Recruiting

GABAergic Transmission

Sponsor:

National Institute of Mental Health (NIMH)

Code:

NCT04798274

Conditions

Autism Spectrum Disorder

Eligibility Criteria

Sex: All

Age: 11 - 25

Healthy Volunteers: Accepted

Interventions

Continuous Theta Burst Stimulation

Study Details

Brief summary:

Background:

Autism spectrum disorder (ASD) is a complex neurodevelopmental syndrome. Researchers think brain development may be controlled by gamma-aminobutyric acid (GABA). They want to learn how abnormalities in the GABA system may contribute to ASD.

Objective:

To see if repetitive transcranial magnetic stimulation (rTMS) creates short-term changes in how different parts of the brain communicate.

Eligibility:

Right-handed people ages 11-17 with ASD, and healthy volunteers ages 18-25.

Design:

Participants will be screened with:

Medical history

Physical exam

Medicine review

Neurological exam

Psychological tests and rating scales

Forms and surveys.

Participants will have a hearing test and ear exam.

Participants will have magnetic resonance imaging (MRI) of the brain. They will lie on a table that moves in and out of the MRI scanner. They may look at a screen while in the scanner. A coil will be placed over their head.

Participants will have magnetic resonance spectroscopy. It takes pictures of chemicals in the brain using the MRI scanner.

Participants will have magnetoencephalography. They will sit in a chair. A helmet with magnetic field sensors will be placed on their head.

Participants will have TMS. A wire coil will be held on their scalp. A brief electrical current will pass through the coil.

Participants will have electromyography. Sticky pad electrodes will be placed on the skin during TMS. The electrical activity of their muscles will be measured.

Participants will have rTMS. It uses short bursts of magnetic pulses to affect brain activity.

ASD participants may have visits scheduled as often as 1 time a week or as far apart as 2 months based on the participants or study team's availability. Healthy volunteers will have 3 visits over 3-4 weeks....

Conditions

Autism Spectrum Disorder

Study ID

NCT04798274

Start date

Jun 15, 2021

Status verified date

Apr 6, 2026

Completion date

Jun 30, 2027

Anticipated

Primary completion date

Jun 30, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 11 - 25

Healthy Volunteers: Accepted

  • INCLUSION CRITERIA:

Pilot Phase

Inclusion criteria

  • Ability to provide informed consent
  • Age: 18-25 years
  • Must meet the definition of "Healthy Control" having completed the screening assessment under protocol 01-M-0254, "The Evaluation of Patients with Mood and Anxiety Disorders and Healthy Volunteers" or under protocol 17-M-0181, "Recruitment and Characterization of Research Volunteers for NIMH Intramural Studies".

Main Study Phase

Inclusion criteria

  • Ability to provide informed assent and parent consent (Parents of children enrolling on the study do not need to be able to speak English. A consent form is available in English or Spanish for parents of children who enroll.)
  • Age: 11-17 years
  • Community Diagnosis of ASD based on DSM-IV or DSM-5 criteria (reviewed by a member of the Neurodevelopmental and Behavioral Phenotyping Service)
  • Wechsler Abbreviated Scale of Intelligence, Second Edition (WASI-II). WASI-II will be used as a measure of intellectual function. Children will be included when FSIQ > 70.
  • Right-handed: to reduce heterogeneity.
  • Hearing: Normal hearing in order to complete the behavioural assessments.

EXCLUSION CRITERIA:

Participants will be screened to exclude individuals with co-occurring neurological or medical conditions that might confound the results, as well as to exclude subjects in whom MRI or rTMS might result in increased risk of side effects or complications. This accounts for the majority of the exclusion criteria listed:

Exclusion criteria

Participants will be screened to exclude individuals with neurological, psychological/behavioral or medical conditions, as well as to exclude subjects in whom MRI or rTMS might result in increased risk of side effects or complications. This accounts for the majority of the exclusion criteria listed:

