Transcranial Magnetic Stimulation (TMS) to Treat Depression in Autism Spectrum Disorder

NCT06142955 | Recruiting FDA Device

• 2 other identifiers: 2000035486000
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This study will assess clinical and behavioral measures along with electroencephalogram (EEG), event-related potentials (ERPS), and eye-tracking (ET) prior to and following a single intermittent Theta Burst Stimulation (iTBS) session to provide preliminary insight into the potential of TMS as an intervention for depression in individuals with Autism Spectrum Disorder (ASD).

Conditions

Autism Spectrum Disorder

Outcome Measures

Primary Outcomes (3)

• Change in Electroencephalogram (EEG) brain responses to sad faces

  As measured by amplitude and latency of event related potentials (ERP) (the right lateralized P100, P200 and amplitude of N170) to sad faces. EEG: an electrophysiological assay that measures brain activity from the scalp.

  baseline and up to week 2

• Change in eye tracking (ET) to sad faces

  ET will measure participant attention to the screen and be used to ensure that participants are looking at the stimulus display screen during the course of the experimental paradigms. Change in Proportion of fixation (POF) to the eye region in sad faces as measured by ET.

  baseline and up to week 2

• Change in Auditory Steady State Response (ASSR)

  ASSR measures an electrophysiological response in the human cortex after presenting stimulation consisting of pure tones at certain frequencies. For assessment of ASSRs, subjects will sit in an acoustically shielded booth in front of a computer monitor with eyes open, while passively listening to click trains presented through Etymotic insert ER-1 earphones (Etymotic Research, Elk Grove Village, IL). Stimuli will consist of standard, unattended (nontarget) auditory click trains from a three-stimulus oddball tasks. The output is thus measured in the EEG recording which is analyzed in the frequency domain. Measures of inter-trial coherence (ITC) are used to determine neural synchrony through the ASSR task, by quantifying the degree of phase consistency across trials. ASSR Power is the magnitude of the brain's voltage response to a stimulus and the consistency across trials of the time course of this time-locked response.

  baseline and up to week 2

Secondary Outcomes (4)

• Change in neural processing on EEG to sad faces

  baseline and up to week 2

• Change in ET to different emotionally valenced faces

  baseline and up to week 2

• Change in ET to neutral faces and non-social stimuli

  baseline and up to week 2

• Change in Frith Happé Animations Task

  baseline and up to week 2

Study Arms (8)

ASD with depression, iTBS then Sham

EXPERIMENTAL

Participants having ASD with depression will undergo EEG and ET with TMS prior to and following a single iTBS session. Participants first received iTBS then sham approximately one week apart.

Device: MAGSTIM Rapid2 TMS system

ASD with depression, Sham then iTBS

EXPERIMENTAL

Participants having ASD with depression will undergo EEG and ET with TMS prior to and following a single iTBS session.Participants first received sham then iTBS approximately one week apart.

Device: MAGSTIM Rapid2 TMS system

ASD without depression, iTBS then Sham

EXPERIMENTAL

Participants having ASD without depression will undergo EEG and ET with TMS prior to and following a single iTBS session. Participants first received iTBS then sham approximately one week apart.

Device: MAGSTIM Rapid2 TMS system

ASD without depression, Sham then iTBS

EXPERIMENTAL

Participants having ASD without depression will undergo EEG and ET with TMS prior to and following a single iTBS session.Participants first received sham then iTBS approximately one week apart.

Device: MAGSTIM Rapid2 TMS system

TD with depression, iTBS then Sham

EXPERIMENTAL

Participants that are TD with depression will undergo EEG and ET with TMS prior to and following a single iTBS session. Participants first received iTBS then sham approximately one week apart.

Device: MAGSTIM Rapid2 TMS system

TD with depression, Sham then iTBS

EXPERIMENTAL

Participants that are TD with depression will undergo EEG and ET with TMS prior to and following a single iTBS session. Participants first received sham then iTBS approximately one week apart.

