Intermittent Theta-Burst Stimulation to Target Irritability in Adults With ASD

This study aims to demonstrate the feasibility, tolerability, safety and preliminary efficacy of 6 weeks of fMRI-guided iTBS delivered to personalized regions of the prefrontal cortex (PFC) in adults with ASD in reducing irritability in adults with ASD.

Study Overview

• Status: Withdrawn
• Conditions: Autism Spectrum Disorder
• Intervention / Treatment: Device: Intermittent theta-burst stimulation (iTBS)

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years to 55 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Diagnosis of ASD or Asperger's based on DSM-5 criteria as confirmed by a qualified clinician (including Dr. Fung), and if necessary the administration of Autism Diagnostic Interview-Revised (ADI-R) and/or Autism Diagnostic Observation Schedule-Generic (ADOS-G)
2. Age 22 to 55.
3. Adults who are physically healthy.
4. No significant current psychosocial stressors per history.
5. Full scale IQ > 50.
6. ABC-I score of 18 or greater.
7. if the participant is taking medication, they must be stable on this medication regiment for at least 4 weeks prior to baseline and agree to stay on these medications for the duration of the trial

Exclusion Criteria:

(f) Pre-term birth (<34 weeks' gestation) (g) Low birth weight (<2000 g). (h) DSM-5 diagnosis of other severe psychiatric disorder such as bipolar disorder or schizophrenia.

(i) Current use of benzodiazepines. (j) Use of other medications that modulate the GABA(A) receptor within 4 weeks of scanning (8 weeks for fluoxetine).

(k) History of alcoholism or substance abuse. (l) Active medical problems such as unstable seizures, congenital heart disease, endocrine disorders.

(m) Significant sensory impairments such as blindness or deafness. (n) Contraindication for MRI. (o) Pregnancy. (p) evidence of genetic syndrome.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active intermittent theta-burst stimulation (iTBS); 6 weeks of iTBS delivered at 80% resting motor threshold will be delivered to personalized regions in the prefrontal cortex based on each individual's functional connectivity.	Device: Intermittent theta-burst stimulation (iTBS); Non-invasive brain stimulation technique

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Aberrant Behavior Checklist-irritability subscale (ABC-I)	A parent/caregiver/clinician completed checklist (58-item) with an irritability subscale (15-item). Each item has a maximum score of 3, meaning that the irritability subscale has a maximum score of 45 and minimum score of 0. Higher scores indicate higher levels of irritability.	Change across time: Baseline minus immediately after final treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Irritability Questionnaire	A 21-item self-report measure of irritability. Each item is rated on how often (Never=0 to Most of the time=4) and the intensity (Not at all=0, Very much so=4) at which they occur.	Baseline, every week of treatment (1-6), immediately after treatment, one month after treatment.
Self-injury questionnaire (SIQ)	Self-report measure of self-injury, maximum 60 questions but participants only answer relevant questions. Five types of self-injurious behaviors are checked: scratching, bruising, cutting, burning, and biting oneself. It will assess the taxonomic specifications of self-injurious behavior (SIB- (e.g., type, frequency, duration)), but also the affective antecedents and consequences as well as the functions of each type of SIB.	Baseline, immediately after treatment, one month after treatment.
THE MODIFIED OVERT AGGRESSION SCALE (MOAS)	Clinician rated scale of aggression. 4 items rated from 0-4. Maximum score is 16 with higher scores indicating higher levels of aggression, used to evaluate and document the "frequency and severity" of aggressive episodes.	Baseline, immediately after treatment, one month after treatment.
Difficulties in Emotion Regulation Scale	Self-report measure of emotion regulation, evaluating individuals' levels of difficulties in regulating emotions. 36-item questionnaires. Each question rated from 1-5. Maximum score is 180 with higher scores indicating greater difficulty in emotion regulation. The instrument presents 36 items on a 5-point Likert scale of frequency (from 1 = almost never, to 5 = almost always).	Baseline, immediately after treatment, one month after treatment.
The Adult Autism Quotient (AQ)	50-item self-report measure of autistic traits. Each of 50 statements are rated from 'definitely disagree' to 'definitely agree'.	Baseline, immediately after treatment, one month after treatment.
Repetitive Behavior Scale-Revised (RBS-R)	43-item clinician rated scale measuring repetitive behaviors associated with ASD. Each item is rated from 0 (behavior does not occur) to 3 (behavior is a severe problem)	Baseline, immediately after treatment, one month after treatment.
Montgomery-Åsberg Depression Rating Scale (MADRS)	10-item clinician rated measure of depressive symptoms. Each item is rated on a scale of 1-6.	Baseline, immediately after treatment, one month after treatment.
Functional connectivity between areas involved in negative emotion regulation	Functional magnetic resonance imaging (fMRI) will be used to measure functional connectivity between areas involved in emotion regulation, previously shown to be involved in irritability. Areas of interest include: ventromedial prefrontal cortex, the amygdala, dorsolateral prefrontal cortex, the striatum.	Baseline, immediately after treatment, one month after treatment.
EEG recordings	Electroencephalography (EEG) will be used to measure brain activity and connectivity before and after treatment. Resting-state EEG (5 minutes) with eyes open and TMS-evoked potential recordings will be taken before and after treatment. We are particularly interested in measuring gamma band activity (>30Hz) in participants while at rest.	Baseline, immediately after treatment, one month after treatment.
Magnetic resonance spectroscopy (MRS)	MRS will be used to measure GABA levels in two brain areas of interest (ventromedial prefrontal cortex and amygdala) before and after treatment.	Baseline, immediately after treatment, one month after treatment.
Aberrant Behavior Checklist-irritability subscale (ABC-I)	A parent/caregiver/clinician completed checklist (58-item) with an irritability subscale (15-item). Each item has a maximum score of 3, meaning that the irritability subscale has a maximum score of 45 and minimum score of 0. Higher scores indicate higher levels of irritability.	Change across time: Baseline minus one month after treatment

Collaborators and Investigators

• Sponsor: Stanford University
• Investigators: Principal Investigator: Lawrence Fung, MD, PhD, Stanford University

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2022
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: September 24, 2019
• First Submitted That Met QC Criteria: March 19, 2020
• First Posted (Actual): March 20, 2020

Study Record Updates

• Last Update Posted (Actual): November 28, 2023
• Last Update Submitted That Met QC Criteria: November 22, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autism Spectrum Disorder
• Other Study ID Numbers: IRB-41458

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