Pilot Phase

  • Non-English Speakers
  • Known Neurological Disorder
  • Known Psychiatric Disorder
  • Known genetic disorder (e.g., NF1, tuberous sclerosis), acquired neurologic disease (e.g. stroke, tumour), cerebral palsy, intracranial pathology or significant dysmorphology;
  • History of fainting spells of unknown or undetermined etiology that might constitute seizures;
  • History of seizures, diagnosis of epilepsy, or immediate (1st degree relative) family history epilepsy;
  • Chronic (particularly) uncontrolled medical conditions that may cause a medical emergency in case of a provoked seizure (cardiac malformation, cardiac dysrhythmia, asthma, etc.);
  • Past or Current History of Tinnitus
  • Any implant, prosthesis or other permanent alteration of the body that, in the opinion of the investigator, would be unsafe with MRI or TMS or that would produce an artifact that would compromise the integrity of data;
  • Signs of increased intracranial pressure;
  • Intracranial lesion (including incidental finding on MRI) that, in the opinion of the investigator, would be unsafe with MRI or TMS or that would produce an artifact that would compromise the integrity of data;
  • History of any head trauma within 6 months of screening, or beyond 6 months prior to screening, history of head trauma with evidence of traumatic abnormality appearing on a brain scan, or with loss of consciousness >5 minutes, or with other sequelae, excluding headache, lasting > 24 hours.
  • Pregnancy;
  • Participants who have received rTMS less than 7 days prior to enrollment;
  • Individuals currently taking GABAergic medications or any other medication that, in the opinion of the investigator, significantly lowers seizure threshold;
  • Individuals for whom it is not safe or appropriate to remain on a stable pharmacotherapy (for nonexclusionary medications) for six weeks prior to and over the course of their participation in the study;
  • A current NIMH employee or staff or their immediate family member.

Main Study Phase

  • Non-English Speakers
  • Known genetic disorder that is either associated with the ASD diagnosis or that in the opinion of the investigator may increase the risk to the participant or compromise the integrity of the data;
  • Acquired neurologic disease (e.g. stroke, tumour), cerebral palsy, intracranial pathology or significant dysmorphology;
  • History of fainting spells of unknown or undetermined etiology that might constitute seizures;
  • History of seizures, diagnosis of epilepsy, or immediate (1st degree relative) family history epilepsy;
  • Any progressive (e.g., neurodegenerative) neurological disorder;
  • Chronic (particularly) uncontrolled medical conditions that may cause a medical emergency in case of a provoked seizure (cardiac malformation, cardiac dysrhythmia, asthma, etc.);
  • Past or Current history of clinically significant tinnitus as determined by an audiologist or other-licensed clinician.
  • Any implant, prosthesis or other permanent alteration of the body that, in the opinion of the investigator, would be unsafe with MRI or TMS or that would produce an artifact that would compromise the integrity of data;
  • Signs of increased intracranial pressure;
  • Intracranial lesion (including incidental finding on MRI) that, in the opinion of the investigator, would be unsafe with MRI or TMS or that would produce an artifact that would compromise the integrity of data;
  • History of any head trauma within 6 months of screening, or beyond 6 months prior to screening, history of head trauma with evidence of traumatic abnormality appearing on a brain scan, or with loss of consciousness >5 minutes, or with other sequelae, excluding headache, lasting > 24 hours.
  • Pregnancy;
  • Participants who have received prior rTMS;
  • Active or History of psychosis, bipolar disorder, active severe substance use disorders (within the last month), have active suicidal intent or plan as detected on screening instruments or in the investigator team's opinion is likely to attempt suicide within 6 months;
  • Individuals currently taking GABAergic medications or any other medication or medication change that, in the opinion of the investigator, significantly lowers seizure threshold;
  • Past or present medical or neurological condition, disease, disorder, genetic finding, or injury that, in the opinion of the Investigator, may significantly increase the potential risks of study participation, reduce or compromise a subject's ability to fully comply with all study requirements for the duration of the study or may compromise the integrity of the data.

Study Design

Enrollment

106 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

experimental: Active cTBS

This intervention involves active repetitive magnetic stimulation. The coil emits a magnetic field

sham comparator: Sham cTBS

This intervention involves sham (placebo) repetitive transcranial magnetic stimulation. The coil is blinded, but does not emit any magnetic field

Interventions

Continuous Theta Burst Stimulation

Continuous theta burst stimulation (cTBS) will be applied using a MagPro X100 (MagVenture, Inc. Alpharetta, GA). The cTBS protocol consists of bursts of three pulses of 50 Hz stimulation repeated at 200 ms intervals (5 times per second) for 40 seconds (for a total of 600 pulses). Stimulation will be applied at an intensity of 80% of active motor threshold (AMT). Brainsight (Rogue Research) frameless neuronavigation system will be used to target the specific structural MRI-defined region of stimulation.

Primary outcome measure

  • MRS [ Time Frame: immediately pre and post rTMS ]
  • MEG [ Time Frame: immediately pre and post rTMS ]
  • fcMRI [ Time Frame: immediately pre and post rTMS ]
  • DTI [ Time Frame: immediately pre and post rTMS ]

Central Contacts and Locations

Central contacts

Locations

National Institutes of Health Clinical Center

Recruiting

Bethesda, Maryland, United States, 20892

Contacts

For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)

800-411-1222prpl@cc.nih.gov

More Information

Sponsor

National Institute of Mental Health (NIMH)

Last update posted

Apr 9, 2026

Last verified

Apr 6, 2026

Keywords

  • GABA
  • Language
  • ASD
  • MEG
  • MRS

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by National Institute of Mental Health (NIMH) on 2026-04-09.