Device: MAGSTIM Rapid2 TMS system

TD without depression, iTBS then Sham

EXPERIMENTAL

Participants that are TD without depression will undergo EEG and ET with TMS prior to and following a single iTBS session. Participants first received iTBS then sham approximately one week apart.

Device: MAGSTIM Rapid2 TMS system

TD without depression, Sham then iTBS

EXPERIMENTAL

Participants that are TD without depression will undergo EEG and ET with TMS prior to and following a single iTBS session. Participants first received sham then iTBS approximately one week apart.

Device: MAGSTIM Rapid2 TMS system

Interventions

MAGSTIM Rapid2 TMS system DEVICE

The device will administer TMS pulses in bursts at fixed intervals for a total of 600 pulses over 190 seconds after first assessing the participants motor threshold (MT). During the sham stimulation condition, the TMS coil will be tilted 90° tangential to the scalp during the administration so that the orientation is not biologically active and will not elicit a muscle contraction. This sham condition will look and sound just like real TMS.

ASD with depression, Sham then iTBS; ASD with depression, iTBS then Sham; ASD without depression, Sham then iTBS; ASD without depression, iTBS then Sham; TD with depression, Sham then iTBS; TD with depression, iTBS then Sham; TD without depression, Sham then iTBS; TD without depression, iTBS then Sham

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Individuals from Yale University and the surrounding community who are between the ages of 18 and 40 years old with or without a diagnosis of depression. Or individuals between the ages of 18 and 40 years old with a diagnosis of autism spectrum disorder, autistic disorder, PDD NOS, or Asperger syndrome with or without a diagnosis of depression.
• A depression score on the HDRS-17 of at least 20 will be used as a cut-off for depression.
• Participants are unmedicated or on stable medication treatment for at least two weeks.
• Willingness and ability to participate in an EEG and eye-tracking procedure.
• Provision of signed and dated informed consent.

You may not qualify if:

• Participants reporting significant head trauma or serious brain illness.
• Participants unable to provide signed informed consent.
• Participants with major psychiatric illness that would preclude completion of study measures. Participants with diagnosis of a psychotic or bipolar illness with be excluded.
• Participants with a history of serious medical illness, stroke, seizures, epileptiform EEG abnormalities, or family history of epilepsy.
• Participants taking prescription medications that may affect cognitive processes under study.
• Participants taking any medication that may increase their risk of seizures.
• Participants who have taken alcohol or recreational drugs within the preceding 24 hours prior to the scheduled study visit as determined by the urine toxicology test.
• Participants with a history of substance or alcohol abuse or dependence in the past 6 months.
• Participants with a significant risk of suicide or a h/o suicide attempt in the last 6 months. Participants with active suicidal ideation will be excluded from the study.
• Females of known/suspected pregnancy or who test positive on a pregnancy test.
• Participants with a history of metalworking or injury by shrapnel or metallic objects.
• Participants with a history of prior TMS therapy or use of an investigational drug within 12 weeks of visit
• Participants with an IQ below 80 (as confirmed by the WASI, Wechsler Abbreviated Scale of Intelligence)

Sponsors & Collaborators

• Yale University: lead
• American Academy of Child Adolescent Psychiatry.: collaborator

Study Sites (1)

Yale Psychiatric Hospital

New Haven, Connecticut, 06520, United States

RECRUITING

MeSH Terms

Conditions

Autism Spectrum Disorder

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Study Officials

• Sherab Tsheringla, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sherab Tsheringla, MD

CONTACT

2032158046; sherab.tsheringla@yale.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Typically developing (TD) controls and ASD participants with and without depression will receive both active and sham TMS in a randomized crossover assignment involving two study sessions.

Study Record Dates

• First Submitted: November 15, 2023
• First Posted: November 22, 2023
• Study Start: April 30, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: July 2, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)