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Deep Brain Stimulation in Children With Autism

Primary Purpose

Autism Spectrum Disorder, Self-Injurious Behavior

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

About this trial

This is an interventional treatment trial for Autism Spectrum Disorder focused on measuring deep brain stimulation

Eligibility Criteria

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

Inclusion Criteria:

  • Female or Male patients between age 7-18
  • Diagnosis of Autism Spectrum Disorder (as defined by the DSM-5).
  • Failure or non eligibility of medical therapy with ongoing repetitive self-injurious behaviours, at 6 months or more after instigation of therapy. Failure is defined as a lack of improvement in self-injurious behaviours, as documented by objective evidence, including caregiver logs or clinician assessment, if the clinician has documented a baseline status prior to instigation of the medical therapy.
  • Diagnosis of secondary stereotypies, based on clinical assessment of the treating physicians with evidence of self-injury, documented in the patient records.
  • Parents or legal guardians, including caregivers, informed and able to give written consent.
  • Able 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 or PET scanning
  • Likely to relocate away from the study site or move during the study's one year duration
  • Presence of cardiac arrhythmias, or other cardiac, respiratory, renal or endocrine conditions that will result in significant risk from a surgical procedure.
  • Pregnancy
  • Unable to communicate adequately in English in order to complete the baseline and follow-up questionnaires.

Sites / Locations

  • The Hospital for Sick ChildrenRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

DBS Treatment

Arm Description

Deep brain stimulation of both limbic and dysfunctional reward processing circuits for treatment of repetitive self injurious behaviours in children with ASD

Outcomes

Primary Outcome Measures

Changes in repetitive behaviour
The Repetitive Behavior Scale-Revised (RBS-R; Bodfish, Symons, Parker & Lewis, 2000) will be used to measure changes in repetitive behaviour pre and post intervention. The following sub-scales will be used: Steretyped behaviour subscale Self-injurious behaviour subscale Compulsive behaviour subscale Ritualistic behaviour subscale Sameness behaviour subscale Restricted behaviour subscale All subscales are scored from 0-3 as follows: 0 = behaviour does not occur behaviour occurs and is a mild problem behaviour occurs and is a moderate problem behaviour occurs and is a severe problem Where a higher number indicates increased repetitive behaviour. Subscores are totaled and then an overall score is calculated. Measure will be completed at baseline (pre-surgery), weekly from weeks 2-6 post-surgery, bi-weekly from weeks 7-10 post surgery, monthly from weeks 11-51 post-surgery, and 1 year post surgery.
Changes in self-injurious behaviour
The Inventory of Statements about Self-Injury (ISAS; Klonsky & Olino, 2008) will be used to measure changes in self-injurious behaviour pre and post intervention. The scale is scored from 0-2 as follows: 0= not relevant somewhat relevant very relavant Where a higher number indicates increased self-injurious behaviour. Questions are scored and totaled. Measure will be completed at baseline (pre-surgery), weekly from weeks 2-6 post-surgery, bi-weekly from weeks 7-10 post surgery, monthly from weeks 11-51 post-surgery, and 1 year post surgery.
Changes in abberant behaviour
The Aberrant Behavior Checklist (Aman, Singh, Stewart & Field, 1985) will be used to measure changes in the extent that abberant behaviour is a problem pre and post intervention. The scale is scored from 0-3 as follows: 0= not at all a problem the behaviour is a problem but slight in degree the problem is moderately serious the problem is severe in degree Where the higher number indicates the behaviour is problematic. Questions are scored and totaled. Measure will be completed at baseline (pre-surgery), weekly from weeks 2-6 post-surgery, bi-weekly from weeks 7-10 post surgery, monthly from weeks 11-51 post-surgery, and 1 year post surgery.
Changes in obsessive-compulsive thoughts
The Yale-Brown Obsessive Compulsive Scale (Y-BOCS; Goodman, Price, Rasmussen,1989) will be used to measure changes in the amount of interference of unwanted ideas, images, or impulses pre and post intervention. The scale is scored from 0-4, where 0 represents minimal interference and 4 represents substantial interference. Questions are scored and totaled. Measure will be completed at baseline (pre-surgery), weekly from weeks 2-6 post-surgery, bi-weekly from weeks 7-10 post surgery, monthly from weeks 11-51 post-surgery, and 1 year post surgery.
Changes in quality of life
The Paediatric Quality of Life Inventory (PedsQL v. 4.0) will be used to measure changes in self-reported quality of life pre and post intervention. The statements are scored from 0-4 as follows: 0= it is never a problem 1 = it is almost never a problem 2= it is sometimes a problem 3 = it is often a problem 4= it is almost always a problem Where a higher score indicates the statement is a problem. All items are scored and totaled. Measure will be completed at baseline (pre-surgery), weekly from weeks 2-6 post-surgery, bi-weekly from weeks 7-10 post surgery, monthly from weeks 11-51 post-surgery, and 1 year post surgery.

