Creation of a Register of Patients With Neonatal-onset Epileptic Encephalopathy (IMPROVE)

November 17, 2025 updated by: Assistance Publique Hopitaux De Marseille

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Estimated)

200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • France
      • Angers, France
        • Not yet recruiting
        • CHU Angers
        • Contact:
          • Patrick Van Bogaert
      • Bordeaux, France
        • Not yet recruiting
        • CHU Bordeaux
        • Contact:
          • Jean-Michel Pedespan
      • Brest, France
        • Not yet recruiting
        • CHU Brest
        • Contact:
          • Jérémie Lefranc
      • Lille, France
        • Not yet recruiting
        • CHRU Lille
        • Contact:
          • Sylvie Nguyen
      • Limoges, France
        • Not yet recruiting
        • CHU Limoges
        • Contact:
          • Cécile Laroche
      • Lyon, France
        • Not yet recruiting
        • Hospices civils Lyon
        • Contact:
          • Gaetan Lesca
        • Sub-Investigator:
          • Dorthée Ville
      • Marseille, France, 13005
        • Recruiting
        • Hôpital La Timone
        • Contact:
      • Montpellier, France
        • Not yet recruiting
        • CHU Montpellier
        • Contact:
          • Agathe ROUBERTIE
      • Paris, France
      • Paris, France
        • Recruiting
        • APHP Pitié Salpetrière
        • Contact:
          • Cyril Mignot
      • Paris, France
        • Not yet recruiting
        • APHP Robert Debré
        • Contact:
          • Stéphane Auvin
      • Rennes, France
        • Not yet recruiting
        • Chu Rennes
        • Contact:
          • Sylvia Napuri
      • Strasbourg, France
        • Not yet recruiting
        • CHRU Strasbourg
        • Contact:
          • Anne De Saint Martin
      • Toulouse, France
        • Not yet recruiting
        • CHU Toulouse
        • Contact:
          • Claude Cances
      • Tours, France
        • Not yet recruiting
        • CHU Tours
        • Contact:
          • Marie-Anne Barthez

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Retrospective observational study initially then prospective with inclusion of all patients with a KCNQ2-REE whose diagnosis was made in the EPIGENE network

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
importance of the developmental disorder
Time Frame: Month 36
Developmental quotient
Month 36
definition of the active phase of epilepsy
Time Frame: Month 36
Presence of at least monthly seizures and interictal EEG showing paroxysmal abnormalities
Month 36

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique Hopitaux De Marseille

Investigators

  • Study Director: Jean Olivier Arnaud, Assistance Publique - Hopitaux de Marseille

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 6, 2021

Primary Completion (Estimated)

September 1, 2029

Study Completion (Estimated)

September 1, 2032

Study Registration Dates

First Submitted

March 14, 2021

First Submitted That Met QC Criteria

March 14, 2021

First Posted (Actual)

March 17, 2021

Study Record Updates

Last Update Posted (Actual)

November 20, 2025

Last Update Submitted That Met QC Criteria

November 17, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2019-51
  • ID-RCB (Other Identifier: 2026-A00289-42)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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