Epilepsy IntractableNCT06602570
The Mosaic Brain: a New Diagnostic Approach in Focal Epilepsies
An observational study of Epilepsy Intractable and Epilepsy in Children, run by Institute of Child Health.
Trial summary
Overall, this observational cohort study aims to: 1. Improve our understanding of the genetic architecture of childhood focal epilepsies. 2. Develop a liquid biopsy of cerebrospinal fluid (CSF) and assess feasibility to detect cerebral mosaicism using cell-free DNA (cfDNA) analysis and evaluate its performance against… Read more about this study
- Who is it for?
- Ages 6 months to 18 years
- Conditions the study is for
- Epilepsy Intractable, Epilepsy in Children
- How many people
- 40 participants
- Where
- No sites listed yet
- Study dates
- 1 Oct 2024to 1 Sep 2026
- Phase
- Observational
- 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 6 months to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: - Children in the epilepsy surgery service at GOSH.
Who may be able to join
- Children in the epilepsy surgery pathway at Great Ormond Street Hospital (GOSH) with a clear or suspected MRI lesion.
- All children undergoing SEEG at GOSH. Children for which consent was obtained from themselves or, if appropriate, from their legal representatives.
- Children in whom there are no clinical contraindication to having a lumbar puncture procedure pre-surgery.
- Both sexes.
- Under the age of 18.
Who cannot join
- Children that although undergoing epilepsy treatment or testing for an ischaemic lesion.
- Children with malignant brain tumours.
- Children in whom there are contraindications to performing a lumbar puncture procedure.
Trial locations and contacts
No sites are listed yet.
About this study
Overall, this observational cohort study aims to:
- Improve our understanding of the genetic architecture of childhood focal epilepsies.
- Develop a liquid biopsy of cerebrospinal fluid (CSF) and assess feasibility to detect cerebral mosaicism using cell-free DNA (cfDNA) analysis and evaluate its performance against brain tissue on the panel testing.
- Develop a methodology to use trace tissue from Stereoelectroencephalography (SEEG) DNA and assess feasibility to detect cerebral mosaicism and evaluate its performance against brain tissue on the panel testing.
- Validate the use of the liquid biopsy and SEEG trace tissue for use in the English National Health Service clinical services and share with other Genomic Laboratory Hubs.
Read the detailed description
Epilepsy is characterised by recurrent epileptic seizures, and is the most common brain disease affecting children, significantly reducing their quality of life. Understanding the cause of epilepsy is key, as it can help doctors to identify the most effective treatment. This is an urgent issue as 30% of all children with epilepsy do not respond to currently available treatments.
In some children, seizures can start in an area of abnormal brain structure which can be removed with epilepsy surgery.
We see 150 children a year with epilepsy suspected to be caused by a brain lesion. As part of their evaluation, we do genetic testing in blood, as we know that changes in their DNA (mutations) can cause epilepsy in 30-40% of children.
It is now known that mutations are found in some areas of brain responsible for seizures but these are not present in the blood. This is mosaicism, when genetic variation affects only a subgroup of cells or tissues in an individual. Understanding these genetic changes in the brain tissue will help us understand how epilepsy starts and may help us design new treatments. Recently, we designed a new genetic test to pick up these mosaic mutations in brain tissue. However, current methods to detect mosaicism require the use of brain tissue, which limits testing to those children who qualify for surgery.
To expand testing to more children, without the need for surgery, we want to focus our work in using alternative samples, such as cell-free DNA cerebrospinal fluid (CSF) and trace-tissue DNA from trace cells collected from Stereoelectroencephalography (SEEG) electrodes.
We aim to further our understanding of brain mosaicism in epilepsy, using the current available tests, as well as aim to increase access to testing by developing methods to use samples collected using less invasive and pre-surgical methods.
- Conditions
- Epilepsy Intractable, Epilepsy in Children
- Medical subject headings
- Drug Resistant Epilepsy
What is being measured
The primary outcome is the main question the study is designed to answer.
Measure concordance of genetic results for brain mosaicism testing between brain tissue and alternative samples.
Measured: 24 months
Secondary outcomes (4)
Present and compare DNA quality metrics from the several samples types using different methodologies and select the methods yielding better sample quality.
Measured: 24 months
Measure concordance between variant allele frequency (VAF) from brain tissue mosaic genetic testing and VAF calculated using alternative samples.
Measured: 24 months
Present and compare mosaic genetic variability results between alternative samples (cell-free DNA and trace tissue DNA) and peripheral blood DNA.
