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

OBJECTIVES: 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. DESIGN: Multicentre randomised sham controlled trial. SETTING: Three academic hospitals across three provinces in China, conducted from July 2023 to October 2024. PARTICIPANTS: 200 children aged 4-10 years with autism spectrum disorder (167 boys and 33 girls) all with a full scale intelligence quotient ≥50. INTERVENTIONS: 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. MAIN OUTCOME MEASURES: 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. RESULTS: 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. CONCLUSIONS: 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. TRIAL REGISTRATION: ClinicalTrials.gov NCT05927792.