Epilepsy, Lennox-Gastaut Syndrome, Intractable
Conditions
Keywords
Deep brain stimulation, Neurostimulation, Neuromodulation, Epilepsy, Lennox-Gastaut Syndrome
Brief summary
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
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.
Interventions
DEVICEDeep brain stimulation
Deep brain stimulation of the centromedian nucleus (bilateral)
Sponsors
Great Ormond Street Hospital for Children NHS Foundation Trust
King's College Hospital NHS Trust
University of Oxford
King's College London
University College, London
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DEVICE_FEASIBILITY
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
5 Years to 14 Years
Healthy volunteers
No
Inclusion criteria
Children enrolled in this study must: 1. Be 5-14 years of age at consent. 2. 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 3. Experience at least 10 seizures per month. 4. Have tried and not responded to two or more antiseizure medications prior to enrolment. 5. 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. 6. 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. 7. 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: 1. Have had prior deep brain stimulation insertion. 2. Have an active ('on') vagus nerve stimulator (or active within the six months prior to the baseline period). 3. Have abnormal thalamic anatomy detected on imaging that would render DBS either unsafe or unfeasible. 4. Have a bleeding disorder. 5. Have medical conditions/factors that would increase their anaesthetic risk to an unacceptable level. 6. Have a nickel allergy 7. Be pregnant 8. Participate in contact sports
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ability of the participant/parent(s)/guardian(s) to re-charge and maintain the device | Following 6-months of active stimulation | Device recharging is measured using the Picostim event logs |
| Participant completion of the study | Following 6-months of active stimulation | Completion of all study activities at study exit |
| Adverse evens | Following 6-months of active stimulation | Measured according to pre-determined device-related AEs and SAEs, as well as generic AEs and SAEs. |
| Willingness of the participants/parents/guardians for the participant to be recruited into the study and to undergo the intervention | Following 6-months of active stimulation | Consent at baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relative change in quality of life | Following 6-months of active stimulation (compared to baseline) | 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. |
| Relative change in parent-reported seizure frequency | Following 6-months of active stimulation (compared to baseline) | Measured using parent-reported diaries |
| Relative change in electrographic-recorded seizure frequency | Following 6-months of active stimulation (compared to baseline) | Measured using serial electroencephalography (EEG) |
| Relative change in seizure severity | Following 6-months of active stimulation (compared to baseline) | Measured using the Hague Seizure Severity Scoring questionnaire. Minimum score = 13; maximum score = 52; with higher seizure severity with ascending values. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Radiological correlates of neurophysiological and clinical response to CMN DBS | Following 6-months of active stimulation | Analysis of pre-trial MRI brain scan in conjunction with relative change in seizure counts measured using parent-reported diaries |
| Correlates of the scalp EEG with the intracranial recordings (local field potentials) from the DBS device. | Following 6-months of active stimulation | Analysis of local-field potentials measured from the DBS device in conjunction with data from the encephalography (EEG) data |
Countries
United Kingdom
Outcome results
None listed