Epilepsy, Drug ResistantDBSpostVNSNCT04181229
Deep Brain Stimulation Post Failed Vagal Nerve Stimulation
A study testing Deep brain stimulation in people with Epilepsy, Drug Resistant, run by The Hospital for Sick Children at 1 site in Canada.
Trial summary
This is a multicenter, non-blinded, patient preference comparative trial for efficacy of deep brain stimulation (DBS) on drug-resistant epilepsy compared to continued vagal nerve stimulation (VNS) optimization in children with failed VNS. Read more about this study
- Who is it for?
- Ages 8 to 18 years
- Conditions the study is for
- Epilepsy, Drug Resistant
- What is being tested?
- Deep brain stimulation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteCanada
- Study dates
- 25 Nov 2019to 30 Aug 2023
- 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 8 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Female or Male patients 8 years of age and over but not including 18 year olds.
- Diagnosis of drug-resistant epilepsy with failure after trial of two anti-epileptic medications (as defined by Kwan et al. 20093). All children screened for entry into the study will be re-diagnosed by a neurologist prior to entry.
- Failure of vagal nerve stimulation, defined as the same or increased frequency and severity of seizures at 12 months or more after instigation and optimization of therapy. Failure is defined objectively and subjectively. Objective evidence includes caregiver logs, clinician assessment, or neuromonitoring if the clinician has documented a baseline status prior to instigation of vagal nerve stimulation. Subjective measures include family or patient opinion that seizure frequency or severity has not improved.
- Parents or legal guardians, including caregivers, who are informed and able to give written consent.
- Ability to comply with all testing, follow-ups and study appointments and protocols for 12 months following the end of the duration of the study.
Who cannot join
- Substance dependence or abuse in the last 6 months, excluding caffeine and nicotine
- Any contraindication to MRI scanning. A preoperative MRI scan is essential to planning DBS and therefore any contraindication to MRI is a contraindication to enrollment in the study.
- Unwillingness or inability to return to SickKids for follow-up visits.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Deep Brain Stimulation After Failed Vagal Nerve Stimulation for the Treatment of Drug-Resistant Epilepsy in Children
This is a multicenter, non-blinded, patient preference comparative trial for efficacy of deep brain stimulation (DBS) on drug-resistant epilepsy compared to continued vagal nerve stimulation (VNS) optimization in children with failed VNS. The two conditions being compared are therefore DBS (treatment) versus VNS (control). Fifty (50) patients will be recruited and enrolled in this pilot study (25 from The Hospital for Sick Children and 50 from CHU Sainte-Justine).
Read the detailed description
For children with epilepsy that have failed pharmacological and alternative treatments (drug-resistant epilepsy; [DRE]), surgical interventions may be considered. This includes vagus nerve stimulation (VNS) and deep brain stimulation (DBS). VNS for the treatment of DRE in children is an established and widely used treatment. Unfortunately, the positive response to VNS rate (>50% reduction in seizures) is not consistent, ranging from 26-55% in pediatric epilepsy patients. In children with failed VNS, defined as no improvement in seizure control after at least 1 year of treatment, they may undergo DBS as a recommended therapy. DBS is a safe and established treatment for various childhood neurological conditions and the indications for DBS in children continue to expand. It is currently unknown which children may benefit from DBS after failed VNS.
As a patient-preference randomized trial, patients and their parents will be introduced to the options of continuing with current VNS management (control arm) or trialing DBS (treatment arm). Patients and their parents will fall into three possible groups according to preference and willingness for randomization.
- Patients with no strong preferences and consent to randomization ii) Patients with a preference, yet still consent to randomization iii) Patients who refuse randomization and opt for enrollment in a specific arm
Patients in the treatment arm will receive DBS of the centromedian nucleus. The centromedian nucleus is believed to reduce electrocortical activity in generalized epilepsy. The investigators hypothesize that stimulating this target will lead to a decrease in seizure severity and frequency in patients who have failed VNS; in comparison with patients who will have continued VNS treatment and optimization. Patients in the control arm will continue to be observed for 12 months with no change to their treatment.
