Repetitive transcranial magnetic stimulation in children and adolescents with autism spectrum disorder: study protocol for a double-blind, sham-controlled, randomized clinical trial.

Background: The prevalence of autism spectrum disorder (ASD) has significantly increased over recent decades, representing a serious public health issue. Neurobiological characteristics of ASD include imbalances in cortical excitation and inhibition, along with disruptions in neural network connectivity. Repetitive transcranial magnetic stimulation (rTMS) may provide a therapeutic option when cognitive-behavioral therapy alone is insufficient to alleviate core symptoms. This article outlines the protocol for a double-blind, sham-controlled, randomized study assessing low-frequency rTMS targeting the bilateral dorsolateral prefrontal cortex (DLPFC) in children and adolescents with ASD. The objective is to evaluate the efficacy of rTMS compared to sham stimulation.

Methods: Forty patients with ASD, aged 7-18 years and with different levels of clinical severity, will be randomized into an active treatment group (n = 20) and a sham control group (n = 20). Each participant will receive 18 low-frequency (2 Hz) rTMS sessions over 9 weeks, administered at 90% of the motor threshold with 180 pulses per session. Treatment will target the left DLPFC (six sessions), the right DLPFC (six sessions), and both hemispheres (six sessions). Clinical, cognitive, and neurophysiological assessments will be conducted at baseline, post-treatment, and 1-month follow-up. Biological samples (blood, urine) will be collected at each time point to evaluate changes in various biomarkers, including tryptophan metabolites, neurotrophic factors, neurotransmitters, and inflammatory mediators. Safety will be monitored through semi-structured interviews and adverse event reporting.

Discussion: This study aims to identify a safe rTMS protocol for ASD that could complement existing therapies. By assessing the cognitive domains and the clinical and biochemical profiles most responsive to rTMS, this study may contribute to optimize ASD treatments and enhance therapeutic outcomes in pediatric populations.

Trial registration: The study protocol is registered at "ClinicalTrials.gov" with the following ID: NCT06069323.