Epilepsy in ChildrenNNAISNCT03916848
Novel Network Analysis of Intracranial Stereoelectroencephalography
A study testing Combined Micro-Macro SEEG Electrodes in people with Epilepsy in Children and Focal Epilepsy, run by Great Ormond Street Hospital for Children NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
Epilepsy is a disorder of the brain which is associated with disabling seizures and affects 100,000 people under 25. Many children with epilepsy also have a learning disability or problems with development. Read more about this study
- Who is it for?
- Ages 3 to 18 years
- Conditions the study is for
- Epilepsy in Children, Focal Epilepsy, Epilepsy Intractable
- What is being tested?
- Combined Micro-Macro SEEG Electrodes
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 16 Jun 2019to Apr 2022
- 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 3 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Undergoing SEEG recording as part of the investigation of their epilepsy at Great Ormond Street Hospital for Children
- Aged 3-18
- Participant/parents provide informed consent for inclusion
Who cannot join
- Lack of informed consent
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Great Ormond Street Hospital NHS Foundation Trust
London, WC1N 3JH
About this study
Epilepsy is a disorder of the brain which is associated with disabling seizures and affects 100,000 people under 25. Many children with epilepsy also have a learning disability or problems with development. Although better outcomes occur in children who are successfully treated early for their epilepsy, 25% continue to have seizures despite best medical treatment.
One potential treatment is a neurosurgical operation to remove parts of the brain that generate seizures. A proportion of these children have electrodes inserted into their brains as part of their clinical assessment, termed stereoelectroencephalography (SEEG), to help localise these regions. Subsequent surgery is not always successful - up to 40% of children will have ongoing seizures 5 years after surgery.
Read more
The purpose of this study is to assess the utility of specially designed SEEG electrodes which can measure signals from single brain cells. These electrodes record the same clinical information as normal SEEG electrodes and are implanted in the same way, but can give the research team extra information at the same time. The investigators aim to assess whether studying the changes in the firing of individual cells, both during and between seizures, improves our ability to localise seizures and therefore improve outcomes following surgery.
As part of this research project, the investigators will not be doing anything that is not already part of the normal investigation and treatment for these children. Children will be recruited to the study during routine outpatient clinic visits. Surgical planning and execution will not be affected. The electrodes are CE licensed for clinical use and do not alter the risks of the operation. Following the period of monitoring, the care of these children would not be altered in any way.
The investigators aim to recruit 30 patients over 3 years. In addition to dissemination via scientific publications and presentations, the findings will be shared with participants and the public.
Read the detailed description
Hypothesis
The hypothesis is that analysis of ictal (during seizure) and interictal (between seizures) single neuronal firing dynamics will identify ictogenic tissue in children undergoing SEEG recording for focal epilepsy.
Study Design
Prospective cohort study.
Sample Size
The investigators will aim to recruit 30 patients over a period of 3 years, of which 50% will have a normal MRI and 50% will have an identifiable lesion. It is not possible to conduct specific sample size calculations for this study but the centre carries out approximately 24 SEEG recordings per year so this target is feasible and achievable.
Participant Journey
The current patient pathway for children with medically refractory epilepsy undergoing pre-surgical evaluation will not be altered by the current study. The suitability for SEEG recording will be determined by the specialist epilepsy multidisciplinary team (MDT) and patients and parents will be invited to the neurosurgical outpatient clinic to discuss the procedure. There is nothing additional that will be required as part of this research study.
If they agree to proceeding with the SEEG recording procedure, patients will be invited to participate in this study during routine outpatient clinic visits. The treating consultant neurosurgeon (who is part of the routine clinical care team) will inform the patients and parents about the study and give them the opportunity to meet with the clinical research fellow. Patients and their parents will have the study explained to them by the research fellow and be given age-specific information sheets. Following an adequate time to digest this information (a few weeks) and an opportunity to ask any questions, the child (if appropriate) and their parents will choose whether or not they wish to participate in the research. If they choose to participate they will be asked to give written informed consent.
The novel combined micro-macro electrodes will then be used during the surgical implantation procedure. The use of these novel electrodes will not change the surgical procedure, which is conducted using robotic assistance to ensure optimal accuracy. The macro electrode recordings will be used for routine clinical analysis and the duration of recording and subsequent analysis of the recordings will not be affected by the micro electrode data captured for research purposes. The clinical SEEG also involves electrical stimulation of the brain which will not be affected by the study. Participation in this study will not preclude participation in these other studies and it may be possible to use the micro electrode data to supplement analyses in these other studies. Subsequent decision making on suitability for a surgical procedure will follow the normal clinical pathway and will not be affected by the micro electrode recording data.
Further participant follow-up will be observational and data will be obtained from routinely available clinical information, including whether or not a surgical resection is carried out and, if so, whether the patient remains seizure-free at follow-up.
The pseudo-anonymised research data will be securely stored via a secure university (UCL) research data storage service in a safe haven. Data will be stored for the duration of the study and 15 years following completion of the study to comply with GOSH guidelines. Data will be analysed according to the pre-specified data analysis plan, outlined elsewhere in this application.
Timeline
- February 2019 - April 2019 (3 months): Study and infrastructure set-up including acquisition of appropriate recording amplifiers and finalisation of data storage arrangements.
- May 2019 - July 2021 (2 years 3 months): Recruitment. Aim to recruit 15 patients per year. Sufficient provision to allow for slow recruitment in the timeline to ensure that adequate sample is achieved for subsequent analysis.
- August 2021 - October 2021 (3 months): Data analysis.
- November 2021 - January 2022 (3 months): Write-up and dissemination of results. The scientific results will be disseminated in the form of peer-reviewed publications \& conference presentations. In addition, sessions will be held to disseminate the results to patients and the public, in the form of information evenings to groups such as Young Epilepsy and Epilepsy Action.
- Conditions
- Epilepsy in Children, Focal Epilepsy, Epilepsy Intractable, Epilepsy, Focal, Intractable Epilepsy, Refractory Epilepsy
- Being tested
- Combined Micro-Macro SEEG Electrodes
- Keywords
- Stereoelectroencephalography, Single unit recording, Single neuron recording, SEEG, Epilepsy surgery
- Medical subject headings
- Epilepsies, Partial, Drug Resistant Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Combined Micro-Macro SEEG ElectrodesProcedure or surgery
The novel combined micro-macro electrodes will then be used during the surgical implantation procedure. The use of these novel electrodes will not change the surgical procedure, which is conducted using robotic assistance to ensure optimal accuracy. The macro electrode recordings will be used for routine clinical analysis and the duration of recording and subsequent analysis of the recordings will not be affected by the micro electrode data captured for research purposes. The clinical SEEG also involves electrical stimulation of the brain which will not be affected by the study.
| Study group | Role | What they receive |
|---|---|---|
| Combined Micro-Macro SEEG Electrodes | Experimental | Implanting SEEG electrodes with combined micro-macro electrodes capable of recording clinical data and experimental micro electrode single unit data Receives: Procedure: Combined Micro-Macro SEEG Electrodes |
What is being measured
The primary outcome is the main question the study is designed to answer.
Analyse single unit behaviour in different brain regions.
We will assess the abnormalities in single neuron firing behaviour both during and between seizures in children undergoing stereoelectroencephalogaphy (SEEG) as part of work-up for epilepsy surgery.
The statistical analysis will include measures of timing coding and population coding of these single units and the investigators will assess these properties in time periods both during and between seizures to assess whether neurons in the seizure onset zone behave differently to those outside the seizure onset zone:
- Timing coding is evaluated using a generalized linear modeling (GLM) approach. An output of the GLM is called a post-spike filter (PSF), which models the propensity for the same neuron to fire again over the course of the subsequent 0.7 seconds.
- Population coding is also evaluated using a GLM by calculating coupling filters (the amount of up and down regulation of all other recorded neurons given that an individual neuron has just fired).
Measured: Recording will continue for a period of 5-10 days, as determined by the clinical team. We will therefore use the data collected over the entire recording period for analysis.
Correlate firing activity of single units to the clinically defined seizure onset zone (SOZ)
Currently, the seizure onset zone (SOZ) is determined by visual analysis of the SEEG recordings at the end of the monitoring period.
We aim to compare the differences in single unit behaviour (as defined above) between and during seizures in neurons inside and outside this clinically defined SOZ to assess if there is a unique behaviour to these neurons.
Measured: Recording will continue for a period of 5-10 days, as determined by the clinical team. We will therefore use the data collected over the entire recording period for analysis.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Apr 2019
- Study start16 Jun 2019
- Primary completionApr 2022 (estimated)
- Study completionApr 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Epilepsy in ChildrenStudies 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Great Ormond Street Hospital for Children NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Rod Scott, PhD, Principal investigator, Great Ormond Street Hospital for Children NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03916848
- Sponsor's protocol ID
- 18NM09
- Acronym
- NNAIS
- Status last verified
- Nov 2021
- First submitted
- 4 Apr 2019
- Last updated
- 19 Nov 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Currently no provision for IPD sharing, will need further ethical approvals to do this.
Study at a glance
From the registry record, last updated by the sponsor on 19 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Novel Network Analysis of Intracranial Stereoelectroencephalography
- ClinicalTrials.gov ID
- NCT03916848
- Acronym / sponsor ID
- NNAIS / 18NM09
- Conditions
- Epilepsy in Children, Focal Epilepsy, Epilepsy Intractable, Epilepsy, Focal, Intractable Epilepsy, Refractory Epilepsy
- Keywords
- Stereoelectroencephalography, Single unit recording, Single neuron recording, SEEG, Epilepsy surgery
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Great Ormond Street Hospital for Children NHS Foundation TrustUniversity, hospital or other
- Study start
- 16 Jun 2019 (actual)
- Primary completion
- Apr 2022 (estimated)
- Study completion
- Apr 2022 (estimated)
- First posted
- 16 Apr 2019 (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.
Epilepsy is a disorder of the brain which is associated with disabling seizures and affects 100,000 people under 25. Many children with epilepsy also have a learning disability or problems with development. Although better outcomes occur in children who are successfully treated early for their epilepsy, 25% continue to have seizures despite best medical treatment.
One potential treatment is a neurosurgical operation to remove parts of the brain that generate seizures. A proportion of these children have electrodes inserted into their brains as part of their clinical assessment, termed stereoelectroencephalography (SEEG), to help localise these regions. Subsequent surgery is not always successful - up to 40% of children will have ongoing seizures 5 years after surgery.
The purpose of this study is to assess the utility of specially designed SEEG electrodes which can measure signals from single brain cells. These electrodes record the same clinical information as normal SEEG electrodes and are implanted in the same way, but can give the research team extra information at the same time. The investigators aim to assess whether studying the changes in the firing of individual cells, both during and between seizures, improves our ability to localise seizures and therefore improve outcomes following surgery.
As part of this research project, the investigators will not be doing anything that is not already part of the normal investigation and treatment for these children. Children will be recruited to the study during routine outpatient clinic visits. Surgical planning and execution will not be affected. The electrodes are CE licensed for clinical use and do not alter the risks of the operation. Following the period of monitoring, the care of these children would not be altered in any way.
The investigators aim to recruit 30 patients over 3 years. In addition to dissemination via scientific publications and presentations, the findings will be shared with participants and the public.
Detailed description
Hypothesis
The hypothesis is that analysis of ictal (during seizure) and interictal (between seizures) single neuronal firing dynamics will identify ictogenic tissue in children undergoing SEEG recording for focal epilepsy.
Study Design
Prospective cohort study.
Sample Size
The investigators will aim to recruit 30 patients over a period of 3 years, of which 50% will have a normal MRI and 50% will have an identifiable lesion. It is not possible to conduct specific sample size calculations for this study but the centre carries out approximately 24 SEEG recordings per year so this target is feasible and achievable.
Participant Journey
The current patient pathway for children with medically refractory epilepsy undergoing pre-surgical evaluation will not be altered by the current study. The suitability for SEEG recording will be determined by the specialist epilepsy multidisciplinary team (MDT) and patients and parents will be invited to the neurosurgical outpatient clinic to discuss the procedure. There is nothing additional that will be required as part of this research study.
If they agree to proceeding with the SEEG recording procedure, patients will be invited to participate in this study during routine outpatient clinic visits. The treating consultant neurosurgeon (who is part of the routine clinical care team) will inform the patients and parents about the study and give them the opportunity to meet with the clinical research fellow. Patients and their parents will have the study explained to them by the research fellow and be given age-specific information sheets. Following an adequate time to digest this information (a few weeks) and an opportunity to ask any questions, the child (if appropriate) and their parents will choose whether or not they wish to participate in the research. If they choose to participate they will be asked to give written informed consent.
The novel combined micro-macro electrodes will then be used during the surgical implantation procedure. The use of these novel electrodes will not change the surgical procedure, which is conducted using robotic assistance to ensure optimal accuracy. The macro electrode recordings will be used for routine clinical analysis and the duration of recording and subsequent analysis of the recordings will not be affected by the micro electrode data captured for research purposes. The clinical SEEG also involves electrical stimulation of the brain which will not be affected by the study. Participation in this study will not preclude participation in these other studies and it may be possible to use the micro electrode data to supplement analyses in these other studies. Subsequent decision making on suitability for a surgical procedure will follow the normal clinical pathway and will not be affected by the micro electrode recording data.
Further participant follow-up will be observational and data will be obtained from routinely available clinical information, including whether or not a surgical resection is carried out and, if so, whether the patient remains seizure-free at follow-up.
The pseudo-anonymised research data will be securely stored via a secure university (UCL) research data storage service in a safe haven. Data will be stored for the duration of the study and 15 years following completion of the study to comply with GOSH guidelines. Data will be analysed according to the pre-specified data analysis plan, outlined elsewhere in this application.
Timeline
- February 2019 - April 2019 (3 months): Study and infrastructure set-up including acquisition of appropriate recording amplifiers and finalisation of data storage arrangements.
- May 2019 - July 2021 (2 years 3 months): Recruitment. Aim to recruit 15 patients per year. Sufficient provision to allow for slow recruitment in the timeline to ensure that adequate sample is achieved for subsequent analysis.
- August 2021 - October 2021 (3 months): Data analysis.
- November 2021 - January 2022 (3 months): Write-up and dissemination of results. The scientific results will be disseminated in the form of peer-reviewed publications \& conference presentations. In addition, sessions will be held to disseminate the results to patients and the public, in the form of information evenings to groups such as Young Epilepsy and Epilepsy Action.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Combined Micro-Macro SEEG Electrodes | Experimental | Procedure: Combined Micro-Macro SEEG ElectrodesImplanting SEEG electrodes with combined micro-macro electrodes capable of recording clinical data and experimental micro electrode single unit data |
Who may qualify
- Ages
- 3 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- Undergoing SEEG recording as part of the investigation of their epilepsy at Great Ormond Street Hospital for Children
- Aged 3-18
- Participant/parents provide informed consent for inclusion
Key exclusion criteria (1 listed)
- Lack of 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 |
|---|---|---|
| Combined Micro-Macro SEEG ElectrodesThe novel combined micro-macro electrodes will then be used during the surgical implantation procedure. The use of these novel electrodes will not change the surgical procedure, which is conducted using robotic assistance to ensure optimal accuracy. The macro electrode recordings will be used for routine clinical analysis and the duration of recording and subsequent analysis of the recordings will not be affected by the micro electrode data captured for research purposes. The clinical SEEG also involves electrical stimulation of the brain which will not be affected by the study. | Procedure or surgery | Combined Micro-Macro SEEG Electrodes |
Primary outcome
Analyse single unit behaviour in different brain regions.
Time frame: Recording will continue for a period of 5-10 days, as determined by the clinical team. We will therefore use the data collected over the entire recording period for analysis.
We will assess the abnormalities in single neuron firing behaviour both during and between seizures in children undergoing stereoelectroencephalogaphy (SEEG) as part of work-up for epilepsy surgery. The statistical analysis will include measures of timing coding and population coding of these single units and the investigators will assess these properties in time periods both during and between seizures to assess whether neurons in the seizure onset zone behave differently to those outside the seizure onset zone: 1. Timing coding is evaluated using a generalized linear modeling (GLM) approach. An output of the GLM is called a post-spike filter (PSF), which models the propensity for the same neuron to fire again over the course of the subsequent 0.7 seconds. 2. Population coding is also evaluated using a GLM by calculating coupling filters (the amount of up and down regulation of all other recorded neurons given that an individual neuron has just fired).
Correlate firing activity of single units to the clinically defined seizure onset zone (SOZ)
Time frame: Recording will continue for a period of 5-10 days, as determined by the clinical team. We will therefore use the data collected over the entire recording period for analysis.
Currently, the seizure onset zone (SOZ) is determined by visual analysis of the SEEG recordings at the end of the monitoring period. We aim to compare the differences in single unit behaviour (as defined above) between and during seizures in neurons inside and outside this clinically defined SOZ to assess if there is a unique behaviour to these neurons.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Nov 2021.
- Individual participant dataSharing planned: Undecided. Currently no provision for IPD sharing, will need further ethical approvals to do this.
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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.
Rod Scott, PhD principal investigator
Great Ormond Street Hospital for Children NHS Foundation Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Combined Micro-Macro SEEG Electrodes in people with Epilepsy in Children and Focal Epilepsy, run by Great Ormond Street Hospital for Children NHS Foundation 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 3 inclusion and 1 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 Nov 2021. 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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Analyse single unit behaviour in different brain regions. (time frame: Recording will continue for a period of 5-10 days, as determined by the clinical team. We will therefore use the data collected over the entire recording period for analysis.). The study lists 2 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 19 Nov 2021; AzTrials last refreshed its copy on 7 Nov 2026.