Repetitive transcranial magnetic stimulation (rTMS) in autism spectrum disorder: protocol for a multicentre randomised controlled clinical trial

Abstract

Introduction: There are no well-established biomedical treatments for the core symptoms of autism spectrum disorder (ASD). A small number of studies suggest that repetitive transcranial magnetic stimulation (rTMS), a non-invasive brain stimulation technique, may improve clinical and cognitive outcomes in ASD. We describe here the protocol for a funded multicentre randomised controlled clinical trial to investigate whether a course of rTMS to the right temporoparietal junction (rTPJ), which has demonstrated abnormal brain activation in ASD, can improve social communication in adolescents and young adults with ASD.; Methods and Analysis: This study will evaluate the safety and efficacy of a 4-week course of intermittent theta burst stimulation (iTBS, a variant of rTMS) in ASD. Participants meeting criteria for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition ASD (n=150, aged 14-40 years) will receive 20 sessions of either active iTBS (600 pulses) or sham iTBS (in which a sham coil mimics the sensation of iTBS, but no active stimulation is delivered) to the rTPJ. Participants will undergo a range of clinical, cognitive, epi/genetic, and neurophysiological assessments before and at multiple time points up to 6 months after iTBS. Safety will be assessed via a structured questionnaire and adverse event reporting. The study will be conducted from November 2020 to October 2024.; Ethics and Dissemination: The study was approved by the Human Research Ethics Committee of Monash Health (Melbourne, Australia) under Australia's National Mutual Acceptance scheme. The trial will be conducted according to Good Clinical Practice, and findings will be written up for scholarly publication.; Trial Registration Number: Australian New Zealand Clinical Trials Registry (ACTRN12620000890932). (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)Autism Res. 2016 Feb;9(2):184-203. (PMID: 26536383); Neuroimage. 2011 Jun 1;56(3):1832-8. (PMID: 21356316); Neuropharmacology. 2013 May;68:202-9. (PMID: 22727823); Neurosci Biobehav Rev. 2012 Feb;36(2):901-42. (PMID: 22101112); Psychiatry Clin Neurosci. 2018 Apr;72(4):195-211. (PMID: 29292553); Clin Neurophysiol. 2009 Dec;120(12):2008-2039. (PMID: 19833552); J Autism Dev Disord. 2016 Mar;46(3):954-63. (PMID: 26520145); Headache. 2019 Oct;59(9):1436-1447. (PMID: 31535368); Neuroimage. 2017 Nov 15;162:289-296. (PMID: 28912081); Brain Stimul. 2020 May - Jun;13(3):565-575. (PMID: 32289678); Neuroimage. 2017 Mar 1;148:1-7. (PMID: 28062252); Nat Genet. 2019 Mar;51(3):431-444. (PMID: 30804558); Biol Psychiatry. 2019 Feb 15;85(4):e21-e22. (PMID: 30103951); Brain Stimul. 2018 Sep - Oct;11(5):1110-1118. (PMID: 29885862); Hum Brain Mapp. 2016 Nov;37(11):3957-3978. (PMID: 27329401); Clin Child Fam Psychol Rev. 2011 Sep;14(3):302-17. (PMID: 21735077); Front Psychiatry. 2017 Jan 04;7:205. (PMID: 28101064); Autism. 2020 Feb;24(2):297-306. (PMID: 31238701); Curr Opin Psychiatry. 2010 Mar;23(2):85-90. (PMID: 20061953); MMWR Surveill Summ. 2018 Apr 27;67(6):1-23. (PMID: 29701730); J Child Adolesc Psychopharmacol. 2016 Sep;26(7):606-16. (PMID: 27284688); Psychol Med. 2019 Mar;49(4):559-572. (PMID: 30178724); Brain Stimul. 2014 Mar-Apr;7(2):206-11. (PMID: 24280031); J Biomed Inform. 2019 Jul;95:103208. (PMID: 31078660); Psychophysiology. 2019 Jun;56(6):e13336. (PMID: 30710345); Front Integr Neurosci. 2018 Jul 09;12:27. (PMID: 30038561); BMC Pediatr. 2018 Aug 27;18(1):284. (PMID: 30149807); Brain Stimul. 2020 May - Jun;13(3):539-547. (PMID: 32289673); Arch Gen Psychiatry. 2010 May;67(5):507-16. (PMID: 20439832); Nat Rev Neurosci. 2012 Apr 13;13(5):336-49. (PMID: 22498897); Biol Psychiatry. 2012 Mar 1;71(5):427-33. (PMID: 21974786); Int Rev Psychiatry. 2018 Feb;30(1):25-39. (PMID: 29537331); Curr Neuropharmacol. 2019;17(8):787-807. (PMID: 30963971); J Autism Dev Disord. 2018 Jul;48(7):2350-2367. (PMID: 29453710); Netw Neurosci. 2018 Nov 01;3(1):157-172. (PMID: 30793079); Clin Neurophysiol. 2019 Aug;130(8):1409-1416. (PMID: 31104898); Front Neurol. 2018 Jul 24;9:556. (PMID: 30087648); Neurosci Biobehav Rev. 2012 Oct;36(9):2044-55. (PMID: 22841562). Linking ISSN: 20446055. Subset: MEDLINE; Date of Electronic Publication: 2021 Jul 07. ; Original Imprints: Publication: [London] : BMJ Publishing Group Ltd, 2011- <br />