Accelerated continuous theta burst stimulation targeting left primary motor cortex for children with autism spectrum disorder: multicentre randomised sham controlled trial.

Abstract

To investigate the efficacy and safety of a five day accelerated continuous theta burst stimulation (a-cTBS) protocol in improving social communication impairment in children with autism spectrum disorder. Multicentre randomised sham controlled trial. Three academic hospitals across three provinces in China, conducted from July 2023 to October 2024. 200 children aged 4-10 years with autism spectrum disorder (167 boys and 33 girls) all with a full scale intelligence quotient ≥50. Participants were randomised 1:1 to receive active a-cTBS (n=100) or sham (n=100) treatment stratified by full scale intelligence quotient (≥70 or <70) and study site. Participants received 10 sessions each day for five consecutive days, targeting the left primary motor cortex. Participants and evaluators were masked to interventions. Two primary outcomes were assessed using the Social Responsiveness Scale, second edition (SRS-2): changes in social communication impairment from baseline to post-intervention and from baseline to one month follow-up. Primary analyses were conducted on a modified intention-to-treat population, including participants who received at least one stimulation session. Secondary outcomes included language improvements assessed from baseline to one month follow-up and changes in SRS-2 subscales. Of the 200 participants, 198 were included in the modified intention-to-treat analysis (99 in each group) and 193 completed the full intervention. Compared with the sham group, the a-cTBS group showed significantly greater reductions in SRS-2 scores post-intervention (-6.25, 95% confidence interval -8.69 to -3.81; Cohen's d -0.92; P<0.001) and at one month follow-up (-6.17, -8.65 to -3.70; -0.90; P<0.001). Secondary outcomes also favoured a-cTBS, with significant improvements observed in language abilities (Cohen's d 0.12-0.47; all P<0.02; measured by Multilingual Assessment Instrument for Narratives). Reported adverse events were all mild to moderate and resolved without intervention. A five day a-cTBS protocol targeting the left primary motor cortex significantly improved social communication in children with autism spectrum disorder and showed a favourable safety profile. These findings support a-cTBS as a viable and scalable therapeutic option for children with autism spectrum disorder. ClinicalTrials.gov NCT05927792.