Secondary Outcome Measures

Changes in physical brain abnormalities
MR images will be analyzed pre and post intervention for the following to assess physical abnormalities of the brain, including type (focal cortical dysplasia, tumor, hippocampal sclerosis, hypothalamic hamartoma, gliosis, brain atrophy), side of abnormalities (left/right/ bilateral), and location (frontal, temporal, sylvian, parietal, occipital, multilobar). MRI data will be collected at baseline, 6 weeks post-surgery, and 1 year post-surgery.
Changes in metabolic brain abnormalities
FDG-PET scans will be analyzed to measure changes in neurometabolism pre and post intervention, specifically indications of hypermetabolism in the frontal lobes, hippocampus, and lentiform nucleus. FDG-PET data will be collected at baseline, 6 weeks post-surgery, and 1 year post-surgery.
Changes in activity
Changes in activity pre and post intervention will be measured using the Actiwatch Spectrum, Phillips Respironics, Bend, OR. Actigraphy is the continuous measurement of an individual's movement. Actigraph data will be collected at baseline, 6 weeks post-surgery, and 1 year post-surgery. Actigraph data will be analyzed using MATLAB (Mathworks, Natick, MA). Measures analyzed will be maximum and minimum value amplitudes, peak to peak, variance, entropy fast fourier transform, discrete cosine function, z-transform, bispectrum.
Type of adverse events reported in caregiver logs
Changes in number of complications pre and post intervention will be compared.

Full Information

First Posted
June 3, 2019
Last Updated
October 24, 2022
Sponsor
The Hospital for Sick Children
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1. Study Identification

Unique Protocol Identification Number
NCT03982888
Brief Title
Deep Brain Stimulation in Children With Autism
Official Title
Deep Brain Stimulation for the Treatment of Refractory Repetitive Self-Injurious Behaviour in Children With Autism Spectrum Disorder: A Pilot Project
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
August 14, 2019 (Actual)
Primary Completion Date
August 14, 2023 (Anticipated)
Study Completion Date
August 14, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The Hospital for Sick Children

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
The purpose of this study is to evaluate the safety and possible effectiveness of deep brain stimulation (DBS) of the nucleus accumbens in children with autism spectrum disorder and treatment-refractory, repetitive self-injurious behavior. Six (6) patients will be recruited and enrolled in this pilot study and study duration for each patient will be one (1) year. All will undergo surgical implantation of the Medtronic DBS system and will receive stimulation of the nucleus accumbens (2 electrodes per patient).This will be an open, non-blinded, non-randomized, pilot, phase I trial.Expected study duration is 36 months.
Detailed Description
This is a phase I, non-blinded, non-randomized, pilot trial for safety and efficacy of deep brain stimulation for medically-refractory, repetitive self-injurious behaviours in children with ASD (i.e. secondary stereotypies). The trial will be conducted in compliance with the protocol, GCP and the applicable regulatory requirement(s). Patients who meet inclusion and exclusion criteria will be identified and recruited the Neurosurgical Clinic at The Hospital for Sick Children. The study will proceed according to the schedule laid out below, and both patients and treating team will be aware of all treatment parameters at all times. Six (6) subjects will be enrolled in this study and study duration for each patient will be one (1) year. Previous phase I trials of DBS in psychiatric and Alzheimer's Disease populations have utilized 6 subjects per surgical target. Such a number is sufficient to demonstrate initial safety, as well as feasibility and clinical effectiveness.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Autism Spectrum Disorder, Self-Injurious Behavior
Keywords
deep brain stimulation

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
DBS Treatment
Arm Type
Experimental
Arm Description
Deep brain stimulation of both limbic and dysfunctional reward processing circuits for treatment of repetitive self injurious behaviours in children with ASD
Intervention Type
Procedure
Intervention Name(s)
Deep Brain Stimulation
Intervention Description
Stimulation of the nucleus accumbens via 2 electrodes implanted in the brain per patient to reduce self-injurious behaviours.
Intervention Type
Device
Intervention Name(s)
DBS
Other Intervention Name(s)
Medtronic DBS Therapy (Device # 37601)
Intervention Description
Use of the Medtronic DBS device. DBS device consists of 2 parts: DBS lead, a thin wire with 2 electrical contacts implanted into pre-determined brain regions, and Implantable pulse generator, a small device containing the batter and computer source placed under the skin of the chest to generate electrical pulses
Primary Outcome Measure Information:
Title
Changes in repetitive behaviour
Description
The Repetitive Behavior Scale-Revised (RBS-R; Bodfish, Symons, Parker & Lewis, 2000) will be used to measure changes in repetitive behaviour pre and post intervention. The following sub-scales will be used: Steretyped behaviour subscale Self-injurious behaviour subscale Compulsive behaviour subscale Ritualistic behaviour subscale Sameness behaviour subscale Restricted behaviour subscale All subscales are scored from 0-3 as follows: 0 = behaviour does not occur behaviour occurs and is a mild problem behaviour occurs and is a moderate problem behaviour occurs and is a severe problem Where a higher number indicates increased repetitive behaviour. Subscores are totaled and then an overall score is calculated. Measure will be completed at baseline (pre-surgery), weekly from weeks 2-6 post-surgery, bi-weekly from weeks 7-10 post surgery, monthly from weeks 11-51 post-surgery, and 1 year post surgery.
Time Frame
1 year
Title
Changes in self-injurious behaviour
Description
The Inventory of Statements about Self-Injury (ISAS; Klonsky & Olino, 2008) will be used to measure changes in self-injurious behaviour pre and post intervention. The scale is scored from 0-2 as follows: 0= not relevant somewhat relevant very relavant Where a higher number indicates increased self-injurious behaviour. Questions are scored and totaled. Measure will be completed at baseline (pre-surgery), weekly from weeks 2-6 post-surgery, bi-weekly from weeks 7-10 post surgery, monthly from weeks 11-51 post-surgery, and 1 year post surgery.
Time Frame
1 year
Title
Changes in abberant behaviour
Description
The Aberrant Behavior Checklist (Aman, Singh, Stewart & Field, 1985) will be used to measure changes in the extent that abberant behaviour is a problem pre and post intervention. The scale is scored from 0-3 as follows: 0= not at all a problem the behaviour is a problem but slight in degree the problem is moderately serious the problem is severe in degree Where the higher number indicates the behaviour is problematic. Questions are scored and totaled. Measure will be completed at baseline (pre-surgery), weekly from weeks 2-6 post-surgery, bi-weekly from weeks 7-10 post surgery, monthly from weeks 11-51 post-surgery, and 1 year post surgery.
Time Frame
1 year
Title
Changes in obsessive-compulsive thoughts
Description
The Yale-Brown Obsessive Compulsive Scale (Y-BOCS; Goodman, Price, Rasmussen,1989) will be used to measure changes in the amount of interference of unwanted ideas, images, or impulses pre and post intervention. The scale is scored from 0-4, where 0 represents minimal interference and 4 represents substantial interference. Questions are scored and totaled. Measure will be completed at baseline (pre-surgery), weekly from weeks 2-6 post-surgery, bi-weekly from weeks 7-10 post surgery, monthly from weeks 11-51 post-surgery, and 1 year post surgery.
Time Frame
1 year
Title
Changes in quality of life
Description
The Paediatric Quality of Life Inventory (PedsQL v. 4.0) will be used to measure changes in self-reported quality of life pre and post intervention. The statements are scored from 0-4 as follows: 0= it is never a problem 1 = it is almost never a problem 2= it is sometimes a problem 3 = it is often a problem 4= it is almost always a problem Where a higher score indicates the statement is a problem. All items are scored and totaled. Measure will be completed at baseline (pre-surgery), weekly from weeks 2-6 post-surgery, bi-weekly from weeks 7-10 post surgery, monthly from weeks 11-51 post-surgery, and 1 year post surgery.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Changes in physical brain abnormalities
