rTMS to Improve Motor Function in Autism ((AMBLE Autism))

Modulating Plasticity in the Motor Cortex Using Repetitive Transcranial Magnetic Stimulation to Improve Motor Function in Autism Spectrum Disorder

In the current project, investigators have two main goals: i) Testing whether an excessive plasticity, i.e. hyperplasticity in the motor cortex underlies motor function difficulties in autistic adults, and ii) Using repetitive Transcranial Magnetic Stimulation (rTMS) with autistic adults to examine whether resulting reduced hyperplasticity in the motor cortex will be associated with clinical improvements in the motor function.

Study Overview

• Status: Recruiting
• Conditions: Autism Spectrum Disorder; Motor Activity
• Intervention / Treatment: Device: Active rTMS to the motor cortex; Device: Sham rTMS to the motor cortex

Detailed Description

Autism spectrum disorder (ASD) is a very common developmental condition, yet the cause remains unknown and effective treatment options to improve outcomes remain limited. Most autistic adults experience significant motor function difficulties involving balance, posture, coordination, and strength that negatively affect their quality of life, social interaction, confidence and daily functioning. Therefore, such difficulties remain an important treatment target. However, there are no known effective clinical interventions for such difficulties. Investigators previously showed that the part of the brain that controls motor movements, i.e. motor cortex, showed hyperplasticity, as assessed by theta-burst magnetic brain stimulation (TBS), in autistic adults. Hyperplasticity may adversely affect brain health and behavior. Investigators also previously found that rTMS may reduce such hyperplasticity in the motor cortex in autistic adults.

In this project, 100 autistic adults with significant motor function difficulties and 50 neurotypical (NT) controls matched 2:1 based on age, sex, and IQ will be recruited. At the Centre for Addiction and Mental Health, Toronto, each autistic adult's participation will consist of eight visits, while each NT adult's participation will include two visits.

All participants, both autistic and NT, will undergo clinical, adaptive, and motor function assessments during their first visit (lasting approximately 3 hours) and a pre- and post-intermittent-TBS (iTBS) session, paired with electroencephalography (EEG), to induce and assess plasticity in the left or right motor cortex (depending on handedness) during their second visit (lasting approximately 3 hours). Based on the preliminary evidence that rTMS reduces hyperplasticity in the motor cortex in autistic adults, the investigators will then use a randomized, double-blind, sham-controlled design for bilateral 3-session rTMS on the motor cortex. Autistic participants will be randomized (1:1, sex-stratified) to receive either active or sham rTMS (150 trains of 40 pulses with an inter-train interval of 25 seconds, delivered at 90% of the resting motor threshold for both conditions) three days a week (approximately 1.5 hours each), from their third to fifth visits (total of 3 sessions). Assessment of motor and adaptive function, and plasticity in the motor cortex will be repeated the next day, one week (seventh visit), and four weeks (eighth visit) after the last rTMS session (i.e. 3rd rTMS session).

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Pushpal Desarkar, MD; Phone Number: 32726 4165358501; Email: Pushpal.Desarkar@camh.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M6J 1H4
      • Recruiting
      • Center for Addiction and Mental Health (CAMH)
      • Contact: Pushpal Desarkar, MD; Phone Number: 32726 4165358501; Email: Pushpal.Desarkar@camh.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

ASD or control participants must meet all of the inclusion criteria to eligible for this study:

1. Aged between 18 and 40 years old. 40 years is chosen as the cut-off because of the report of high rates of Parkinsonism in autistic adults > 39years;
2. Have IQ>70;
3. Are able to read, write and communicate effectively in English;
4. Are able to provide informed consent. We will recruit only intellectually-able autistic adults. The intellectual ability will be determined using WASI-II. The ability to provide consent will be determined using clinical assessment.
5. Have no prior history of seizure;
6. Must sign and date the informed consent form;
7. Stated willingness to comply with all study procedures;
8. Agreement to adhere to Lifestyle Considerations, that is: refrain from consumption of alcohol, tobacco, marijuana, or caffeine on the day of study visits.