Measured: 24 months
Present descriptive statistics detailing changes to patient management and genetic counselling directly resulting from a genetic mosaic diagnosis.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2024
- Study start1 Oct 2024 (estimated)
- Primary completion1 Sep 2026 (estimated)
- Study completion1 Sep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Epilepsy IntractableStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Institute of Child Health
- Sponsor type
- University, hospital or other
- Collaborators
- Great Ormond Street Hospital for Children NHS Foundation Trust
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06602570
- Sponsor's protocol ID
- 23BM09
- Status last verified
- Jul 2024
- First submitted
- 17 Sep 2024
- Last updated
- 19 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Mosaic Brain: a New Diagnostic Approach in Focal Epilepsies
- ClinicalTrials.gov ID
- NCT06602570
- Acronym / sponsor ID
- 23BM09
- Conditions
- Epilepsy Intractable, Epilepsy in Children
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Institute of Child HealthUniversity, hospital or other
- Collaborators
- Great Ormond Street Hospital for Children NHS Foundation Trust
- Study start
- 1 Oct 2024 (estimated)
- Primary completion
- 1 Sep 2026 (estimated)
- Study completion
- 1 Sep 2026 (estimated)
- First posted
- 19 Sep 2024 (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.
Overall, this observational cohort study aims to:
- Improve our understanding of the genetic architecture of childhood focal epilepsies.
- Develop a liquid biopsy of cerebrospinal fluid (CSF) and assess feasibility to detect cerebral mosaicism using cell-free DNA (cfDNA) analysis and evaluate its performance against brain tissue on the panel testing.
- Develop a methodology to use trace tissue from Stereoelectroencephalography (SEEG) DNA and assess feasibility to detect cerebral mosaicism and evaluate its performance against brain tissue on the panel testing.
- Validate the use of the liquid biopsy and SEEG trace tissue for use in the English National Health Service clinical services and share with other Genomic Laboratory Hubs.
Detailed description
Epilepsy is characterised by recurrent epileptic seizures, and is the most common brain disease affecting children, significantly reducing their quality of life. Understanding the cause of epilepsy is key, as it can help doctors to identify the most effective treatment. This is an urgent issue as 30% of all children with epilepsy do not respond to currently available treatments.
In some children, seizures can start in an area of abnormal brain structure which can be removed with epilepsy surgery.
We see 150 children a year with epilepsy suspected to be caused by a brain lesion. As part of their evaluation, we do genetic testing in blood, as we know that changes in their DNA (mutations) can cause epilepsy in 30-40% of children.
It is now known that mutations are found in some areas of brain responsible for seizures but these are not present in the blood. This is mosaicism, when genetic variation affects only a subgroup of cells or tissues in an individual. Understanding these genetic changes in the brain tissue will help us understand how epilepsy starts and may help us design new treatments. Recently, we designed a new genetic test to pick up these mosaic mutations in brain tissue. However, current methods to detect mosaicism require the use of brain tissue, which limits testing to those children who qualify for surgery.
To expand testing to more children, without the need for surgery, we want to focus our work in using alternative samples, such as cell-free DNA cerebrospinal fluid (CSF) and trace-tissue DNA from trace cells collected from Stereoelectroencephalography (SEEG) electrodes.
We aim to further our understanding of brain mosaicism in epilepsy, using the current available tests, as well as aim to increase access to testing by developing methods to use samples collected using less invasive and pre-surgical methods.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 6 months to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- - Children in the epilepsy surgery service at GOSH.
Key inclusion criteria (5 listed)
- Children in the epilepsy surgery pathway at Great Ormond Street Hospital (GOSH) with a clear or suspected MRI lesion.
- All children undergoing SEEG at GOSH. Children for which consent was obtained from themselves or, if appropriate, from their legal representatives.
- Children in whom there are no clinical contraindication to having a lumbar puncture procedure pre-surgery.
- Both sexes.
- Under the age of 18.
Key exclusion criteria (3 listed)
- Children that although undergoing epilepsy treatment or testing for an ischaemic lesion.
- Children with malignant brain tumours.
- Children in whom there are contraindications to performing a lumbar puncture procedure.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Measure concordance of genetic results for brain mosaicism testing between brain tissue and alternative samples.
Time frame: 24 months
4 secondary outcomes
Present and compare DNA quality metrics from the several samples types using different methodologies and select the methods yielding better sample quality.
Time frame: 24 months
Measure concordance between variant allele frequency (VAF) from brain tissue mosaic genetic testing and VAF calculated using alternative samples.
Time frame: 24 months
Present and compare mosaic genetic variability results between alternative samples (cell-free DNA and trace tissue DNA) and peripheral blood DNA.
Time frame: 24 months
Present descriptive statistics detailing changes to patient management and genetic counselling directly resulting from a genetic mosaic diagnosis.
Time frame: 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
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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.
Questions about this trial
What is this clinical trial studying?
An observational study of Epilepsy Intractable and Epilepsy in Children, run by Institute of Child Health.
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 5 inclusion and 3 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 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
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 Flavia Matos Santo, MSc (020 7405 9200 ext. 4944, flavia.matossanto@gosh.nhs.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Measure concordance of genetic results for brain mosaicism testing between brain tissue and alternative samples. (time frame: 24 months). 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 19 Sep 2024.