biopsies for Detecting Somatic Mutations in Sporadic Cerebral Arteriovenous Malformations. Contribution of Sampling From the Drainage Vein of the Malformation.
Overview
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.
Detailed description
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.
These liquid biopsies will be performed during embolisation surgery by sampling the drainage vein of the malformation and peripheral venous blood (no additional procedures compared to usual care).
Interventions
- Other Search for activating somatic genetic mutations
This research aims to evaluate the genetic mutations identified by liquid biopsies on the drainage vein of AVMs, and the prevalence of each mutation. These liquid biopsies will be performed during the embolisation procedure by sampling the drainage vein of the malformation and peripheral venous blood (no additional procedures compared to standard care).
Primary outcome measures
- Evaluate genetic mutations identified by liquid biopsies on the drainage vein of AVMs. [Time frame: 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 drainage vein of AVMs [Time frame: Embolisation procedure (D0), i.e. a maximum of 45 days after the patient has agreed to participate]
Secondary outcome measures (3)
- Evaluation of the imaging characteristics of cAVMs for each of the mutations identified. [Time frame: 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. [Time frame: 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 [Time frame: Embolisation procedure (D0), i.e. a maximum of 45 days after the patient has agreed to participate]
Eligibility criteria
Inclusion criteria
- 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
Exclusion criteria
- Extra-cerebral arteriovenous malformations
- Under legal protection measures (guardianship/curatorship, etc.)
- Pregnancy
- Not eligible for intravenous treatment
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Observational model
- Cohort
Study locations
France · 3 centers
- University Hospital of Caen — Caen
- Hôpital la Pitié-Salpêtrière — Paris
- University Hospital of Rouen — Rouen
Identifiers
NCT: NCT07103304 · 2023/0310/OB · N° IDRCB : 2025-A00757-42