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

Back to results

Primary Purpose

Status

Not yet recruiting

Phase

Not Applicable

Locations

Study Type

Interventional

Intervention

Intermittent theta-burst stimulation (iTBS)

About this trial

This is an interventional treatment trial for Autism Spectrum Disorder

Eligibility Criteria

22 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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)
Age 22 to 55.
Adults who are physically healthy.
No significant current psychosocial stressors per history.
Full scale IQ > 50.
ABC-I score of 18 or greater.
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.

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Active intermittent theta-burst stimulation (iTBS)

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

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.

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).

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'.

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)

Montgomery-Åsberg Depression Rating Scale (MADRS)

10-item clinician rated measure of depressive symptoms. Each item is rated on a scale of 1-6.

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.

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.

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.

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.

Full Information

NCT ID

NCT04316338

First Posted

September 24, 2019

Last Updated

May 6, 2021

Sponsor

Stanford University

1. Study Identification

Unique Protocol Identification Number

NCT04316338

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2021

Overall Recruitment Status

Not yet recruiting

Study Start Date

May 1, 2022 (Anticipated)

Primary Completion Date

May 1, 2024 (Anticipated)

Study Completion Date

May 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Stanford University

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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Autism Spectrum Disorder

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Model Description

Open-label design.

Masking

None (Open Label)

Allocation

N/A

Enrollment

10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Active intermittent theta-burst stimulation (iTBS)

Arm Type

Experimental

Arm Description

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.

Intervention Type

Device

Intervention Name(s)

Intermittent theta-burst stimulation (iTBS)

Intervention Description

Non-invasive brain stimulation technique

Primary Outcome Measure Information:

Title

Aberrant Behavior Checklist-irritability subscale (ABC-I)

Description

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.

Time Frame

Change across time: Baseline minus immediately after final treatment

Secondary Outcome Measure Information:

Title

Irritability Questionnaire

Description

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.

Time Frame

Baseline, every week of treatment (1-6), immediately after treatment, one month after treatment.

Title

Self-injury questionnaire (SIQ)

Description

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.

Time Frame