Role of GABAergic Transmission in Auditory Processing in Autism Spectrum Disorder

NCT04798274 | Recruiting

• 2 other identifiers: 20015920-M-0159
• Study Type: interventional
• Target: 106
• Locations: 1 country
• Sites: 1

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

Keywords

GABA; Language; ASD; MEG; MRS

Outcome Measures

Primary Outcomes (4)

• MRS

  GABA+/Cr concentrations in the left pSTC

  immediately pre and post rTMS

• MEG

  Evoked fields and Spectral Power

  immediately pre and post rTMS

• fcMRI

  BOLD correlations across pre-defined ROIs.

  immediately pre and post rTMS

• DTI

  Diffusion tensor derived parameters in the auditory radiations and arcuate fasciculus.

  immediately pre and post rTMS

Secondary Outcomes (2)

• Neuropsychological Assessments

  Baseline

• MEG

  immediately pre and post rTMS

Study Arms (2)

Active cTBS

EXPERIMENTAL

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

Device: Continuous Theta Burst Stimulation

Sham cTBS

SHAM COMPARATOR

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

Device: Continuous Theta Burst Stimulation

Interventions

Continuous Theta Burst Stimulation DEVICE

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.

Active cTBS; Sham cTBS

Eligibility Criteria

• Age: 11 Years - 25 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Pilot Phase
• 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
• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Autism Spectrum Disorder; Language

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders; Communication; Behavior

Study Officials

• Daniel S Pine, M.D.

  National Institute of Mental Health (NIMH)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lindsay M Oberman, Ph.D.

CONTACT

(301) 435-7962; lindsay.oberman@nih.gov

Daniel S Pine, M.D.

CONTACT

(301) 594-1318; daniel.pine@nih.gov

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2021
• First Posted: March 15, 2021
• Study Start: June 15, 2021
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: April 9, 2026

Record last verified: 2026-04-06

Locations

US (1)