Creation of a Register of Patients With Neonatal-onset Epileptic Encephalopathy

Epileptic Encephalopathy Clinical Trial

— IMPROVE  

Official title:

Creation of a Register of Patients With Neonatal-onset Epileptic Encephalopathy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04802135
• Other study ID #: 2019-51
• Secondary ID: ID-RCB
• Status: Recruiting
• Start date: March 6, 2021
• Est. completion date: September 2025

Study information

• Verified date: January 2024
• Source: Assistance Publique Hopitaux De Marseille
• Contact: Mathieu Milh
• Phone: 0491322903
• Email: mathieu.milh[@]ap-hm.fr
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Electrical activity emerges in the third trimester of pregnancy, plays an important role in the construction of cortical maps, and is impaired in patients with severe early epileptic encephalopathies (EOEE). EOEE are rare and severe epileptic syndromes characterized by epilepsy that begins within the first three months of life and is associated with rapid deterioration of motor, cognitive and behavioral skills.

There is a genetic basis for the EOEE. Together with other laboratories, the investigators have identified de novo pathogenic variants in the KCNQ2 gene encoding the Kv7.2 subunit of the Kv7 / M potassium channel, a channel known to control neuronal excitability in the brain and spinal cord. via the current M (IM). Pathogenic variants of the KCNQ2 gene represent the main cause of EOEE and the term KCNQ2-related epileptic encephalopathy (KCNQ2-REE) is now used to define this condition.

KCNQ2-REE patients have a remarkably homogeneous phenotype at the start, with epilepsy that begins in the first days after birth, seizures that result in tonic muscle spasms that last from 1 to 10 seconds, and an interictal EEG called "suppression-burst". "That is, paroxysmal bursts of activity interspersed with periods of electrical silence. In this group, more than 50% of the patients present a remission of the epilepsy and a quasi-normalization of the EEG which can occur a few weeks to several months after the onset of the seizures. Despite this positive evolution in terms of seizures, the developmental progression is abnormal and the phenotype is severe with an absence of language, autistic behavior and a subsequent development of motor disorders such as diplegia, spasticity, ataxia or dystonia.

The ambition of this project is to increase knowledge of epileptic encephalopathies linked to KCNQ2 at the clinical and molecular levels, to decipher the pathophysiological mechanisms and to propose therapeutic strategies.

This project aims to better describe the clinical, EEG, imaging, developmental and long-term follow-up characteristics of patients carrying the KCNQ2 mutation identified in the laboratory.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: September 2025
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Epilepsy beginning before 1 month of life, and requiring the initiation of anti-epileptic treatment

• Without occasional cause

• Without brain malformation explaining epilepsy

• No opposition from parents / guardians

• Possibility for parents to complete parent questionnaires

Exclusion Criteria:

• Neonatal attacks of occasional cause (glycemic disorder, infection, etc.)

• Acquired neonatal epilepsy (post-anoxic encephalopathy, stroke sequelae, etc.)

• Neonatal epilepsy related to a brain malformation

Related Conditions & MeSH terms

• Brain Diseases
• Epilepsy
• Epileptic Encephalopathy

Intervention

Other:
• Survey
directive questionnaire administered during an individual face-to-face interview

Locations

Country	Name	City	State
France	CHU Angers	Angers
France	CHU Bordeaux	Bordeaux
France	CHU Brest	Brest
France	CHRU Lille	Lille
France	CHU Limoges	Limoges
France	Hospices Civils Lyon	Lyon
France	Hôpital La Timone	Marseille
France	CHU Montpellier	Montpellier
France	APHP Pitié Salpêtrière	Paris
France	APHP Robert Debré	Paris
France	Hôpital Necker	Paris
France	CHU Rennes	Rennes
France	CHRU Strasbourg	Strasbourg
France	CHU Toulouse	Toulouse
France	CHU Tours	Tours

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique Hopitaux De Marseille

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	importance of the developmental disorder	Developmental quotient	Month 36
Primary	definition of the active phase of epilepsy	Presence of at least monthly seizures and interictal EEG showing paroxysmal abnormalities	Month 36