Evaluating the Efficacy of Repetitive Transcranial Magnetic Stimulation Combined With Auditory Integration Training for Children With Autism Spectrum Disorder: Protocol for a Randomized Sham-Controlled Trial.

Background: Autism spectrum disorder (ASD) represents a significant public health challenge characterized by persistent social communication deficits and restricted, repetitive patterns of behavior. Current interventions show limited efficacy, particularly for core symptoms. Repetitive transcranial magnetic stimulation (rTMS) and auditory integration training (AIT) have independently demonstrated promise in addressing neurophysiological abnormalities associated with ASD. Objective: This study aims to evaluate the clinical efficacy of a combined rTMS and AIT intervention compared to rTMS alone and sham stimulation in children with ASD. Methods: This is a randomized, sham-controlled trial that will recruit 80 children aged 2 to 6 years with a confirmed ASD diagnosis. The randomization of the first 8 participants in this study used a 1:1:1 ratio. To more effectively test the core hypothesis (ie, the efficacy of the combined intervention), greater statistical power will be concentrated on the intervention group (rTMS+AIT), and the randomization ratio was ultimately adjusted to 2:1:1-specifically, (1) rTMS combined with AIT (n=40), (2) rTMS alone (n=20), or (3) sham rTMS (n=20). Primary outcome measures include the Autism Behavior Checklist and Childhood Autism Rating Scale. Secondary outcomes are the Strengths and Difficulties Questionnaire and Repetitive Behavior Scale-Revised. Assessments will be conducted at baseline, an interim time point, and immediately after the intervention. Data will be analyzed using SPSS (version 25.0; IBM Corp). Results: This study has received funding, with data collection commencing in April 2024. Due to the small initial sample size of 8 participants (5 male and 3 female), no formal statistical comparisons of baseline characteristics between groups have been conducted at this time. It is anticipated that the rTMS combined with AIT intervention will exhibit superior efficacy compared to rTMS only. Conclusions: This will be the first sham-controlled trial to systematically investigate the potential synergistic effects of a combined rTMS and AIT intervention in children with ASD. The results will provide valuable insights into the neurotherapeutic potential of this combined approach and contribute to the development of evidence-based interventions for ASD.