Role of GABAergic Transmission in Auditory Processing in Autism Spectrum Disorder

  • STATUS
    Recruiting
  • End date
    Jun 30, 2025
  • participants needed
    106
  • sponsor
    National Institute of Mental Health (NIMH)
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Updated on 13 August 2023
See if I qualify
Accepts healthy volunteers

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 14-17 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 will have 7 visits over 2-3 months. Healthy volunteers will have 3 visits over 3-4 weeks....

Description

Study Description:

This will be a within-subject, controlled, proof-of-mechanism study.

Objectives

The study aims to evaluate the relationship between local GABA concentration, structural and functional network connectivity and MEG measures of auditory and language processing in adolescents with ASD and the acute impact of a single session of continuous theta burst stimulation over left posterior superior temporal cortex (pSTC) on these measures. We hypothesize that GABA concentrations, DTI measures of tissue microstructure and fcMRI obtained BOLD correlations within the language network will significantly contribute to the prediction model for MEG indices of auditory and language processing. Participation in the study involves about seven study visits. Some of the visits may be split up to shorten the length of session and limit fatigue. Visits will be scheduled about once a week. All visits must be completed within six months of the date of enrollment.

Primary Objective: The overall goal of the current study is to 1) Characterize the relationship between an individual's baseline local cortical GABA concentration, DTI measures of auditory and language network tissue microstructure, and fcMRI indices of local and long-range network functional connectivity (predictor variables) and MEG indices of auditory and language processing (dependent variables).

Secondary Objectives: 2) Evaluate the impact of a single session of cTBS over the left pSTC on these MRS and MEG indices in adolescents (age 14-17) with ASD.

Endpoints

Primary Endpoints:

  1. MEG: Evoked fields and Spectral Power
  2. MRS: GABA+/Cr concentrations in the left pSTC
  3. DTI: Diffusion tensor derived parameters in the auditory radiations and arcuate fasciculus.
  4. fcMRI: BOLD correlations across pre-defined ROIs.

Secondary Endpoints:

  1. MEG: Inter-trial gamma-band coherence (ITC) and resting state alpha to gamma phase-amplitude coupling.
  2. SRS-2, CELF-5, EVT-3, PPVT, ADOS-2 (if available), ADI-R, VABS-III, WASI- II.

Details
Condition Autism Spectrum Disorder
Treatment transcranial magnetic stimulation, continuous theta burst stimulation
Clinical Study IdentifierNCT04798274
SponsorNational Institute of Mental Health (NIMH)
Last Modified on13 August 2023

Eligibility

 Yes No Not Sure

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
Age: 14-17 years
Community Diagnosis of ASD based on DSM-IV or DSM-5 criteria
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 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 genetic disorder (e.g., NF1, tuberous sclerosis), acquired neurologic disease
Known Psychiatric Disorder
(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
Past or Current History of Tinnitus
history epilepsy
Any implant, prosthesis or other permanent alteration of the body that, in the opinion
Chronic (particularly) uncontrolled medical conditions that may cause a medical
of the investigator, would be unsafe with MRI or TMS or that would produce an artifact
emergency in case of a provoked seizure (cardiac malformation, cardiac dysrhythmia
that would compromise the integrity of data
asthma, etc.)
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
Signs of increased intracranial pressure
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
Pregnancy
Participants who have received rTMS less than 7 days prior to enrollment
Individuals currently taking GABAergic medications or any other medication that, in
A current NIMH employee or staff or their immediate family member
the opinion of the investigator, significantly lowers seizure threshold
Main Study Phase
Non-English Speakers
excluding headache, lasting > 24 hours
Any progressive (e.g., neurodegenerative) neurological disorder
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
Signs of increased intracranial pressure
Known genetic disorder (e.g., NF1, tuberous sclerosis), acquired neurologic disease
(e.g. stroke, tumour), cerebral palsy, intracranial pathology or significant
Pregnancy
dysmorphology
Past or Current History of Tinnitus
Participants who have received prior rTMS
History of fainting spells of unknown or undetermined etiology that might constitute
Any implant, prosthesis or other permanent alteration of the body that, in the opinion
seizures
of the investigator, would be unsafe with MRI or TMS or that would produce an artifact
History of seizures, diagnosis of epilepsy, or immediate (1st degree relative) family
that would compromise the integrity of data
history epilepsy
A current NIMH employee or staff or their immediate family member
Intracranial lesion (including incidental finding on MRI) that, in the opinion of the
Chronic (particularly) uncontrolled medical conditions that may cause a medical
investigator, would be unsafe with MRI or TMS or that would produce an artifact that
emergency in case of a provoked seizure (cardiac malformation, cardiac dysrhythmia
would compromise the integrity of data
asthma, etc.)
<TAB>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
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 that, in
the opinion of the investigator, significantly lowers seizure threshold
excluding headache, lasting > 24 hours
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
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