Liquid Biopsies for the Detection of Somatic Mutations in bAVMs

NCT06494358 | Recruiting

• 1 other identifier: APHP240718
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

"Personalized medicine has revolutionized patient care, particularly in oncology. Brain arteriovenous malformations (bAVMs) are abnormal vessels located on the surface of the brain or within the brain parenchyma, causing abnormal communication between arterial and venous networks, without the interposition of the capillary bed. The main risk of these malformations is rupture, leading to intracranial bleeding, which can cause severe sequelae or even death. bAVMs (except those of clearly identified genetic origin \[\< 5%\], such as mutations associated with Rendu-Osler disease) have long been considered non-genetic in origin. However, somatic genetic mutations activating the RAS/RAF/MEK/ERK (MAPK) signaling pathway have recently been identified in surgical specimens of bAVMs. Additionally, 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. Next-generation sequencing of circulating DNA on liquid biopsies is a promising and minimally invasive approach to studying the presence of mutations in arteriovenous malformations. The treatment of a bAVM aims to obliterate the malformation to prevent or avoid the risk of hemorrhage. It may involve several therapeutic modalities: microsurgery, endovascular embolization, and radiosurgery. These treatments can be combined, and microsurgery is often preceded by pre-surgical embolization, aimed at reducing the hemorrhagic risk of the intervention. However, these are invasive treatments, not without risk. The identification of mutations through liquid biopsies could enable the development of non-invasive targeted therapies against these bAVMs. This research aims to identify somatic genetic mutations activating the MAPK signaling pathway in bAVMs. These mutations have already been identified in surgical specimens. This research aims to evaluate the diagnostic performances of liquid biopsies (detection of genetic mutations in blood samples, i.e., circulating DNA), with the gold standard being the detection of the same mutations in surgical specimens."

Conditions

Brain Arterial Disease

Keywords

brain arteriovenous malformation; liquid biopsies

Outcome Measures

Primary Outcomes (1)

• Study of the diagnostic performance of 1) liquid biopsies on the artery in the immediate vicinity of the nidus, 2) liquid biopsies on the peripheral vein, for the detection of somatic genetic mutations in cAVMs

  \- Sensitivity / Specificity / Positive Predictive Value / Negative Predictive Value Compared with the gold standard: detection of mutations on surgical specimens

  18 months

Secondary Outcomes (5)

• - Prevalence of mutations on surgical specimens

  18 months

• - Prevalence of mutations on the artery in the immediate vicinity of the nidus

  18 months

• - Prevalence of peripheral vein mutations

  18 months

• - General patient characteristics for each of the mutations identified

  18 months

• - Imaging characteristics of cAVMs for each of the mutations identified

  18 months

Interventions

liquid biopsies and surgery specimen analysis OTHER

liquid biopsies and surgery specimen analysis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The population consists of patients aged 18 years or older with a bAVM, for whom treatment by microsurgery with preoperative embolization at Pitié-Salpêtrière Hospital was decided upon in a multidisciplinary consultation meeting.

You may not qualify if:

• Extra-cerebral arteriovenous malformations
• Under legal protection (guardianship/curators, etc.)
• Pregnancy
• Not eligible for combined treatment (embolization followed by surgery)

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Unité de neuroradiologie interventionnelle, hôpital Pitié-Salpêtrière

Paris, 75571, France

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Circulating DNA: There will be 1 tube of 2 mL (arterial sample near the nidus, collected as part of standard care but conserved for research) and 2 tubes of 10 mL (peripheral blood sampled from the care catheter), in addition to the samples taken as part of standard care during the embolization procedure.

MeSH Terms

Conditions

Intracranial Arterial Diseases

Interventions

Liquid Biopsy

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Biopsy; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Investigative Techniques

Central Study Contacts

Frederic Clarençon, MD,PhD

CONTACT

0033 1 42 16 35 99; frederic.clarencon@aphp.fr

Study Design

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

Study Record Dates

• First Submitted: July 2, 2024
• First Posted: July 10, 2024
• Study Start: April 1, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: May 16, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Beginning 3 months and ending 3 years following article publication. Requests out of these time frame can also be submitted to the sponsor
• Access Criteria: Researchers who provide a methodologically sound proposal.

Locations

FR (1)