Clinical trial NCT05105126: Non-invasive Brain Stimulation in Children With Autism
Official title: A Pilot Study of Transcranial Direct Current Stimulation (tDCS) in Children With Autism Spectrum Disorder
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Autism Spectrum Disorder
Executive Dysfunction
Child Autism
Keywords: Autism Spectrum Disorder
Transcranial Direct Current Stimulation
Noninvasive Brain Stimulation
Applied Behavior Analysis
Executive Function
Electroencephalogram (EEG)
Lead sponsor: Rutgers, The State University of New Jersey
Sponsor class: OTHER
Collaborators: name: New York State Institute for Basic Research
name: Boston Children's Hospital
First posted: 2021-11-03
Enrollment: 0
Sex: ALL
Minimum age (years): 5
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: The study will use a randomized double-blind controlled placebo (sham vs. active tDCS) crossover design. The study will involve 5 total months of participation. Participants will be randomized into one of the two groups:

Group A) 20 active tDCS stimulation followed by 20 sham stimulation; or

Group B) 20 sham stimulation followed by 20 active tDCS stimulation
Primary purpose: TREATMENT

Brief summary: Although many children diagnosed with autism spectrum disorder (ASD) make significant progress in learning and their cognitive skills improve with applied behavior analysis (ABA), there are a significant number of children who show an absence or a plateau in various skills. Deficits in executive functioning are likely to be involved in many of these cognitive and learning disabilities due to poor functioning of the prefrontal cortex. Currently, the use of biological methods for improving learning and cognition is largely unexplored in research and practice.

The aim of this study is to use of transcranial direct current stimulation (tDCS) in combination with ABA to improve the acquisition of educational programs for students with ASD. tDCS is a low-level electrical neurostimulation and is most effective when used in combination with an active training or teaching, facilitating the neuronal circuits used for that task.

tDCS has been used for various indications over a couple of decades and has been shown to be very safe and has been well-tolerated by children with ASD. The mechanism of tDCS is not clear, however animal studies show that tDCS can stimulate the flow of calcium ions through channels in the astrocytes, activating them, and facilitating their role in synapse formation and therefore learning.

Detailed description: Children with ASD experience a wide range of outcomes, and not all children respond effectively to behavioral interventions. This study uses a novel biologic intervention that combines electrical brain stimulation with ABA treatment to target some of the cognitive deficits in ASD that until now have been relatively refractory to treatment.

There is accumulating evidence of tDCS being effective in treating the comorbidities as well as the core symptoms of ASD. tDCS is most effective when used simultaneously with an active intervention. In this study, the effects of tDCS alone and in combination with ABA on the executive functioning skills and the core symptoms of ASD will be examined and monitored using an objective neurophysiological test (EEG).

This is a double-blind, sham-controlled crossover study involving 20 participants. tDCS will be administered while ABA therapy is being implemented. Programs aimed at language and other cognitive functions will be emphasized. tDCS will be applied bi-frontally with the anode at F3 and the cathode at F4. Forty stimulation sessions will be done (20 active, 20 sham) lasting 20 minutes per session, at 1 milliampere.

Eligibility criteria: Inclusion Criteria:

1. Males and females between 5 and 12 years with autism
2. Enrolled in an ABA program (school or in-home) supervised by a Board Certified Behavior Analyst (BCBA)
3. Stable medical and behavioral treatments for at least 4 weeks prior to, and during the study
4. Able to tolerate wearing tDCS as determined during a week-long daily desensitization training.

Exclusion Criteria:

1. Any implanted metal device (heart pacemaker, cochlear implant, surgical clips, etc.)
2. Severe neurological disorders such as TBI, brain tumor, intracranial infection
3. Seizure disorder with a seizure within the last two years
4. Skull defect
5. Peripheral blindness or deafness
6. Medication that might affect tDCS: There have been a few studies concerning the effect of various medications on tDCS. Some may block and others may enhance the effects depending on many factors. The assay used to test these medications was its effect on the motor cortex after stimulation and this may not apply to our montages, however, in order to minimize the chances of having medication affect our results, participants taking the following medications will be excluded:

   1. Na or Ca channel blockers which will include all anti-seizure medications
   2. Medications that affect the NMDA receptors including dextromethorphan, cycloserine
   3. Serotonin reuptake inhibitors
   4. Dopamine stimulating or blocking medications including pergolide, bromocriptine and all antipsychotic medications
   5. Norepinephrine stimulating or blocking agents including propranolol and the stimulants
   6. Drugs that can lower seizure threshold \[imipramine, amitriptyline, doxepin, nortriptyline, maprotiline, chlorpromazine, clozapine, foscarnet, ganciclovir, ritonavir, amphetamines, phencyclidine, ketamine, gamma-hydroxybutyrate (GHB), alcohol, theophylline\]
   7. Barbiturates, benzodiazepines, meprobamate, chloral hydrate in the past 4 weeks
7. Acute skin disease
8. History of magnetic or electrical stimulation

Primary outcomes:
measure: Change in the Behavior Rating Inventory of Executive Function (BRIEF)
timeFrame: Change measured once per month (at the end of each phase) for 5 months
measure: Change in Electrodncephalogram (EEG)
timeFrame: Change measured once per month (at the end of each phase) for 5 months
Secondary outcomes:
measure: Change in the Pervasive Developmental Disorder Behavior Inventory (PDDBI)
timeFrame: Change measured once per month (at the end of each phase) for 5 months
measure: Change in discrete trial training (DTT) data from applied behavior analysis (ABA) therapy
timeFrame: Obtained once at the completion of the study (5 months after the start of the study)
Other outcomes:
measure: Vineland Adaptive Behavior Scales (for demographic purposes)
timeFrame: Once during 4-week baseline for the entire study
measure: Leiter-3 nonverbal intelligence assessment (for demographic purposes)
timeFrame: Once during 4-week baseline (if a similar test was not done in the past three years) for the entire study
Locations:
city: New Brunswick
country: United States
facility: Department of Pediatrics, Division of Pediatric Neurology, Robert Wood Johnson Medical School
state: New Jersey
Study officials:
affiliation: Department of Pediatrics, Division of Pediatric Neurology Robert Wood Johnson Medical School (RWJMS)
name: Barbie Zimmerman-Bier, M.D.
role: PRINCIPAL_INVESTIGATOR
References: