Multimodal Study of the Human Brain Epilepsy Tissue (TIPI²)

The TIPI2 study is a blood and tissue collection protocol to create an annotated biorepository to support research in drug-resistant epilepsy.

The aim of the study will be to identify new pathophysiological pathways. For this purpose, the investigators will investigate with a multimodal approach blood and brain samples from patients undergoing a surgery for focal drug-resistant epilepsy. The adult patients will be enrolled either during the pre-surgical evaluation or right before the surgery.

Study Overview

• Status: Recruiting
• Conditions: Focal Drug-resistant Epilepsy
• Intervention / Treatment: Other: Blood and tissue collection

Detailed Description

This study aims to investigate blood and brain samples from patients with drug-resistant epilepsy in order to identify new pathophysiological biomarkers.

The investigators will first conduct multimodal research, including:

• electrophysiological analyses
• immunohistochemistry and genetic studies
• biochemistry analyses

Samples will be stored at -80°C for future research.

Patients will undergo a follow-up evaluation within the 36 months following the surgery. New clinical data and biological samples will be collected then.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Vincent M. Navarro, MD, PHD; Phone Number: +33 01 42 16 19 40; Email: Vincent.navarro@aphp.fr
• Study Contact Backup: Name: Aurélie Ms Hanin, PharmD, PhD; Phone Number: +33 01 57 27 40 56; Email: Aurelie.hanin@icm-institute.org

Study Locations

• France
  • Paris, France, 75013
    • Recruiting
    • Department of Neurology, Epilepsy Unit, Pitié-Salpêtrière Hospital
    • Contact: Vincent M. Navarro, MD, PHD; Phone Number: +33 01 42 16 19 40; Email: Vincent.navarro@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18 yo or above
• patients with a focal drug-resistant epilepsy
• patients hospitalized for a pre-surgical evaluation or for an epilepsy surgery
• consent obtained from the patient, or legally authorized representative
• affiliated to a social security system

Exclusion Criteria:

• None

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: epileptic patients; All patients will be enrolled in the same arm. Patients can be enrolled during the pre-surgical evaluation (group 1) or in the days preceding the surgery (group 2).

Other: Blood and tissue collection; Blood will be collected for group 1 during (i) the enrolment visit, (ii) in the 24 hours following a seizure, (iii)before the surgery and (iv) in the 36 months following the surgery. The left-over tissue, not useful for diagnostic purpose, will be kept for research. Blood will be collected for group 2 right before the surgery and in the 36 months following the surgery. The left-over tissue not useful for diagnostic purpose will be kept for research.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of new pathophysiological mechanisms leading to focal drug-resistant epilepsy : analysis by immuno-histological methods	The investigator will identify inflammatory cells (astrocytes, microglia, lymphocytes and neutrophil polynuclear cells) in the post-operative brain tissue, and will calculate if there is an increase of a part of these cells in the area, defined as the seizure onset zone, as compared to the non-epileptic areas.	At the day of surgery; analyses are based on the post-operative tissues
Identification of new pathophysiological mechanisms leading to focal drug-resistant epilepsy : analysis by electrophysiological methods	The investigator will record local field potentials and neuronal firing rate from post-operative tissues, and we will research an increase of the rate of interictal epileptiform discharges and of the frequency of the neuronal firing in the seizure-onset zone, as compared to those in non-epileptic areas.	At the day of surgery; analyses are based on the post-operative tissues
Identification of new pathophysiological mechanisms leading to focal drug-resistant epilepsy : analysis by RNA sequencing methods	The investigator will measure the expression of mRNA in cells of different parts of the post-operative brain tissue, and we will research specific expression of mRNA in the Seizure onset zone, as compared to that in other non-epileptic areas.	At the day of surgery; analyses are based on the post-operative tissues

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of new pathophysiological mechanisms associated with the occurrence of a seizure : analysis of biomarkers by ELISA methods	The investigator will measure several proteins by Elisa, and we will define if there is a specific increase of some proteins in the sample after a seizure, as compared to the level of these proteins far from a seizure.	from inclusion day to 36 months after the surgery
Identification of new pathophysiological mechanisms associated with an active epilepsy : analysis of biomarkers by ELISA methods	The investigator will measure the different blood cells by flow cytometry, and we will define if there is a specific increase of some cell populations in the sample from epileptic patients, as compared to the level of these cell populations in non-epileptic patients.	from inclusion day to 36 months after the surgery
Identification of new pathophysiological mechanisms associated with an active epilepsy : analysis of blood cell subtypes by flow cytometry	The investigator will measure the different blood cells by flow cytometry, and we will define if there is a specific increase of some cell populations in the sample from epileptic patients, as compared to the level of these cell populations in non-epileptic patients.	from inclusion day to 36 months after the surgery
Identification of new pathophysiological mechanisms associated with an active epilepsy : analysis of inflammation biomarkers by digital ultra-sensitive quantitation of proteins methods	The investigator will measure several inflammatory proteins including cytokines, and we will define if there is a specific increase of some proteins in the sample from epileptic patients, as compared to the level of these proteins in non-epileptic patients.	from inclusion day to 36 months after the surgery

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Institut National de la Santé Et de la Recherche Médicale, France; ICM Co. Ltd.
• Investigators: Principal Investigator: Vincent M. Navarro, MD, PHD, APHP

Study record dates

Study Major Dates

• Study Start (Actual): February 29, 2024
• Primary Completion (Estimated): February 28, 2030
• Study Completion (Estimated): February 28, 2037

Study Registration Dates

• First Submitted: May 22, 2023
• First Submitted That Met QC Criteria: August 30, 2023
• First Posted (Actual): September 1, 2023

Study Record Updates

• Last Update Posted (Estimated): March 6, 2024
• Last Update Submitted That Met QC Criteria: March 4, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Surgery; Biomarkers; Biorepository; Focal drug-resistant epilepsy
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Drug Resistant Epilepsy
• Other Study ID Numbers: APHP230479

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Data are available upon reasonable request

The procedures carried out with the French data privacy authority (CNIL, Commission nationale de l'informatique et des libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients.

Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations.

• IPD Sharing 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.
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No