- Conditions
- Epilepsy, Drug Resistant
- Being tested
- Deep brain stimulation
- Medical subject headings
- Drug Resistant Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Deep brain stimulationProcedure or surgery
Patients will receive surgical implantation of the Medtronic DBS device (Device # 37601). Two (2) electrodes will be implanted bilaterally in the centromedian nucleus.
| Study group | Role | What they receive |
|---|---|---|
| DBS Treatment | Experimental | Patients in the treatment arm will receive DBS of bilateral centromedian nucleus (2 electrodes per patient). DBS is a standard of care treatment option for drug-resistant epilepsy patients who have previously failed VNS at 12 months or more after instigation and optimization of therapy. Receives: Procedure: Deep brain stimulation |
| Continued VNS (control) | No intervention | For the control arm, the patients will be monitored for one year with the same standard assessments used for the measurement of seizure frequency and severity. No changes will be made to these patients' treatment plan. These patients will be placed on a wait list for CM-DBS treatment of seizures if that is the desire of the patient and/or their family. After the 12 months of observation, these patients can choose to undergo DBS surgery. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Seizure reduction after DBS surgery
Measured by the Class on the Engel Epilepsy Surgery Outcome Scale, where:
Class I: Free of disabling seizures IA: Completely seizure-free since surgery IB: Non disabling simple partial seizures only since surgery IC: Some disabling seizures after surgery, but free of disabline seizures for at least 2 years ID: Generalized convulsions with antiepileptic drug withdrawal only Class II: Rare disabling seizures ("almost seizure-free") IIA: Initially free of disabling seizures but has rare seizures now IIB: Rare disabling seizures since surgery IIC: More than rare disabling seiuzres after surgery, but rare seizures for at least 2 years IID: Nocturnal seizures only Class III: Worthwhile improvement IIIA: Worthwhile seiuzre reduction IIIB: Prolonged seiuzre-free intervals amounting to greater than half the follow-up period, but not less than 2 years Class IV: No worthwhile improvement IVA: Significant seizure reduction IVB: No appreciable change IVC: Seizures worse
Measured: Assessed post surgery up to 1 year
Seizure reduction after VNS surgery
Measured by the Class on the McHugh Scale, where:
Class I (80-100% reduction in seizure frequency) Class II (50-79% reduction in seizure frequency) Class III (< 50% reduction in seizure frequency) Class IV (Magnet benefit only) Class V (No improvement)
Measured: Assessed post surgery up to 1 year
Secondary outcomes (3)
Change in patient-perceived seizure severity
Measured by the Liverpool Seizure Severity Scale (LSSS) which measures patients' own perceptions of changes in seizure severity. The LSSS is rated on a 4-point likert scale, where 1 represents "always" (worse outcome) and 4 represents "never" (better outcome).
Measured: Assessed pre surgery and post surgery up to 1 year
Change in parent-perceived seizure severity
Measured by the Hague Seizure Severity (HASS) scale which measures parents' perceptions of changes in seizure severity. The HASS is measured on a 4 point likert-scale, where 1 represents "always" (worse outcome) and 4 represents "never" (better outcome).
Measured: Assessed pre surgery and post surgery up to 1 year
Change in self-reported quality of life
Measured by the Quality of Life in Epilepsy for Adolescents scale (QOLIE-AD-48), a two-part scale. Part 1 measures general health on a 5 point scale where 1 represents "excellent" (better outcome) and 5 represents "poor" (worse outcome). Part 2 measures effects of epilepsy and antiepilepsy medications on a 5 point scale where 1 represents "very often" (worse outcome) and 5 represents "never" (better outcome).
