Clinical Trials/NCT04798274

NCT04798274

Recruiting

N/A

Role of GABAergic Transmission in Auditory Processing in Autism Spectrum Disorder

National Institute of Mental Health (NIMH)1 site in 1 country106 target enrollmentJune 15, 2021

ConditionsAutism Spectrum Disorder

InterventionsContinuous Theta Burst Stimulation

Overview

Phase: N/A
Intervention: Continuous Theta Burst Stimulation
Conditions: Autism Spectrum Disorder
Sponsor: National Institute of Mental Health (NIMH)
Enrollment: 106
Locations: 1
Primary Endpoint: MRS
Status: Recruiting
Last Updated: 23 days ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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....

Detailed 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, DWI 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 may be scheduled as frequent as about once a week or as far apart as two months per the patient or study team's availability. 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, DWI 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 11-17) with ASD. Exploratory Objective: 3) Characterize the relationship between the neuroimaging and electrophysiological indices obtained in this study and baseline behavioral symptom presentation. Endpoints: Primary Endpoints: 1. MEG: Evoked fields and Spectral Power 2. MRS: GABA+/Cr concentrations in the left pSTC 3. DWI: Diffusion derived parameters in the auditory radiations and arcuate fasciculus. 4. fcMRI: BOLD correlations across pre-defined ROIs. Secondary Endpoints: a. MEG: Inter-trial gamma-band coherence (ITC) and resting state alpha to gamma phase-amplitude coupling. Exploratory Endpoints: a. SRS-2, CELF-5, EVT-3, PPVT-5, ADOS-2 (if available), ADI-R, VABS-III, WASI-II, CBCL, EDI.

Registry

clinicaltrials.gov

Start Date

June 15, 2021

End Date

June 30, 2027

Last Updated

23 days ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

National Institute of Mental Health (NIMH)

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•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

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;