Study of Pathophysiology of Status Epilepticus and Dysimmune Encephalitis

Status Epilepticus Clinical Trial

— COLETTE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04421846
• Other study ID #: APHP200306
• Secondary ID: 2020-A00053-36
• Status: Recruiting
• Phase: N/A
• Start date: November 25, 2020
• Est. completion date: June 1, 2027

Study information

• Verified date: July 2023
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Vincent NAVARRO, Pr
• Phone: 01 42 16 19 40
• Email: vincent.navarro[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 400
• Est. completion date: June 1, 2027
• Est. primary completion date: June 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Brain Diseases
• Dysimmune Encephalopathy
• Encephalitis
• Status Epilepticus

Intervention

Other:
• Blood sampling, cerebrospinal fluid , post-mortem cerebral tissues (NA for the Group 3)
Collection of biological samples and clinical/paraclinical data

Locations

Country	Name	City	State
France	Hôpital de la Pitié Salpêtrière	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Identification of new dysimmune abnormalities	Lymphocyte phenotyping, cytokines quantification	9 months
Secondary	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
Secondary	Identification of new genetic pathways associated to dysimmune encephalitis and status	Genetic biomarkers	9 months
Secondary	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