Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT05821790 |
| Other study ID # |
APHP230289 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
May 2023 |
| Est. completion date |
May 2024 |
Study information
| Verified date |
April 2023 |
| Source |
Assistance Publique - Hôpitaux de Paris |
| Contact |
Michel KALAMARIDES, MD |
| Phone |
1 42 16 31 12 |
| Email |
michel.kalamarides[@]aphp.fr |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Meningiomas are the most common primary tumors of the central nervous system in adults.
High-grade forms have a high frequency of neurofibromatosis 2 (NF2) mutations and represent
25% of meningiomas, with multiple recurrences associated with morbidity and reduced survival
without medical options, including immunotherapy. The meninges play a key role in
neuro-immune communication through the diversity of their immune cells and the presence of
meningeal lymphatic vessels (MLV). Recent data, including from our team, shows frequent
infiltration of lymphocytes and myeloid cells specific to benign meningiomas. Our hypothesis
is that the immune microenvironment composed of meningeal immune cells and MLVs regulates the
malignant histological progression of NF2-mutated meningiomas and their immune surveillance
evasion behavior This study aims to characterize the different cellular populations of the
meningioma microenvironment. We will describe the exact participation of immune and vascular
cell populations in the initiation and progression of meningioma, using MRI imaging and
surgical biopsies of the dura mater and meningioma in patients undergoing neurosurgery for
meningioma resection.
Description:
The objective of this study is to characterize the different cellular populations of the
microenvironment of meningioma, particularly the immune and vascular cell populations, in
order to better understand their role in the initiation and progression of this tumor. For
this purpose, we will use MRI imaging and surgical biopsies of the dura mater and meningioma
to characterize cellular phenotypes and their interactions in the tissue microenvironment.
The research will be conducted on a cohort of patients treated for meningioma in neurosurgery
services. Samples required for the study will be obtained from surgical waste of patients who
underwent meningioma resection. Data necessary for the study will be collected from the
patient's medical records, MRI examinations, and data specific to the characteristics of the
surgical waste. Prospective patients will be informed of the study through an information
note. Patients who do not object to their participation will undergo neurosurgery
intervention in accordance with the usual service protocol. During the intervention, surgical
waste will be produced, including the meningioma and adjacent dura mater, which will be
collected under the responsibility of the neuro-pathologist who will also take fragments for
routine diagnostic histological analysis. We will then perform a targeted mutational analysis
associated with neuropathological evaluation of the tumor grade in order to select 10 cases
of grade I meningioma and 10 cases of grade II and III meningioma carrying the NF2 mutation.
An in-depth analysis will then be carried out on these samples using 10x Genomic's
single-cell RNA sequencing (scRNA-seq) technology. This analysis will help to understand the
tumor's heterogeneity and establish the phenotype and differentiation trajectory of tumor
cells, dura mater cells, and associated immune cells. In addition to RNA analysis, the
expression of genetic signatures will be validated by RNAscope tests, while Hyperion imaging
will allow visualization of the interrelationships between different types of cells and their
spatial distribution. The iDISCO+ immunolabeling combined with three-dimensional fluorescence
microscopy imaging will enable visualization of specific protein expression profiles of
meningioma and dura mater cell types in 3D. Once the analyses are complete, meningioma and
dura mater samples will be destroyed. Preoperative MRI images will also be retrieved and
analyzed.
