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Deep Brain Stimulation Post Failed Vagal Nerve Stimulation (DBSpostVNS)

Primary Purpose

Epilepsy, Drug Resistant

Status
Recruiting
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
Deep brain stimulation
Sponsored by
The Hospital for Sick Children
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Epilepsy, Drug Resistant

Eligibility Criteria

8 Years - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Female or Male patients 8 years of age and over but not including 18 year olds.
  2. 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.
  3. 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.
  4. Parents or legal guardians, including caregivers, who are informed and able to give written consent.
  5. 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.

Exclusion Criteria:

  1. Substance dependence or abuse in the last 6 months, excluding caffeine and nicotine
  2. 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.
  3. Unwillingness or inability to return to SickKids for follow-up visits.

Sites / Locations

  • The Hospital for Sick ChildrenRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

DBS Treatment

Continued VNS (control)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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
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)

Secondary Outcome Measures

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).
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).
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).

Full Information

First Posted
November 25, 2019
Last Updated
May 11, 2022
Sponsor
The Hospital for Sick Children
Collaborators
St. Justine's Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04181229
Brief Title
Deep Brain Stimulation Post Failed Vagal Nerve Stimulation
Acronym
DBSpostVNS
Official Title
Deep Brain Stimulation After Failed Vagal Nerve Stimulation for the Treatment of Drug-Resistant Epilepsy in Children
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Recruiting
Study Start Date
November 25, 2019 (Actual)
Primary Completion Date
March 31, 2023 (Anticipated)
Study Completion Date
March 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The Hospital for Sick Children
Collaborators
St. Justine's Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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. 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. i) 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Epilepsy, Drug Resistant

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Treatment arm - DBS Control arm - Continued VNS (optimization)
Masking
None (Open Label)
Allocation
Randomized
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
DBS Treatment
Arm Type
Experimental
Arm Description
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.
Arm Title
Continued VNS (control)
Arm Type
No Intervention
Arm Description
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.
Intervention Type
Procedure
Intervention Name(s)
Deep brain stimulation
Intervention Description
Patients will receive surgical implantation of the Medtronic DBS device (Device # 37601). Two (2) electrodes will be implanted bilaterally in the centromedian nucleus.
Primary Outcome Measure Information:
Title
Seizure reduction after DBS surgery
Description
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
Time Frame
Assessed post surgery up to 1 year
Title
Seizure reduction after VNS surgery
Description
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)
Time Frame
Assessed post surgery up to 1 year
Secondary Outcome Measure Information:
Title
Change in patient-perceived seizure severity
Description
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).
Time Frame
Assessed pre surgery and post surgery up to 1 year
Title
Change in parent-perceived seizure severity
Description
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).
Time Frame
Assessed pre surgery and post surgery up to 1 year
Title
Change in self-reported quality of life
Description
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).
Time Frame
Assessed pre surgery and post surgery up to 1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
8 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lauren Siegel
Phone
416-813-7654
Ext
309117
Email
lauren.siegel@sickkids.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
George Ibrahim
Organizational Affiliation
The Hospital for Sick Children
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Hospital for Sick Children
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G1X8
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lauren Siegel
Phone
416-813-7654
Ext
309117
Email
lauren.siegel@sickkids.ca
First Name & Middle Initial & Last Name & Degree
George Ibrahim

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
There is not a plan to make IPD available.

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Deep Brain Stimulation Post Failed Vagal Nerve Stimulation

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