Focal Cortical DysplasiaMosFEDNCT06053671
Mos-FED (Mosaicism in Focal Epilepsy Cortical Dysplasia Tissue)
A study testing Blood and nasal swab sampling in people with Focal Cortical Dysplasia and Epilepsy, run by King's College Hospital NHS Trust at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Focal Cortical Dysplasia, Epilepsy
- What is being tested?
- Blood and nasal swab sampling
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 9 Apr 2023to 8 Apr 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Any acute or chronic conditions that could limit the ability of the patient to participate in the study.
- Refusal to give informed consent.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
King's College Hospital
London
Laura Mantoan, MD PhD, laura.mantoan@kcl.ac.uk
About this study
Official title: Dissecting mTOR Pathway Mosaicism in FCDII-Harbouring Epileptic Brain and Peripheral Tissue.
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.
Read the detailed description
Primary Objectives:
- 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.
- 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.
- 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.
- Conditions
- Focal Cortical Dysplasia, Epilepsy
- Being tested
- Blood and nasal swab sampling
- Medical subject headings
- Focal Cortical Dysplasia, Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood and nasal swab samplingGenetic
Also called Analysis of Epilepsy Surgical tissue
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.
| Study group | Role | What they receive |
|---|---|---|
| Patients with histologically confirmed FCDIIA/B undergoing or post Epilepsy Surgery | Experimental | Genetic screening of DNA samples (blood, mucosal swab, brain tissue) Receives: Genetic: Blood and nasal swab sampling |
What is being measured
The primary outcome is the main question the study is designed to answer.
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 .
Measured: 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.
Measured: 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.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2023
- Study start9 Apr 2023
- Primary completion8 Apr 2025 (estimated)
- Study completion8 Apr 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Focal Cortical DysplasiaStudies of the same condition, open and under way.
- More trials run by King's College Hospital NHS TrustThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- King's College Hospital NHS Trust
- Sponsor type
- University, hospital or other
- Collaborators
- King's College London, Danish Epilepsy Centre
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06053671
- Sponsor's protocol ID
- 303113_28022022
- Other IDs
- 22/WA/0326
- Acronym
- MosFED
- Status last verified
- Oct 2024
- First submitted
- 5 Sep 2023
- Last updated
- 23 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Anonymised clinical data associated with the tissue will be deposited with the King's Open Research Data System (KORDS), a trusted research environment, which meets UKRI data retention and sharing requirements. KORDS also enables published datasets to be long-term discoverable, accessible and citable
Study at a glance
From the registry record, last updated by the sponsor on 23 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dissecting mTOR Pathway Mosaicism in FCDII-Harbouring Epileptic Brain and Peripheral Tissue.
- ClinicalTrials.gov ID
- NCT06053671
- Acronym / sponsor ID
- MosFED / 303113_28022022
- Conditions
- Focal Cortical Dysplasia, Epilepsy
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- King's College Hospital NHS TrustUniversity, hospital or other
- Collaborators
- King's College London, Danish Epilepsy Centre
- Study start
- 9 Apr 2023 (actual)
- Primary completion
- 8 Apr 2025 (estimated)
- Study completion
- 8 Apr 2026 (estimated)
- First posted
- 26 Sep 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Primary Objectives:
- 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.
- 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.
- 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
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients with histologically confirmed FCDIIA/B undergoing or post Epilepsy Surgery | Experimental | Genetic: Blood and nasal swab samplingGenetic screening of DNA samples (blood, mucosal swab, brain tissue) |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (2 listed)
- Any acute or chronic conditions that could limit the ability of the patient to participate in the study.
- Refusal to give informed consent.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Blood and nasal swab samplingAlso: Analysis of Epilepsy Surgical tissueGenetic 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. | Genetic | Patients with histologically confirmed FCDIIA/B undergoing or post Epilepsy Surgery |
Primary outcome
somatic mosaicism
Time frame: 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 .
single cell expression profiling
Time frame: 2 years
This study will measure and report novel FCD causing mutations through single cell expression profiling from resected fresh frozen tissue.
phosphorylated targets
Time frame: 2 years
This study will measure phosphorylation of upstream and downstream mTOR pathway components by immunohistochemistry and Western blot in human FCDII tissue.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Oct 2024.
- Individual participant dataSharing planned: Yes. Anonymised clinical data associated with the tissue will be deposited with the King's Open Research Data System (KORDS), a trusted research environment, which meets UKRI data retention and sharing requirements. KORDS also enables published datasets to be long-term discoverable, accessible and citable
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Blood and nasal swab sampling in people with Focal Cortical Dysplasia and Epilepsy, run by King's College Hospital NHS Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 23 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Laura Mantoan Ritter, MD PhD (00442032999000 ext. 8339, laura.mantoan@kcl.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
somatic mosaicism (time frame: 2 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Oct 2024.