Genetic and Electrophysiologic Study in Focal Drug-resistant Epilepsies

NCT ID: NCT02890641

Last Updated: 2026-01-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

450 participants

Study Classification

OBSERVATIONAL

Study Start Date

2015-12-17

Study Completion Date

2031-12-31

Brief Summary

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Brain somatic mutations in genes belonging to the mTOR signaling pathway are a frequent cause of cortical malformations, including focal cortical dysplasia and hemimegalencephaly, while SLC35A2 mutations are identified in MOGHE.

This study aims to identify brain somatic mutations in paired blood-brain samples and perform functional validation in children with drug-resistant focal epilepsy

Detailed Description

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Conditions

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Refractory Focal Epilepsy Focal Cortical Dysplasia Hemimegalencephaly Tuberous Sclerosis Mild Malformation of Cortical Development With Oligodendroglial Hyperplasia in Epilepsy (MOGHE)

Study Design

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Observational Model Type

FAMILY_BASED

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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Children undergoing epilepsy surgery at the Rothschild Foundation, Paris.

Sequencing of paired blood-brain DNA samples

Sampling of blood, frozen resected tissues, and cerebrospinal fluid (CSF)

Intervention Type GENETIC

Sampling of blood, frozen resected tissue, and cerebrospinal fluid (CSF); sequencing of paired blood-brain DNA samples

Interventions

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Sampling of blood, frozen resected tissues, and cerebrospinal fluid (CSF)

Sampling of blood, frozen resected tissue, and cerebrospinal fluid (CSF); sequencing of paired blood-brain DNA samples

Intervention Type GENETIC

Eligibility Criteria

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Inclusion Criteria

* Children with focal drug-resistant epilepsy including Focal Cortical Dysplasia, Hemimegalencephaly, Tuberous Sclerosis, Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE), Hypothalamic Hamartomas, Sturge-Weber syndrome, Rasmussen encephalitis, gliomas)
* Their parents who have signed informed consent 1) for their child's participation (for parents) and 2) for themselves
* Social security coverage or foreign regime recognized in France

Exclusion Criteria

* refusal to participate in the study
* contraindication to anaesthesia, to MRI or to surgery
* no medical insurance coverage
Minimum Eligible Age

3 Months

Maximum Eligible Age

25 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Fondation Ophtalmologique Adolphe de Rothschild

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Mathilde CHIPAUX, MD

Role: PRINCIPAL_INVESTIGATOR

Fondation A de Rothschild

Stephanie Baulac, PhD

Role: STUDY_CHAIR

Institut du Cerveau et de la Moelle Epinière

Locations

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Fondation Ophtalmologique Adolphe de Rothschld

Paris, , France

Site Status RECRUITING

Countries

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France

Central Contacts

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Amelie YAVCHITZ, MD

Role: CONTACT

+33 1 48 03 64 54

Mathilde Chipaux, MD

Role: CONTACT

01 48 03 69 43

Facility Contacts

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Amélie Yavchitz, MD

Role: primary

+33 1 48 03 64 54

References

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Baldassari S, Ribierre T, Marsan E, Adle-Biassette H, Ferrand-Sorbets S, Bulteau C, Dorison N, Fohlen M, Polivka M, Weckhuysen S, Dorfmuller G, Chipaux M, Baulac S. Dissecting the genetic basis of focal cortical dysplasia: a large cohort study. Acta Neuropathol. 2019 Dec;138(6):885-900. doi: 10.1007/s00401-019-02061-5. Epub 2019 Aug 23.

Reference Type RESULT
PMID: 31444548 (View on PubMed)

Bonduelle T, Hartlieb T, Baldassari S, Sim NS, Kim SH, Kang HC, Kobow K, Coras R, Chipaux M, Dorfmuller G, Adle-Biassette H, Aronica E, Lee JH, Blumcke I, Baulac S. Frequent SLC35A2 brain mosaicism in mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE). Acta Neuropathol Commun. 2021 Jan 6;9(1):3. doi: 10.1186/s40478-020-01085-3.

