Clinical trial NCT04446442: Cerebellar tDCS in Children With Autism Spectrum Disorder
Official title: Biologic Effects and Efficacy of Cerebellar tDCS in Children With Autism Spectrum Disorder
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Autism Spectrum Disorder
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
First posted: 2020-06-25
Enrollment: 60
Sex: ALL
Minimum age (years): 4
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The purpose of this research study is to investigate whether tDCS to the cerebellum (specifically, the right crus I/II area of the cerebellum) of children and young adults with autism spectrum disorders (ASD) is safe and to examine its effects on some of the symptoms of ASD, such as repetitive behaviors and hyperactivity.

Detailed description: The study will be randomized, double-blind, and controlled. It will involve a group of 60 children with ASD (diagnosed with the Autism Diagnostic Observation Schedule (ADOS-2) by a research-reliable clinician) coming in for an orientation day, where participants will be acclimated to the testing environment, as well as undergo safety screening, and a mock MRI. The investigators will recruit from a sample of children diagnosed with ASD (The diagnosis must be made by experienced, research reliable clinicians using gold standard measures including the Autism Diagnostic Observation schedule Second Edition Study, or ADOS-2 and a diagnostic and developmental parent interview). The investigators will request this information from the institution where the diagnosis was given with parent/caregiver permission. Diagnostic information will be reviewed by the study neuropsychologist, and if additional testing is needed to update or confirm the diagnosis, the investigators will administer an ADOS-2 here at UTSW prior to other baseline measures. If diagnostic information from a previous CADD clinic visit or an outside institution by a research reliable clinician is current, the investigators will accept it.

Participants will complete in a variety of tasks during a pre-treatment visit. In addition, baseline behavioral measurements will be performed. These tests include an abbreviated measure of cognitive ability using the Stanford Binet-Fifth Edition, interpretation of facial expressions, memory for faces, reading the mind in the eyes, triangle animations, cyberball /social ball throwing, dimensional card change sort, and caregiver-completed behavioral scale including the Autsim Spectrum Rating Scale (ASRS). Participants will also be asked about their mood before, during, and after treatment. Participants will then be randomly assigned into either a sham treatment group or an active treatment group. The next time the participants come in, participants vitals will be monitored in addition to eye monitoring and will undergo either 1 mA for 20 minutes of anodal or cathodal tDCS administration to Right Crus I/II area of the cerebellum or sham treatment. Participants will undergo fMRI imaging prior, during, and after anodal or cathodal tDCS. After the scans, testing will be repeated and include interpretation of facial expression, memory for faces, reading the mind in the eyes, triangle animations, theory of mind, cyberball/social ball throwing, and dimensional card change sort. At the end of the visit parents/guardians/participants will receive a safety questionnaire asking about the presence and severity of the possible side effects. The participants will then follow up in 1 week with the safety questionnaire and at 1 month with the safety questionnaire and the Autism Spectrum Rating Scale.

Study Procedures:

Investigators, including those involved in questionnaire and behavioral scales administration and fMRI scanning/interpreting will be blinded to which treatment group participants are in. Staff members in charge of applying tDCS will be aware of what treatment group the participant is in but will not be involved in analysis of data to ensure blinding of results. As far as the tDCS procedure goes, the device consists of a programmable current source with a rechargeable battery with two wires connected to electrodes in fabric pads. The device cannot be plugged into an outlet while the electrodes are connected, ensuring safety. tDCS pads are moistened with 0.9% normal saline and placed on the participant's scalp using elastic bands. During stimulation, the electrodes will apply 1 mA of constant DC electrical current. Current will be increased over 10-60 seconds. The current will be applied for no more than 20 minutes, after which the current is decreased over 10-60 seconds. In sham tDCS, the current is increased and then immediately decreased to provide sensations associated with tDCS (mild tingling or itching, which blinds the participant).

