Children's Adaptive Deep Brain Stimulation for Epilepsy Trial (CADET): Pilot

Study Overview
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Brief Summary
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The CADET Pilot will investigate the safety and feasibility of deep brain stimulation (DBS) to treat children with Lennox-Gastaut syndrome using a novel DBS device (Picostim DyNeuMo-1). Following a 30-day preoperative/baseline assessment phase, all children will have a neurosurgical procedure to implant the device. Implantation will be followed by a 30-day phase of no stimulation (the device is off / inactive) and then a six-month phase of active stimulation (the device is on / active).

Detailed Description
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The CADET pilot will be a single-arm, multi-site, interventional clinical trial. This design has been chosen since this is a feasibility and safety trial in a small number of patients and thus does not primarily aim to determine efficacy. In this pilot clinical trial, four children with drug-resistant LGS will undergo bilateral CMN DBS. Following the DBS insertion, all children will undergo one month of inactive ('off') DBS in order to allow the lesioning effect of electrode implantation to dissipate. Thereafter, children will receive active ('on') DBS therapy with standard stimulation parameters for six-months. Following the 'on' phase of the trial, the child will then transition into continuing clinical care and will have their stimulation parameters altered according to clinical evaluation.

Official Title
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Children's Adaptive Deep Brain Stimulation for Epilepsy Trial (CADET): Pilot

Conditions
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Epilepsy, Lennox-Gastaut Syndrome, Intractable

Intervention / Treatment
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* Device: Deep brain stimulation


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: Children enrolled in this study must: Be 5-14 years of age at consent. Have a diagnosis of Lennox-Gastaut Syndrome, as determined by: Slow (<3.0Hz) spike-and-wave pattern and/or fast wave pattern (tonic seizures) on EEG for at least six-months months prior to the enrolment into the baseline period History of drop seizures (tonic, atonic, or tonic-clonic) for at least six-months prior to the enrolment into the baseline period Experience at least 10 seizures per month. Have tried and not responded to two or more antiseizure medications prior to enrolment. Be taking one or more anti-seizure medication(s) at a stable dose for at least the four weeks prior and have a parent/guardian(s) who is willing for their child's maintenance anti-seizure drugs to be unaltered for the trial duration. If on a ketogenic diet, have been established on a stable ketogenic diet for at least 12 weeks prior to screening and the parent/guardian(s) to be willing for child to stay on a stable ketogenic for the duration of the trial. Have a parent/guardian(s) who is willing and able to comply with all the requirements of the study, including the completion of the seizure diary and periodic device charging. ------------------------------- EXCLUSION CRITERIA: Children enrolled in this study must not: Have had prior deep brain stimulation insertion. Have an active ('on') vagus nerve stimulator (or active within the six months prior to the baseline period). Have abnormal thalamic anatomy detected on imaging that would render DBS either unsafe or unfeasible. Have a bleeding disorder. Have medical conditions/factors that would increase their anaesthetic risk to an unacceptable level. Have a nickel allergy Be pregnant Participate in contact sports

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 14 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Device Feasibility
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Deep brain stimulation<br>Deep Brain stimulation using a novel device: Bioinduction Picostim Deep Brain Stimulation system. | Device: Deep brain stimulation<br>* Deep brain stimulation of the centromedian nucleus (bilateral)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse evens | Measured according to pre-determined device-related AEs and SAEs, as well as generic AEs and SAEs. | Following 6-months of active stimulation | 
| Willingness of the participants/parents/guardians for the participant to be recruited into the study and to undergo the intervention | Consent at baseline | Following 6-months of active stimulation | 
| Participant completion of the study | Completion of all study activities at study exit | Following 6-months of active stimulation | 
| Ability of the participant/parent(s)/guardian(s) to re-charge and maintain the device | Device recharging is measured using the Picostim event logs | Following 6-months of active stimulation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative change in parent-reported seizure frequency | Measured using parent-reported diaries | Following 6-months of active stimulation (compared to baseline) | 
| Relative change in electrographic-recorded seizure frequency | Measured using serial electroencephalography (EEG) | Following 6-months of active stimulation (compared to baseline) | 
| Relative change in seizure severity | Measured using the Hague Seizure Severity Scoring questionnaire. Minimum score = 13; maximum score = 52; with higher seizure severity with ascending values. | Following 6-months of active stimulation (compared to baseline) | 
| Relative change in quality of life | Measured on the Pediatric Quality of Life Inventory (PedsQL) questionnaire. The minimum score is 0 and the maximum score is 100, with improving quality of life with ascending values. | Following 6-months of active stimulation (compared to baseline) | 
| Relative change in quality of life | Measured on the Impact of Pediatric Epilepsy Scale (IPES) questionnaires. The minimum score is 0 and the maximum score is 100, with improving quality of life with ascending values. | Following 6-months of active stimulation (compared to baseline) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Deep brain stimulation, Neurostimulation, Neuromodulation, Epilepsy, Lennox-Gastaut Syndrome