Reference Type RESULT
PMID: 33407896 (View on PubMed)

Lee WS, Baldassari S, Chipaux M, Adle-Biassette H, Stephenson SEM, Maixner W, Harvey AS, Lockhart PJ, Baulac S, Leventer RJ. Gradient of brain mosaic RHEB variants causes a continuum of cortical dysplasia. Ann Clin Transl Neurol. 2021 Feb;8(2):485-490. doi: 10.1002/acn3.51286. Epub 2021 Jan 12.

Reference Type RESULT
PMID: 33434304 (View on PubMed)

Kim S, Baldassari S, Sim NS, Chipaux M, Dorfmuller G, Kim DS, Chang WS, Taly V, Lee JH, Baulac S. Detection of Brain Somatic Mutations in Cerebrospinal Fluid from Refractory Epilepsy Patients. Ann Neurol. 2021 Jun;89(6):1248-1252. doi: 10.1002/ana.26080. Epub 2021 Apr 20.

Reference Type RESULT
PMID: 33834539 (View on PubMed)

Barba C, Blumcke I, Winawer MR, Hartlieb T, Kang HC, Grisotto L, Chipaux M, Bien CG, Hermanovska B, Porter BE, Lidov HGW, Cetica V, Woermann FG, Lopez-Rivera JA, Canoll PD, Mader I, D'Incerti L, Baldassari S, Yang E, Gaballa A, Vogel H, Straka B, Macconi L, Polster T, Grant GA, Krskova L, Shin HJ, Ko A, Crino PB, Krsek P, Lee JH, Lal D, Baulac S, Poduri A, Guerrini R; SLC35A2 Study Group. Clinical Features, Neuropathology, and Surgical Outcome in Patients With Refractory Epilepsy and Brain Somatic Variants in the SLC35A2 Gene. Neurology. 2023 Jan 31;100(5):e528-e542. doi: 10.1212/WNL.0000000000201471. Epub 2022 Oct 28.

Reference Type RESULT
PMID: 36307217 (View on PubMed)

Checri R, Chipaux M, Ferrand-Sorbets S, Raffo E, Bulteau C, Rosenberg SD, Doladilhe M, Dorfmuller G, Adle-Biassette H, Baldassari S, Baulac S. Detection of brain somatic mutations in focal cortical dysplasia during epilepsy presurgical workup. Brain Commun. 2023 Jun 1;5(3):fcad174. doi: 10.1093/braincomms/fcad174. eCollection 2023.

Reference Type RESULT
PMID: 37324239 (View on PubMed)

Ribierre T, Bacq A, Donneger F, Doladilhe M, Maletic M, Roussel D, Le Roux I, Chassoux F, Devaux B, Adle-Biassette H, Ferrand-Sorbets S, Dorfmuller G, Chipaux M, Baldassari S, Poncer JC, Baulac S. Targeting pathological cells with senolytic drugs reduces seizures in neurodevelopmental mTOR-related epilepsy. Nat Neurosci. 2024 Jun;27(6):1125-1136. doi: 10.1038/s41593-024-01634-2. Epub 2024 May 6.

Reference Type RESULT
PMID: 38710875 (View on PubMed)

Sanders MWCB, Koeleman BPC, Brilstra EH, Jansen FE, Baldassari S, Chipaux M, Sim NS, Ko A, Kang HC, Blumcke I, Lal D, Baulac S, Lee JH, Aronica E, Braun KPJ. Somatic variant analysis of resected brain tissue in epilepsy surgery patients. Epilepsia. 2024 Dec;65(12):e209-e215. doi: 10.1111/epi.18148. Epub 2024 Oct 26.

Reference Type RESULT
PMID: 39460693 (View on PubMed)

Baldassari S, Klingler E, Teijeiro LG, Doladilhe M, Raoux C, Roig-Puiggros S, Bizzotto S, Couturier J, Gilbert A, Sami L, Ribierre T, Aronica E, Adle-Biassette H, Chipaux M, Jabaudon D, Baulac S. Single-cell genotyping and transcriptomic profiling of mosaic focal cortical dysplasia. Nat Neurosci. 2025 May;28(5):964-972. doi: 10.1038/s41593-025-01936-z. Epub 2025 Apr 30.

Reference Type RESULT
PMID: 40307383 (View on PubMed)

Related Links

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Other Identifiers

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GDR_2015_15

Identifier Type: -

Identifier Source: org_study_id

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