EpilepsyMASTNCT04383028
MELD as an Adjunct for SEEG Trajectories
A study testing MELD algorithm use to aid in the planning of SEEG electrode trajectories in people with Epilepsy and Epilepsy, Focal, 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, Epilepsy, Focal, Epilepsy, Refractory
- What is being tested?
- MELD algorithm use to aid in the planning of SEEG electrode trajectories
- 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
- 1 Jul 2020to 30 May 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
- Patients aged 3-18 undergoing SEEG recording as part of the investigation of their epilepsy at Great Ormond Street Hospital for Children.
Who cannot join
- Tuberous sclerosis
- Prior resective epilepsy surgery
- Insufficient imaging datasets for the algorithm
- Lack of informed consent
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
Great Ormond Street Hospital NHS Foundation Trust
London, WC1N 3JH
Aswin Chari, MRCS, +447726780817, aswin.chari@gosh.nhs.uk
Martin Tisdall, PhD, +447726780817, martin.tisdall@gosh.nhs.uk
About this study
Official title: MELD as an Adjunct for SEEG Trajectories (MAST Trial)
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 planning of where to place SEEG electrodes relies on experts (neurologists, neurophysiologists and neurosurgeons) using information from multiple sources, which are used to generate hypotheses about where the seizures are coming from. The main components are the patient's magnetic resonance imaging (MRI) scan and video-electroencephalography (EEG) recordings during seizures. Using this information, between 5-18 electrodes are implanted and the recordings continue for 5-15 days in hospital. A focus is identified in about 75% of cases which means that the focus is sometimes missed.
This prospective single arm pilot study aims to assess a new automated lesion detection algorithm, MELD, designed to identify focal cortical dysplasias (the most common pathology associated with focal epilepsy in children) on otherwise 'normal' MRI scans. The investigators will assess whether MELD can be used to improve the targeting of abnormalities in children undergoing SEEG recording at Great Ormond Street Hospital
Read the detailed description
Epilepsy is a disorder of the brain that is associated with disabling seizures. It affects 100,000 children in the UK, 25-30% of whom will be classed as drug resistant.3 In these children, there is increasing evidence that resective epilepsy surgery in appropriate candidates can lead to seizure freedom and improve quality of life and cognitive outcomes.4-6 However, about 30% of children do not achieve seizure freedom following epilepsy surgery and data suggests that these figures are not improving over time despite increasing use of intracranial evaluation via stereoelectroencephalography (SEEG). 7
The planning of where to place SEEG electrodes currently relies on an expert multidisciplinary team consisting of neurologists, neurophysiologists and neurosurgeons. Information from multiple sources, mainly the patient's magnetic resonance imaging (MRI) scan and video-electroencephalography (EEG) recording, are used to generate hypotheses about the location of the clinical seizure onset zone (SOZ). Using this information, between 5-18 electrodes are implanted and the recordings continue for 5-15 days in hospital. In a retrospective review of 75 SEEG cases, a focus was identified in about 77% of cases which means that the focus is sometimes missed.
This prospective single arm pilot study to aims assess a new automated lesion detection algorithm, MELD, designed to identify focal cortical dysplasias (the most common pathology associated with focal epilepsy in children) on otherwise 'normal' MRI scans.1 This algorithm was developed in-house by collaborators in this grant application. In our subsequent retrospective study of 34 SEEG patients, the algorithm colocalised with the SEEG-defined SOZ in 62% of all patients with a cortical SOZ and 86% of all patients with a histologically confirmed focal cortical dysplasia.2 Importantly, there were 3 patients whose SOZ was thought to be missed on SEEG who had MELD-identified lesions that were not implanted. In order to improve the algorithm, investigators have subsequently launched an international multicentre collaboration (https://meldproject.github.io//) to increase the number of lesion positive and control scans available to train the algorithm, improving its sensitivity, specificity and accuracy. This project has gathered over 550 lesional and 350 control scans, which will be used to train the algorithm. The prospective MAST Trial is therefore the ideal next step in the evaluating the utility of the MELD algorithm in identifying abnormal areas of the brain that could be responsible for seizures.
- Conditions
- Epilepsy, Epilepsy, Focal, Epilepsy, Refractory
- Being tested
- MELD algorithm use to aid in the planning of SEEG electrode trajectories
- Medical subject headings
- Epilepsy, Epilepsies, Partial, Drug Resistant Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MELD algorithm use to aid in the planning of SEEG electrode trajectoriesProcedure or surgery
During the routine SEEG planning meetings, the planning of SEEG trajectories, including the number and location of electrodes, will follow the usual clinical pathway and be planned according to the expertise of the attending neurosurgeon, neurophysiologist and neurologist at the multidisciplinary team meeting. Once the trajectories have been planned, anonymised scans for each patient (linked to them via a unique study ID) will be run through the MELD classifier and the top 3 MELD identified lesion clusters will be considered for further implantation.
These top 3 MELD classifier identified clusters will then be merged with the existing clinical plan to assess if each of the clusters are already being sampled by an SEEG electrode. If there is already an electrode in each lesion, no adjustments will be made. If there are clusters that are not being recorded from, and it is technically possible, extra electrodes (up to 3) will be added to record from these additional locations.
| Study group | Role | What they receive |
|---|---|---|
| MELD-assisted SEEG trajectory planning | Experimental | Following routine clinical planning, the MELD algorithm will be run on the enrolled patient's scans. Up to 3 extra electrodes may be used to target lesion clusters identified by the algorithm such that the investigators will record from the top 3 clusters, with the aim of improving the rate of identification of a focal seizure onset zone in patients undergoing SEEG. Receives: Procedure: MELD algorithm use to aid in the planning of SEEG electrode trajectories |
What is being measured
The primary outcome is the main question the study is designed to answer.
Additional contacts in neurophysiologically defined seizure onset zone
For each patient, the investigators will assess whether any of the additional electrodes (added as part of the trial to record from detected lesions) were in the neurophysiologically (SEEG) defined seizure onset zone. This will be a dichotomous yes/no outcome for each patient.
Measured: Baseline (During inpatient admission)
Secondary outcomes (8)
Pre-implantation confidence
Pre-implantation confidence of the MDT members in identifying a seizure onset zone (prior to MELD information) ie. a measure of the difficulty of the SEEG exploration on Likert scale 0-10
Measured: Baseline (During inpatient admission)
Number of electrodes added
Simple number
Measured: Baseline (During inpatient admission)
Number of electrodes added
Number of electrodes already in identified lesions
Measured: Baseline (During inpatient admission)
Was a MELD-identified lesion part of the SOZ (and if so how many?)
Yes/no and simple numerical outcome
Measured: Baseline (During inpatient admission)
Would the SOZ have been identified without MELD?
Yes/No outcome
Measured: Baseline (During inpatient admission)
Blinded neurophysiological assessment of the SOZ contacts with and without additional electrodes
Description of contacts in SOZ with and without additional electrodes
Measured: Baseline (During inpatient admission)
Putative resection boundaries with and without the additional electrodes, to be modelled by a neurosurgeon ie. a measure of whether or not this would have changed subsequent surgical strategy
Description of resection and how it may have changes
Measured: Baseline (During inpatient admission)
adverse events such as bleeding
Safety of adding additional electrodes
Measured: Baseline (During inpatient admission)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2020
- Study start1 Jul 2020
- Primary completion30 Apr 2022 (estimated)
- Study completion30 May 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for EpilepsyStudies 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
- Diagnosis
- 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
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04383028
- Sponsor's protocol ID
- 19NI10
- Acronym
- MAST
- Status last verified
- Nov 2021
- First submitted
- 21 Apr 2020
- Last updated
- 19 Nov 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: As is current good scientific practice, heavily anonymised matrices of processed data and the processing code will be made available as part of any publication. These datasets will be fully anonymised and in abstract space (ie will not contain primary MRI scan images or electrode locations) and will rather be matrices that will in no way be relatable to the patient. They will definitely not contain any patient identifiable information and will not be able to be back-processed to get identifiable information.
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
- MELD as an Adjunct for SEEG Trajectories (MAST Trial)
- ClinicalTrials.gov ID
- NCT04383028
- Acronym / sponsor ID
- MAST / 19NI10
- Conditions
- Epilepsy, Epilepsy, Focal, Epilepsy, Refractory
- 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
- 1 Jul 2020 (actual)
- Primary completion
- 30 Apr 2022 (estimated)
- Study completion
- 30 May 2022 (estimated)
- First posted
- 11 May 2020 (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 planning of where to place SEEG electrodes relies on experts (neurologists, neurophysiologists and neurosurgeons) using information from multiple sources, which are used to generate hypotheses about where the seizures are coming from. The main components are the patient's magnetic resonance imaging (MRI) scan and video-electroencephalography (EEG) recordings during seizures. Using this information, between 5-18 electrodes are implanted and the recordings continue for 5-15 days in hospital. A focus is identified in about 75% of cases which means that the focus is sometimes missed.
This prospective single arm pilot study aims to assess a new automated lesion detection algorithm, MELD, designed to identify focal cortical dysplasias (the most common pathology associated with focal epilepsy in children) on otherwise 'normal' MRI scans. The investigators will assess whether MELD can be used to improve the targeting of abnormalities in children undergoing SEEG recording at Great Ormond Street Hospital
Detailed description
Epilepsy is a disorder of the brain that is associated with disabling seizures. It affects 100,000 children in the UK, 25-30% of whom will be classed as drug resistant.3 In these children, there is increasing evidence that resective epilepsy surgery in appropriate candidates can lead to seizure freedom and improve quality of life and cognitive outcomes.4-6 However, about 30% of children do not achieve seizure freedom following epilepsy surgery and data suggests that these figures are not improving over time despite increasing use of intracranial evaluation via stereoelectroencephalography (SEEG). 7
The planning of where to place SEEG electrodes currently relies on an expert multidisciplinary team consisting of neurologists, neurophysiologists and neurosurgeons. Information from multiple sources, mainly the patient's magnetic resonance imaging (MRI) scan and video-electroencephalography (EEG) recording, are used to generate hypotheses about the location of the clinical seizure onset zone (SOZ). Using this information, between 5-18 electrodes are implanted and the recordings continue for 5-15 days in hospital. In a retrospective review of 75 SEEG cases, a focus was identified in about 77% of cases which means that the focus is sometimes missed.
This prospective single arm pilot study to aims assess a new automated lesion detection algorithm, MELD, designed to identify focal cortical dysplasias (the most common pathology associated with focal epilepsy in children) on otherwise 'normal' MRI scans.1 This algorithm was developed in-house by collaborators in this grant application. In our subsequent retrospective study of 34 SEEG patients, the algorithm colocalised with the SEEG-defined SOZ in 62% of all patients with a cortical SOZ and 86% of all patients with a histologically confirmed focal cortical dysplasia.2 Importantly, there were 3 patients whose SOZ was thought to be missed on SEEG who had MELD-identified lesions that were not implanted. In order to improve the algorithm, investigators have subsequently launched an international multicentre collaboration (https://meldproject.github.io//) to increase the number of lesion positive and control scans available to train the algorithm, improving its sensitivity, specificity and accuracy. This project has gathered over 550 lesional and 350 control scans, which will be used to train the algorithm. The prospective MAST Trial is therefore the ideal next step in the evaluating the utility of the MELD algorithm in identifying abnormal areas of the brain that could be responsible for seizures.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| MELD-assisted SEEG trajectory planning | Experimental | Procedure: MELD algorithm use to aid in the planning of SEEG electrode trajectoriesFollowing routine clinical planning, the MELD algorithm will be run on the enrolled patient's scans. Up to 3 extra electrodes may be used to target lesion clusters identified by the algorithm such that the investigators will record from the top 3 clusters, with the aim of improving the rate of identification of a focal seizure onset zone in patients undergoing SEEG. |
Who may qualify
- Ages
- 3 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (1 listed)
- Patients aged 3-18 undergoing SEEG recording as part of the investigation of their epilepsy at Great Ormond Street Hospital for Children.
Key exclusion criteria (4 listed)
- Tuberous sclerosis
- Prior resective epilepsy surgery
- Insufficient imaging datasets for the algorithm
- 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 |
|---|---|---|
| MELD algorithm use to aid in the planning of SEEG electrode trajectoriesDuring the routine SEEG planning meetings, the planning of SEEG trajectories, including the number and location of electrodes, will follow the usual clinical pathway and be planned according to the expertise of the attending neurosurgeon, neurophysiologist and neurologist at the multidisciplinary team meeting. Once the trajectories have been planned, anonymised scans for each patient (linked to them via a unique study ID) will be run through the MELD classifier and the top 3 MELD identified lesion clusters will be considered for further implantation. These top 3 MELD classifier identified clusters will then be merged with the existing clinical plan to assess if each of the clusters are already being sampled by an SEEG electrode. If there is already an electrode in each lesion, no adjustments will be made. If there are clusters that are not being recorded from, and it is technically possible, extra electrodes (up to 3) will be added to record from these additional locations. | Procedure or surgery | MELD-assisted SEEG trajectory planning |
Primary outcome
Additional contacts in neurophysiologically defined seizure onset zone
Time frame: Baseline (During inpatient admission)
For each patient, the investigators will assess whether any of the additional electrodes (added as part of the trial to record from detected lesions) were in the neurophysiologically (SEEG) defined seizure onset zone. This will be a dichotomous yes/no outcome for each patient.
8 secondary outcomes
Pre-implantation confidence
Time frame: Baseline (During inpatient admission)
Number of electrodes added
Time frame: Baseline (During inpatient admission)
Number of electrodes added
Time frame: Baseline (During inpatient admission)
Was a MELD-identified lesion part of the SOZ (and if so how many?)
Time frame: Baseline (During inpatient admission)
Would the SOZ have been identified without MELD?
Time frame: Baseline (During inpatient admission)
Blinded neurophysiological assessment of the SOZ contacts with and without additional electrodes
Time frame: Baseline (During inpatient admission)
Putative resection boundaries with and without the additional electrodes, to be modelled by a neurosurgeon ie. a measure of whether or not this would have changed subsequent surgical strategy
Time frame: Baseline (During inpatient admission)
adverse events such as bleeding
Time frame: Baseline (During inpatient admission)
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: No. As is current good scientific practice, heavily anonymised matrices of processed data and the processing code will be made available as part of any publication. These datasets will be fully anonymised and in abstract space (ie will not contain primary MRI scan images or electrode locations) and will rather be matrices that will in no way be relatable to the patient. They will definitely not contain any patient identifiable information and will not be able to be back-processed to get identifiable information.
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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 MELD algorithm use to aid in the planning of SEEG electrode trajectories in people with Epilepsy and Epilepsy, Focal, 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 1 inclusion and 4 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?
Contact Aswin Chari, MRCS (+447726780817, aswin.chari@gosh.nhs.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Additional contacts in neurophysiologically defined seizure onset zone (time frame: Baseline (During inpatient admission)). 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.