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DBS in Children With Autism

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.

Condition or disease Intervention/treatment Phase
Autism Spectrum Disorder Self-Injurious Behavior Procedure: Deep Brain Stimulation Device: DBS Not Applicable

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 6 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Deep Brain Stimulation for the Treatment of Refractory Repetitive Self-Injurious Behaviour in Children With Autism Spectrum Disorder: A Pilot Project
Actual Study Start Date : August 14, 2019
Estimated Primary Completion Date : August 14, 2021
Estimated Study Completion Date : August 14, 2022
Arms and Interventions
Arm Intervention/treatment
Experimental: DBS Treatment
Deep brain stimulation of both limbic and dysfunctional reward processing circuits for treatment of repetitive self injurious behaviours in children with ASD
Procedure: Deep Brain Stimulation
Stimulation of the nucleus accumbens via 2 electrodes implanted in the brain per patient to reduce self-injurious behaviours.

Device: DBS

Use of the Medtronic DBS device. DBS device consists of 2 parts:

  1. DBS lead, a thin wire with 2 electrical contacts implanted into pre-determined brain regions, and
  2. Implantable pulse generator, a small device containing the batter and computer source placed under the skin of the chest to generate electrical pulses
Other Name: Medtronic DBS Therapy (Device # 37601)

Outcome Measures
Primary Outcome Measures :
  1. Changes in repetitive behaviour [ Time Frame: 1 year ]

    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

    1. behaviour occurs and is a mild problem
    2. behaviour occurs and is a moderate problem
    3. 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.


  2. Changes in self-injurious behaviour [ Time Frame: 1 year ]

    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

    1. somewhat relevant
    2. 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.


  3. Changes in abberant behaviour [ Time Frame: 1 year ]

    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

    1. the behaviour is a problem but slight in degree
    2. the problem is moderately serious
    3. 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.


  4. Changes in obsessive-compulsive thoughts [ Time Frame: 1 year ]

    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.


  5. Changes in quality of life [ Time Frame: 1 year ]

    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 :
  1. Changes in physical brain abnormalities [ Time Frame: 1 year ]

    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.


  2. Changes in metabolic brain abnormalities [ Time Frame: 1 year ]

    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.


  3. Changes in activity [ Time Frame: 1 year ]
    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.

  4. Type of adverse events reported in caregiver logs [ Time Frame: 1 year ]
  5. Changes in number of complications pre and post intervention will be compared. [ Time Frame: 1 year ]

Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   7 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations

Locations
Layout table for location information
Canada, Ontario
The Hospital for Sick Children Recruiting
Toronto, Ontario, Canada, M5G1X8
Contact: Lauren Siegel    416-813-7654 ext 309117    lauren.siegel@sickkids.ca   
Principal Investigator: George Ibrahim         
Sponsors and Collaborators
The Hospital for Sick Children
Tracking Information
First Submitted Date  ICMJE June 3, 2019
First Posted Date  ICMJE June 12, 2019
Last Update Posted Date March 1, 2021
Actual Study Start Date  ICMJE August 14, 2019
Estimated Primary Completion Date August 14, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 11, 2019)
  • Changes in repetitive behaviour [ Time Frame: 1 year ]
    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
    1. behaviour occurs and is a mild problem
    2. behaviour occurs and is a moderate problem
    3. 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 [ Time Frame: 1 year ]
    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
    1. somewhat relevant
    2. 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 [ Time Frame: 1 year ]
    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
    1. the behaviour is a problem but slight in degree
    2. the problem is moderately serious
    3. 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 [ Time Frame: 1 year ]
    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 [ Time Frame: 1 year ]
    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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 11, 2019)
  • Changes in physical brain abnormalities [ Time Frame: 1 year ]
    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 [ Time Frame: 1 year ]
    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 [ Time Frame: 1 year ]
    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 [ Time Frame: 1 year ]
  • Changes in number of complications pre and post intervention will be compared. [ Time Frame: 1 year ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE DBS in Children With Autism
Official Title  ICMJE Deep Brain Stimulation for the Treatment of Refractory Repetitive Self-Injurious Behaviour in Children With Autism Spectrum Disorder: A Pilot Project
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 Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Autism Spectrum Disorder
  • Self-Injurious Behavior
Intervention  ICMJE
  • Procedure: Deep Brain Stimulation
    Stimulation of the nucleus accumbens via 2 electrodes implanted in the brain per patient to reduce self-injurious behaviours.
  • Device: DBS

    Use of the Medtronic DBS device. DBS device consists of 2 parts:

    1. DBS lead, a thin wire with 2 electrical contacts implanted into pre-determined brain regions, and
    2. Implantable pulse generator, a small device containing the batter and computer source placed under the skin of the chest to generate electrical pulses
    Other Name: Medtronic DBS Therapy (Device # 37601)
Study Arms  ICMJE Experimental: DBS Treatment
Deep brain stimulation of both limbic and dysfunctional reward processing circuits for treatment of repetitive self injurious behaviours in children with ASD
Interventions:
  • Procedure: Deep Brain Stimulation
  • Device: DBS
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 11, 2019)
6
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 14, 2022
Estimated Primary Completion Date August 14, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 7 Years to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03982888
Other Study ID Numbers  ICMJE REB1000060282
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party George Ibrahim, The Hospital for Sick Children
Study Sponsor  ICMJE The Hospital for Sick Children
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account The Hospital for Sick Children
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP