Study of Pathophysiology of Status Epilepticus and Dysimmune Encephalitis (COLETTE)

COLETTE : Study of the Pathophysiology of Status Epilepticus and Dysimmune Encephalitis and Identification of Valuable Biomarkers

COLETTE is an interventional study for which blood, cerebrospinal fluid and post-mortem tissues are collected in patients with status epilepticus or epilepsy associated to dysimmune encephalitis as well as in control patients, to better understand the pathophysiology of these severe epileptic disorders.

Study Overview

• Status: Recruiting
• Conditions: Status Epilepticus; Dysimmune Encephalopathy
• Intervention / Treatment: Other: Blood sampling, cerebrospinal fluid , post-mortem cerebral tissues (NA for the Group 3)

Detailed Description

Epilepsy is one of the most common neurological condition which concerns around 50 million people worldwide. Epilepsy is characterized by a lasting predisposition to generate seizures. Epilepsy can present as heterogenous set of clinical symptoms and is related to extremely varied etiologies. Some epilepsies are triggered by antineuronal autoantibodies and/or complicated by a status epilepticus. These conditions may induce brain atrophy, and severe neurological sequels.

The severity of these epilepsies requires significant efforts to (i) identify new therapeutic strategies able to control the evolution of dysimmune encephalitis and refractory status epilepticus, (ii) to identify their etiologies and (iii) to propose neuroprotective strategies.

Therefore, the investigators will organize a collection of biological samples (blood, cerebrospinal fluid, post-mortem brain tissues) and paraclinical data (electroencephalogram, evoked potential, CT, MRI) in patients with severe epilepsies, whether or not associated with autoantibodies, and/or evolving into status epilepticus.

This study should bring new insights allowing to better understand mechanisms that trigger the emergence of an epileptic brain (epileptogenesis) through :

(i) the identification and characterization of new pathophysiological pathways involving autoimmunity directed against the cerebral cortex and associated with severe epilepsy (ii) the identification and characterization of pathophysiological pathways participating in the excitotoxicity observed in status epilepticus.

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Vincent NAVARRO, Pr; Phone Number: 01 42 16 19 40; Email: vincent.navarro@aphp.fr

Study Locations

• France
  • Paris, France, 75013
    • Recruiting
    • Hopital de la Pitie Salpetriere
    • Contact: Vincent NAVARRO, Pr; Phone Number: 01 42 16 19 40; Email: vincent.navarro@aphp.fr
    • Contact: Virginie LAMBRECQ, Dr; Phone Number: 01 57 27 46 63; Email: virginie.lambrecq@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Group 1:

• Patients aged 2 years or above, with status epilepticus.
• Affiliation to a French social security system excluding "Aide Médicale" Etat (AME).
• Patients or relatives have been informed and given free informed and written consent to participate
• Patients under legal protection (guardianship, curatorship) or not

Group 2:

• Patients aged 2 years or above, with clinical signs of epilepsy associated to dysimmune encephalitis.
• Affiliation to a French social security system excluding "Aide Médicale" Etat (AME).
• Patients or relatives have been informed and given free informed and written consent to participate
• Patients under legal protection (guardianship, curatorship) or not

Group 3:

• Patients aged 18 years or above, without status epilepticus and/or dysimmune encephalitis.
• Affiliation to a French social security system excluding "Aide Médicale" Etat (AME).
• Patients or relatives have been informed and given free informed and written consent to participate
• Patients under legal protection (guardianship, curatorship) or not

Exclusion Criteria:

Group 1:

• Women with known or clinically detected pregnancy.
• Patient deprived of liberty
• Patients with known neurodegenerative disease.

Group 2:

• Women with known or clinically detected pregnancy.
• Patient deprived of liberty
• Patients have been already treated by corticoids or IgIV.

Group 3:

• Women with known or clinically detected pregnancy.
• Patient deprived of liberty.
• Patients with status epilepticus.
• Patients with known neurodegenerative disease, brain tumor, severe head trauma, meningitis, subarachnoid hemorrhages, stroke.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Group 1 : Status epilepticus	Other: Blood sampling, cerebrospinal fluid , post-mortem cerebral tissues (NA for the Group 3); Collection of biological samples and clinical/paraclinical data
Other: Group 2 : Dysimmune encephalitis	Other: Blood sampling, cerebrospinal fluid , post-mortem cerebral tissues (NA for the Group 3); Collection of biological samples and clinical/paraclinical data
Other: Group 3 : Control patients	Other: Blood sampling, cerebrospinal fluid , post-mortem cerebral tissues (NA for the Group 3); Collection of biological samples and clinical/paraclinical data

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of (i) antibodies in the plasma and in the cerebrospinal fluid of patients with dysimmune encephalitis and (ii) biomarkers for neuronal death in the plasma and in the cerebrospinal fluid of patients with status epilepticus	Looking for antibodies with cell-based binding assay or monospecific recombinant assay. Identification of biomarkers for neuronal death with electrochemiluminometric sandwich immunoassays (Kryptor and ModularE170, Roche Diagnostic)	9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of new dysimmune abnormalities	Lymphocyte phenotyping, cytokines quantification	9 months
Identification of specific EEG patterns associated to dysimmune encephalitis and/or status epilepticus	EEG signals will be reviewed and classifiyed according to a EEG-based seizure build-up score in status epilepticus (EaSiBUSSEs)	9 months
Identification of new genetic pathways associated to dysimmune encephalitis and status	Genetic biomarkers	9 months
Identification of new metabolic pathway that may participate in the excitotoxicity observed in status epilepticus or dysimmune encephalitis	Looking for diagnostic and prognosis biomarkers. Characterization of the brain cholesterol homeostasis with UPLC-MS/MS method and enzymatic assays. Evaluation of new biomarkers (proteins, lipids, genes).	9 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Vincent NAVARRO, Pr, Hôpital Pitié Salpêtrière - Assitance Publique Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): November 25, 2020
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: June 4, 2020
• First Submitted That Met QC Criteria: June 4, 2020
• First Posted (Actual): June 9, 2020

Study Record Updates

• Last Update Posted (Actual): November 22, 2023
• Last Update Submitted That Met QC Criteria: November 20, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Epilepsy; Autoimmunity; Status Epilepticus
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Seizures; Neuroinflammatory Diseases; Encephalitis; Brain Diseases; Status Epilepticus
• Other Study ID Numbers: APHP200306; 2020-A00053-36 (Other Identifier: ANSM)

Plan for Individual participant data (IPD)

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