Measured: Assessed pre surgery and post surgery up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Nov 2019
- Study start25 Nov 2019
- Primary completion31 Mar 2023
- Study completion30 Aug 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Epilepsy, Drug ResistantStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Treatment arm - DBS Control arm - Continued VNS (optimization)
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Hospital for Sick Children
- Sponsor type
- University, hospital or other
- Collaborators
- St. Justine's Hospital
- Responsible party
- Principal investigator, George Ibrahim, The Hospital for Sick Children
- Investigators
- George Ibrahim, Principal investigator, The Hospital for Sick Children
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04181229
- Sponsor's protocol ID
- REB1000063803
- Acronym
- DBSpostVNS
- Status last verified
- Mar 2024
- First submitted
- 25 Nov 2019
- Last updated
- 5 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: There is not a plan to make IPD available.
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Deep Brain Stimulation After Failed Vagal Nerve Stimulation for the Treatment of Drug-Resistant Epilepsy in Children
- ClinicalTrials.gov ID
- NCT04181229
- Acronym / sponsor ID
- DBSpostVNS / REB1000063803
- Conditions
- Epilepsy, Drug Resistant
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- The Hospital for Sick ChildrenUniversity, hospital or other
- Collaborators
- St. Justine's Hospital
- Study start
- 25 Nov 2019 (actual)
- Primary completion
- 31 Mar 2023 (actual)
- Study completion
- 30 Aug 2023 (actual)
- First posted
- 29 Nov 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.
This is a multicenter, non-blinded, patient preference comparative trial for efficacy of deep brain stimulation (DBS) on drug-resistant epilepsy compared to continued vagal nerve stimulation (VNS) optimization in children with failed VNS. The two conditions being compared are therefore DBS (treatment) versus VNS (control). Fifty (50) patients will be recruited and enrolled in this pilot study (25 from The Hospital for Sick Children and 50 from CHU Sainte-Justine).
Detailed description
For children with epilepsy that have failed pharmacological and alternative treatments (drug-resistant epilepsy; [DRE]), surgical interventions may be considered. This includes vagus nerve stimulation (VNS) and deep brain stimulation (DBS). VNS for the treatment of DRE in children is an established and widely used treatment. Unfortunately, the positive response to VNS rate (>50% reduction in seizures) is not consistent, ranging from 26-55% in pediatric epilepsy patients. In children with failed VNS, defined as no improvement in seizure control after at least 1 year of treatment, they may undergo DBS as a recommended therapy. DBS is a safe and established treatment for various childhood neurological conditions and the indications for DBS in children continue to expand. It is currently unknown which children may benefit from DBS after failed VNS.
As a patient-preference randomized trial, patients and their parents will be introduced to the options of continuing with current VNS management (control arm) or trialing DBS (treatment arm). Patients and their parents will fall into three possible groups according to preference and willingness for randomization.
- Patients with no strong preferences and consent to randomization ii) Patients with a preference, yet still consent to randomization iii) Patients who refuse randomization and opt for enrollment in a specific arm
Patients in the treatment arm will receive DBS of the centromedian nucleus. The centromedian nucleus is believed to reduce electrocortical activity in generalized epilepsy. The investigators hypothesize that stimulating this target will lead to a decrease in seizure severity and frequency in patients who have failed VNS; in comparison with patients who will have continued VNS treatment and optimization. Patients in the control arm will continue to be observed for 12 months with no change to their treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Treatment arm - DBS Control arm - Continued VNS (optimization)
| Arm | Type | Receives |
|---|---|---|
| DBS Treatment | Experimental | Procedure: Deep brain stimulationPatients in the treatment arm will receive DBS of bilateral centromedian nucleus (2 electrodes per patient). DBS is a standard of care treatment option for drug-resistant epilepsy patients who have previously failed VNS at 12 months or more after instigation and optimization of therapy. |
| Continued VNS (control) | No intervention | –For the control arm, the patients will be monitored for one year with the same standard assessments used for the measurement of seizure frequency and severity. No changes will be made to these patients' treatment plan. These patients will be placed on a wait list for CM-DBS treatment of seizures if that is the desire of the patient and/or their family. After the 12 months of observation, these patients can choose to undergo DBS surgery. |
Who may qualify
- Ages
- 8 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- Female or Male patients 8 years of age and over but not including 18 year olds.