All ASD participants:

1. Will have DSM-5 diagnosis of ASD without intellectual disability, confirmed by clinical assessment and the Autism Diagnostic Observation Schedule - 2 (ADOS-2);
2. Will have significant motor function difficulties defined as a standard composite score <40 (i.e., >1 standard deviation below the mean) on either fine or gross motor composite scores of the Bruininks-Oseretsky Test of Motor Proficiency, Second Edition or BOT-2;
3. Are clinically stable as determined by clinical assessment, with no medication changes over the past 4 weeks. Given the high variability of handedness in ASD, we will include participants with left, right or mixed handedness.

Exclusion Criteria:

ASD or control participants will be excluded if they experience/have:

1. Current pregnancy;
2. Current or past history of co-morbid medical condition that may require urgent medical intervention;
3. DSM-5 substance use disorder (other than tobacco) within the past 6 months; however, all participants will be asked to refrain from smoking or taking caffeine four hours prior to the iTBS session;
4. Significant hearing or visual impairment interfering with the ability to read or hear instructions;
5. Significantly debilitating medical or neurologic illness (e.g., encephalitis, aneurysms, tumors, central nervous system infections), or acute or unstable medical illnesses as determined by project physician (e.g., uncontrolled diabetes);
6. Metal implants or a pace-maker;
7. Prior rTMS treatment;

In addition, ASD participants will be excluded if they report taking benzodiazepines or anticonvulsants currently.

NT controls will be excluded if they have:

1. Presence of psychopathology other than specific phobia, as screened by Personality Assessment Inventory and;
2. A known diagnosis of Pervasive Developmental Disorder or ASD among any biologically related family members.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active rTMS; Autistic adults receiving active rTMS to the motor cortex.	Device: Active rTMS to the motor cortex; Active bilateral repetitive transcranial magnetic stimulation to the motor cortex
Sham Comparator: Sham rTMS; Autistic adults receiving sham rTMS to the motor cortex.	Device: Sham rTMS to the motor cortex; Sham bilateral repetitive transcranial magnetic stimulation to the motor cortex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in motor cortical plasticity using motor evoked potentials (MEPs) in autistic adults following rTMS.	Plasticity will be indexed by the duration of facilitation of motor evoked potentials (MEPs) amplitude, i.e. the time for the MEP amplitude to return to baseline values following iTBS.	Plasticity in the motor cortex will be evaluated at baseline, the day after the final rTMS session, and again at 1 and 4 weeks after the last rTMS session.
Changes in motor function in autistic adults following rTMS.	Bruininks-Oseretsky Test of Motor Proficiency, Second Edition (BOT-2) will be used to assess motor function. The total motor composite score will be used as the primary measure of motor function. A higher score on BOT-2 indicates better motor performance.	Motor function will be assessed at baseline, the day after the final rTMS, and again at 1 and 4 weeks after the last rTMS session.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in motor cortical plasticity using cortical evoked activity (CEA) in autistic adults following rTMS.	A secondary measure of plasticity will be indexed by the maximum post-iTBS/pre-iTBS cortical evoked activity (CEA) ratio. CEA will be defined as the area under rectified curve for averaged electroencephalography (EEG) recordings in the electrode over motor cortex between 50-275 millisecond post-stimulus.	Plasticity in the motor cortex will be evaluated at baseline, the day after the final rTMS, and again at 1 and 4 weeks after the last rTMS session.
Changes in the adaptive daily living skills in autistic adults following rTMS.	The daily living skills domain of Adaptive Behavior Assessment System-3rd edition will be used to assess adaptive daily living skills. A higher score represents better adaptive skills.	Adaptive daily living skills will be assessed at baseline, the day after the final rTMS, and again at 1 and 4 weeks after the last rTMS session.

Collaborators and Investigators

• Sponsor: Centre for Addiction and Mental Health

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2024
• Primary Completion (Estimated): April 30, 2029
• Study Completion (Estimated): June 30, 2029

Study Registration Dates

• First Submitted: June 13, 2024
• First Submitted That Met QC Criteria: July 5, 2024
• First Posted (Actual): July 12, 2024

Study Record Updates

• Last Update Posted (Estimated): November 14, 2025
• Last Update Submitted That Met QC Criteria: November 13, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Autism; Transcranial Magnetic Stimulation; Electroencephalography; Motor Cortex; Repetitive Transcranial Magnetic Stimulation; Motor Function
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Behavior; Autism Spectrum Disorder; Autistic Disorder; Motor Activity
• Other Study ID Numbers: 2023/180

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No