Description
MR images will be analyzed pre and post intervention for the following to assess physical abnormalities of the brain, including type (focal cortical dysplasia, tumor, hippocampal sclerosis, hypothalamic hamartoma, gliosis, brain atrophy), side of abnormalities (left/right/ bilateral), and location (frontal, temporal, sylvian, parietal, occipital, multilobar). MRI data will be collected at baseline, 6 weeks post-surgery, and 1 year post-surgery.
Time Frame
1 year
Title
Changes in metabolic brain abnormalities
Description
FDG-PET scans will be analyzed to measure changes in neurometabolism pre and post intervention, specifically indications of hypermetabolism in the frontal lobes, hippocampus, and lentiform nucleus. FDG-PET data will be collected at baseline, 6 weeks post-surgery, and 1 year post-surgery.
Time Frame
1 year
Title
Changes in activity
Description
Changes in activity pre and post intervention will be measured using the Actiwatch Spectrum, Phillips Respironics, Bend, OR. Actigraphy is the continuous measurement of an individual's movement. Actigraph data will be collected at baseline, 6 weeks post-surgery, and 1 year post-surgery. Actigraph data will be analyzed using MATLAB (Mathworks, Natick, MA). Measures analyzed will be maximum and minimum value amplitudes, peak to peak, variance, entropy fast fourier transform, discrete cosine function, z-transform, bispectrum.
Time Frame
1 year
Title
Type of adverse events reported in caregiver logs
Time Frame
1 year
Title
Changes in number of complications pre and post intervention will be compared.
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
7 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Female or Male patients between age 7-18 Diagnosis of Autism Spectrum Disorder (as defined by the DSM-5). Failure or non eligibility of medical therapy with ongoing repetitive self-injurious behaviours, at 6 months or more after instigation of therapy. Failure is defined as a lack of improvement in self-injurious behaviours, as documented by objective evidence, including caregiver logs or clinician assessment, if the clinician has documented a baseline status prior to instigation of the medical therapy. Diagnosis of secondary stereotypies, based on clinical assessment of the treating physicians with evidence of self-injury, documented in the patient records. Parents or legal guardians, including caregivers, informed and able to give written consent. Able 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 or PET scanning Likely to relocate away from the study site or move during the study's one year duration Presence of cardiac arrhythmias, or other cardiac, respiratory, renal or endocrine conditions that will result in significant risk from a surgical procedure. Pregnancy Unable to communicate adequately in English in order to complete the baseline and follow-up questionnaires.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
George M Ibrahim, MD
Phone
416-813-6425
Email
george.ibrahim@sickkids.ca
First Name & Middle Initial & Last Name or Official Title & Degree
Carolina Gorodetsky, MD
Phone
416-813-6428
Email
carolina.gorodetsky@sickkids.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
George Ibrahim, MD
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
MyLoi H Huynh
Phone
416-813-7654
Ext
309117
Email
myloi.huynh@sickkids.ca
First Name & Middle Initial & Last Name & Degree
George Ibrahim

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
35109924
Citation
Yan H, Siegel L, Breitbart S, Gorodetsky C, Fasano A, Rahim A, Loh A, Kulkarni AV, Ibrahim GM. An open-label prospective pilot trial of nucleus accumbens deep brain stimulation for children with autism spectrum disorder and severe, refractory self-injurious behavior: study protocol. Pilot Feasibility Stud. 2022 Feb 2;8(1):24. doi: 10.1186/s40814-022-00988-3.
Results Reference
derived

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Deep Brain Stimulation in Children With Autism

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