- Diagnosis of drug-resistant epilepsy with failure after trial of two anti-epileptic medications (as defined by Kwan et al. 20093). All children screened for entry into the study will be re-diagnosed by a neurologist prior to entry.
- Failure of vagal nerve stimulation, defined as the same or increased frequency and severity of seizures at 12 months or more after instigation and optimization of therapy. Failure is defined objectively and subjectively. Objective evidence includes caregiver logs, clinician assessment, or neuromonitoring if the clinician has documented a baseline status prior to instigation of vagal nerve stimulation. Subjective measures include family or patient opinion that seizure frequency or severity has not improved.
- Parents or legal guardians, including caregivers, who are informed and able to give written consent.
- Ability to comply with all testing, follow-ups and study appointments and protocols for 12 months following the end of the duration of the study.
Key exclusion criteria (3 listed)
- Substance dependence or abuse in the last 6 months, excluding caffeine and nicotine
- Any contraindication to MRI scanning. A preoperative MRI scan is essential to planning DBS and therefore any contraindication to MRI is a contraindication to enrollment in the study.
- Unwillingness or inability to return to SickKids for follow-up visits.
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 |
|---|---|---|
| Deep brain stimulationPatients will receive surgical implantation of the Medtronic DBS device (Device # 37601). Two (2) electrodes will be implanted bilaterally in the centromedian nucleus. | Procedure or surgery | DBS Treatment |
Primary outcome
Seizure reduction after DBS surgery
Time frame: Assessed post surgery up to 1 year
Measured by the Class on the Engel Epilepsy Surgery Outcome Scale, where: Class I: Free of disabling seizures IA: Completely seizure-free since surgery IB: Non disabling simple partial seizures only since surgery IC: Some disabling seizures after surgery, but free of disabline seizures for at least 2 years ID: Generalized convulsions with antiepileptic drug withdrawal only Class II: Rare disabling seizures ("almost seizure-free") IIA: Initially free of disabling seizures but has rare seizures now IIB: Rare disabling seizures since surgery IIC: More than rare disabling seiuzres after surgery, but rare seizures for at least 2 years IID: Nocturnal seizures only Class III: Worthwhile improvement IIIA: Worthwhile seiuzre reduction IIIB: Prolonged seiuzre-free intervals amounting to greater than half the follow-up period, but not less than 2 years Class IV: No worthwhile improvement IVA: Significant seizure reduction IVB: No appreciable change IVC: Seizures worse
Seizure reduction after VNS surgery
Time frame: Assessed post surgery up to 1 year
Measured by the Class on the McHugh Scale, where: Class I (80-100% reduction in seizure frequency) Class II (50-79% reduction in seizure frequency) Class III (< 50% reduction in seizure frequency) Class IV (Magnet benefit only) Class V (No improvement)
3 secondary outcomes
Change in patient-perceived seizure severity
Time frame: Assessed pre surgery and post surgery up to 1 year
Change in parent-perceived seizure severity
Time frame: Assessed pre surgery and post surgery up to 1 year
Change in self-reported quality of life
Time frame: Assessed pre surgery and post surgery up to 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2024.
- Individual participant dataSharing planned: No. There is not a plan to make IPD available.
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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.
George Ibrahim principal investigator
The Hospital for Sick Children
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Deep brain stimulation in people with Epilepsy, Drug Resistant, run by The Hospital for Sick Children at 1 site in Canada.
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: finished, as of the sponsor's last update on 5 Mar 2024. 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 Canada. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Seizure reduction after DBS surgery (time frame: Assessed post surgery up to 1 year). 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 5 Mar 2024.