Treatment to Promote Self-regulation in Children With Autism Spectrum Disorder

Repetitive Transcranial Magnetic Stimulation to Promote Helpful Self-regulatory Behaviour in Children and Youth With Autism Spectrum Disorder

This study will evaluate the feasibility of repetitive Transcranial Magnetic Stimulation (rTMS) in Autism Spectrum Disorder (ASD) with self-regulation impairment. Baseline and follow-up participant visits will include behavioral assessments of self-regulation and magnetic resonance imaging (MRI) to determine neurophysiological outcomes before and after rTMS treatment.

Study Overview

• Status: Recruiting
• Conditions: Autism Spectrum Disorder; Self-Regulation, Emotion
• Intervention / Treatment: Device: repetitive transcranial magnetic stimulation (rTMS); Other: Sham stimulation

Detailed Description

Children and youth with Autism Spectrum Disorder (ASD) often present with co-morbid impairments in self-regulation (e.g., difficulty managing their emotions) resulting in unhelpful regulatory approaches such as disruptive compulsive, aggressive and self-injurious behaviour. There is an urgent need to establish novel, precise and effective interventions that promote self-regulation and reduce disruptive behaviours. This project will collect pilot data on the effects of repetitive TMS in reducing disruptive behaviours in youth with ASD, in order to inform the design of a follow-up full-scale clinical trial. Youth with ASD who experience clinically significant difficulties with self-regulation and disruptive behaviour will be recruited. Participants will be randomized to rTMS or sham rTMS for 3 weeks. The overall feasibility of the trial will be assessed. The effect of rTMS on the brain mechanisms of self-regulation and clinical improvement in disruptive behaviours will also be measured. Neurophysiological outcomes, including changes in regional brain network activity for inhibition of behaviour, will be explored.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Deryk Beal, PhD; Phone Number: 3582 416-425-6220; Email: dbeal@hollandbloorview.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4G 1R8
      • Recruiting
      • Bloorivew Research Institute
      • Contact: Deryk Beal, PhD; Phone Number: 3582 416-425-6220; Email: dbeal@hollandbloorview.ca
      • Principal Investigator: Deryk Beal, PhD, Reg. CASLPO, CCC-SLP
      • Contact: PhD
      • Principal Investigator: Evdokia Anagnostou, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 9 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Children with a diagnosis of autism spectrum disorder and self-regulation impairment or challenges
• Able to participate in rTMS

Exclusion Criteria:

• Children with autism spectrum disorder but no co-morbid self-regulation disorders.
• Children with contraindications to TMS (history of seizures, family history of seizures, metal implants)
• Co-existing neurological conditions (epilepsy, stroke, etc.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: repetitive transcranial magnetic stimulation (rTMS); Participants will receive 15 rTMS sessions for 3 weeks.	Device: repetitive transcranial magnetic stimulation (rTMS); 30 minutes rTMS session 5 days/week for 3 weeks.
Sham Comparator: Sham; Participants will receive 15 sessions of sham stimulation for 3 weeks.	Other: Sham stimulation; 30 minutes sham stimulation 5 days/week for 3 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recruitment	Recruitment rates of 4 participants/month are achieved with a ≥ 20% response rate	Weeks 1-18
Attrition	Attrition rates of less than 10% (i.e., ≥90% of participants successfully complete assessments).	Weeks 1-18
Adherence	90% of participants who complete assessment achieve the target intensity and dose (15 rTMS sessions)	Weeks 1-18
Blinding success	Blinding of participants and their parents/caregivers and required study team members will be assessed using a Blinding Questionnaire indicating the perceived group membership (rTMS/sham)	Weeks 1-18

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Measure of Self-regulation: Emotion Dysregulation Index Reactivity and Dysphoria	Change in total score on Reactivity (0-96) and Dysphoria (0-24) scales - greater scores indicates a worse outcome	Weeks 1, 6, 18
Clinical Measure of Self-Regulation: The Response To Stress Questionnaire - Family Stress	Change in total score Response To Stress Questionnaire Family Stress Version (57-228, greater score indicates worse a outcome)	Weeks 1, 6, 18
Clinical Measure of Self-regulation: Aberrant Behaviour Checklist - Irritability Subscale	Change in total score on Aberrant Behaviour Checklist - Irritability Subscale (15-60, greater score indicates a worse outcome)	Weeks 1, 6, 18
Clinical Measure of Self-regulation: Emotional Regulation Checklist	change in total score on Emotional Regulation Checklist (24-96, low scores indicate worse outcomes)	Weeks 1, 6, 18
Overall Clinical Change	Clinical Global Impression scale - 1 item on a scale from 0-7 (a change of 0.5 indicates a clinical impact of significance)	Weeks 1, 6, 18
Inhibitory control	Go/No-Go Task Performance	Weeks 1, 6, 18
Functional brain changes (magnetic resonance imaging)	change in blood oxygen level dependent (BOLD) signal associated with go/no-go task	Weeks 1, 6, 18
Structural brain changes (magnetic resonance imaging)	Diffusion imaging - change in fractional anisotropy	Weeks 1, 6, 18

Collaborators and Investigators

• Sponsor: Holland Bloorview Kids Rehabilitation Hospital
• Collaborators: Centre for Addiction and Mental Health; University of Toronto
• Investigators: Principal Investigator: Deryk Beal, PhD, Holland Bloorview Research Institute

Publications and helpful links

General Publications

• Oberman LM, Enticott PG, Casanova MF, Rotenberg A, Pascual-Leone A, McCracken JT; TMS in ASD Consensus Group. Transcranial magnetic stimulation in autism spectrum disorder: Challenges, promise, and roadmap for future research. Autism Res. 2016 Feb;9(2):184-203. doi: 10.1002/aur.1567. Epub 2015 Nov 4.

Study record dates

Study Major Dates

• Study Start (Actual): September 22, 2022
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): February 1, 2025

Study Registration Dates

• First Submitted: January 10, 2022
• First Submitted That Met QC Criteria: February 10, 2022
• First Posted (Actual): February 11, 2022

Study Record Updates

• Last Update Posted (Actual): July 26, 2024
• Last Update Submitted That Met QC Criteria: July 25, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: MRI; rTMS; transcranial magnetic stimulation
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive
• Other Study ID Numbers: ASDSR01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No