Mos-FED (Mosaicism in Focal Epilepsy Cortical Dysplasia Tissue)

NCT06053671 | Recruiting DMC

• 2 other identifiers: 303113_2802202222/WA/0326
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Focal cortical dysplasia (FCD) is a malformation of brain development, the most common cause of drug-resistant epilepsy and often caused by mutations in mammalian target of rapamycin (mTOR) pathway genes. Patients with FCD develop drug-resistant seizures. This study will look at FCD tissue removed during epilepsy surgery and aims to detect mutations in mTOR pathway genes in brain cells. Secondly, the investigators will establish if evidence of mutations found in brain cells can also be detected as circulating free DNA (cfDNA) in blood. By looking at which genes are made into proteins in individual cells found in epilepsy surgical tissue (single cell expression profiling),the investigators will attempt to identify new genetic targets in FCD. The main outcome will be finding new causes of epilepsy with FCD and the development of new diagnostic and screening tools.

Conditions

Focal Cortical Dysplasia; Epilepsy

Outcome Measures

Primary Outcomes (3)

• somatic mosaicism

  This study will measure and report the rate of somatic mosaicism for mTOR pathway genes in resected brain tissue and peripheral blood and nasal mucosal cells from patients with FCDIIA/B assessed by panel genetic sequencing of genomic and free circulating DNA .

  2 years

• single cell expression profiling

  This study will measure and report novel FCD causing mutations through single cell expression profiling from resected fresh frozen tissue.

  2 years

• phosphorylated targets

  This study will measure phosphorylation of upstream and downstream mTOR pathway components by immunohistochemistry and Western blot in human FCDII tissue.

  2 years

Study Arms (1)

Patients with histologically confirmed FCDIIA/B undergoing or post Epilepsy Surgery

EXPERIMENTAL

Genetic screening of DNA samples (blood, mucosal swab, brain tissue)

Genetic: Blood and nasal swab sampling

Interventions

Blood and nasal swab sampling GENETIC

Genetic screening of DNA samples (blood, mucosal swab, brain tissue) from 60-100 patients with histologically confirmed diagnosis of FCDIIA/B identified from Epilepsy Surgery Databases.

Also known as: Analysis of Epilepsy Surgical tissue

Patients with histologically confirmed FCDIIA/B undergoing or post Epilepsy Surgery

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult and Paediatric Patients (male and female)
• A histologically proven diagnosis of FCDIIA/B or a suspected diagnosis of FCDIIA/B (on MRI/EEG and PET grounds) awaiting resective Epilepsy surgery.
• Able to attend appointment/hospital and undergo sampling of serum and nasal swab
• Informed Consent Available

You may not qualify if:

• Any acute or chronic conditions that could limit the ability of the patient to participate in the study.
• Refusal to give informed consent.

Sponsors & Collaborators

• King's College Hospital NHS Trust: lead
• King's College London: collaborator
• Danish Epilepsy Centre: collaborator

Study Sites (1)

King's College Hospital

London, United Kingdom

RECRUITING

MeSH Terms

Conditions

Focal Cortical Dysplasia; Epilepsy

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations; Nervous System Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Brain Diseases; Central Nervous System Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Central Study Contacts

Laura Mantoan Ritter, MD PhD

CONTACT

00442032999000; laura.mantoan@kcl.ac.uk

Sylvini Lalnunhlimi

CONTACT

+44 (0) 20 7848 5162; sylvine.1.lalnunhlimi@kcl.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 5, 2023
• First Posted: September 26, 2023
• Study Start: April 9, 2023
• Primary Completion: April 8, 2025
• Study Completion: April 8, 2026
• Last Updated: October 23, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: Data will be accessible to others outside of our team once published or within three years of the end of the grant, to allow for completion of publications and project proposals.
• Access Criteria: Governance Digital data available to the wider community will be controlled by KORDS application procedures. Before any data are published, we will conduct a Data Protection Impact Assessment (DPIA) in accordance with the UK GDPR. Requests for unpublished and/or genomic data will be controlled by a Data Management Committee. Data and Biological Material Transfer and Sharing Agreements which defines the scope of use, timeline and further distribution limits will be agreed. Data will be accessible to others outside of our team once published or within three years of the end of the grant, to allow for completion of publications and project proposals. We will attempt to limit restriction to human data sharing by gaining participant's consent for data sharing, and by anonymising data. Our consent form will clearly describe proposed data sharing schemes, their benefits and potential risks, whilst safeguarding participants.

Locations

GB (1)