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

Sponsor
King's College Hospital NHS Trust (Other)
Overall Status
Recruiting
CT.gov ID
NCT06053671
Collaborator
King's College London (Other), Danish Epilepsy Centre (Other)
60
Enrollment
1
Location
1
Arm
36
Anticipated Duration (Months)
1.7
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Genetic: Blood and nasal swab sampling
 N/A

Detailed Description

Primary Objectives:

  1. To identify if somatic mosaicism for mTOR is present in resected tissue from patients with FCDIIA/B, and can be detected in DNA from patient's serum as circulating free DNA (cfDNA) or from nasal epithelial cells collected non-invasively by olfactory mucosal brush swab.

  2. To establish if single cell expression profiling from resected fresh frozen tissue reveals novel FCD causing pathways and single cell RNA sequencing increases the yield of mTOR pathway variant detection.

  3. To determine if phosphorylated upstream and downstream mTOR pathway components can be characterised by immunohistochemistry and Western blot as novel biomarkers of mTOR activation in human FCDII tissue.

Secondary Objectives:

To engage with patients, representatives and charitable organisations to assess feasibility and develop plan to set up a future trial of mTOR inhibitor treatment.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
60 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Diagnostic
Official Title:
Dissecting mTOR Pathway Mosaicism in FCDII-Harbouring Epileptic Brain and Peripheral Tissue.
Actual Study Start Date :
Apr 9, 2023
Anticipated Primary Completion Date :
Apr 8, 2025
Anticipated Study Completion Date :
Apr 8, 2026

Arms and Interventions

Arm Intervention/Treatment
Experimental: Patients with histologically confirmed FCDIIA/B undergoing or post Epilepsy Surgery

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

Genetic: Blood and nasal swab sampling
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.
Other Names:
  • Analysis of Epilepsy Surgical tissue

    		•

    Outcome Measures

    Primary Outcome Measures

    1. somatic mosaicism [2 years]

      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. single cell expression profiling [2 years]

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

    3. phosphorylated targets [2 years]

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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    Epilepsy in Focal Cortical Dysplasia Type IIA/B

    Key Inclusion Criteria:

    1. Adult and Paediatric Patients (male and female)

    2. A histologically proven diagnosis of FCDIIA/B or a suspected diagnosis of FCDIIA/B (on MRI/EEG and PET grounds) awaiting resective Epilepsy surgery.

    3. Able to attend appointment/hospital and undergo sampling of serum and nasal swab

    4. Informed Consent Available

    Key Exclusion Criteria:

    1. Any acute or chronic conditions that could limit the ability of the patient to participate in the study.

    2. Refusal to give informed consent.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 King's College Hospital London United Kingdom

    Sponsors and Collaborators

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

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    King's College Hospital NHS Trust
    ClinicalTrials.gov Identifier:
    NCT06053671
    Other Study ID Numbers:
    • 303113_28022022
    • 22/WA/0326
    First Posted:
    Sep 26, 2023
    Last Update Posted:
    Sep 26, 2023
    Last Verified:
    Sep 1, 2023
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Epilepsy
    Malformations of Cortical Development
    Focal Cortical Dysplasia

    Study Results

    No Results Posted as of Sep 26, 2023