Testing will take place before (on orientation day) and after tDCS. Baseline testing includes an ADOS-2 if deemed necessary, an abbreviated cognitive measure, interpretation of facial expressions, memory for faces, reading the mind in the eyes, triangle animations, cyberball /social ball throwing, dimensional card change sort, and caregiver-completed behavioral scale including the Autsim Spectrum Rating Scale.. Testing immediately after tDCS includes only the following: interpretation of facial expressions, memory for faces, reading the mind in the eyes, triangle animations, theory of mind, cyberball/social ball throwing, and dimensional card change sort.

Participants with ASD will come in on designated orientation days and be assigned an alphanumeric identifier to ensure confidentiality. An initial safety screening will be done to ensure no exclusion criteria are met. Participants will then be randomly split into either a sham group or a treatment group. Baseline testing will be completed. Participants will then be allowed to explore and become acclimated with study equipment, and a mock MRI will be done on the first visit at the UTSW Advanced Imaging Research Center (AIRC).

Participants will be desensitized to the sounds and tactile sensations of the fMRI environment while in a space similar to that of the scanner bore. Participants will practice remaining still within the mock MRI while viewing a movie, and biofeedback is used to train participants to keep their movement \<1mm during practice periods of 10 minutes. Participants should be able to complete all of the screening in one visit. If participants cannot due to time constraints participants will be brought back in on a different day to complete the screening visit.

The next time participants return, participants will be hooked up to vitals and eye movement monitoring and will be placed in the fMRI machine so the "before" scanning can begin. After this "before" scan, tDCS electrodes will be applied and participants will again be placed in the fMRI machine for the "during" scan. As soon as scanning begins, tDCS (either sham or treatment of 1 mA for 20 minutes of anodal tDCS administration to the Right Crus I/II area of the cerebellum) will begin as well. During tDCS treatment caregivers will receive a safety questionnaire for them to assess any side effects occurring in their child. After this scan, the tDCS electrode will be removed, and a final "after" fMRI scan will take place. The safety questionnaire will be given after tDCS at the end of the visit and behavioral tests are complete.The time estimated for all of this is about 90-180 minutes.

The Safety Questionnaire will be assessed again with follow-up visits 1 week and 1 month afterwards using the same caregiver-completed scales.

Eligibility criteria: Inclusion Criteria:

* 4-17 years old
* Diagnosed with ASD and ADOS-2
* IQ Score no less than 70 (1.5 Standard Deviations below the mean)
* Language Level (Speech consists of, at minimum, flexible, spontaneous, simple, sentences)

Exclusion Criteria:

* Brain implants, metal implants, pacemakers, or biomedical devices
* Diagnosis of epilepsy
* Hearing or visual impairments
* History of brain injury
* Known brain abnormalities not associated with ASD

Primary outcomes:
measure: Incidence of tDCS associated side effects assessed by tDCS Safety Assessment
timeFrame: Post-Intervention up to one month
Secondary outcomes:
measure: Change in Autism Spectrum Disorder Symptoms assessed by NEPSY-2 Subtests
timeFrame: Pre-Intervention at 1 week and Post-Intervention at 1 hour
measure: Change in Autism Spectrum Disorder Symptoms assessed by Reading the Mind in the Eyes
timeFrame: Pre-Intervention at 1 week and Post-Intervention at 1 hour
measure: Change in Autism Spectrum Disorder Symptoms assessed by Triangle Animations/Social Perception Task
timeFrame: Pre-Intervention at 1 week and Post-Intervention at 1 hour
measure: Change in Autism Spectrum Disorder Symptoms assessed by Cyberball/Social Ball Throwing Task
timeFrame: Pre-Intervention at 1 week and Post-Intervention at 1 hour
measure: Change in Autism Spectrum Disorder Symptoms assessed by Dimensional Change Card Sort
timeFrame: Pre-Intervention at 1 week and Post-Intervention at 1 hour
measure: Change in Autism Spectrum Disorder Symptoms assessed by Autism Spectrum Rating Scale
timeFrame: Pre-Intervention at 1 week and Post-Intervention at 1 week and 1 month
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Children's Medical Center
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern
state: Texas
Study officials:
affiliation: University of Texas Southwestern Medical Center
name: Peter Tsai, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: