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This study will determine the efficacy and safety of paired comprehensive behavioural intervention for tics (CBIT) plus repetitive transcranial magnetic stimulation (rTMS) treatment in children with Tourette\u2019s syndrome. We hypothesise that CBIT and active rTMS to the supplementary motor area (SMA) will (1) decrease tic severity, and (2) be associated with changes indicative of enhanced neuroplasticity (eg, changes in in vivo metabolite concentrations and TMS neurophysiology measures).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>This study will recruit 50 youth with TS, aged 6\u201318 for a phase II, double-blind, block randomised, sham-controlled trial comparing active rTMS plus CBIT to sham rTMS plus CBIT in a 1:1 ratio. The CBIT protocol is eight sessions over 10 weeks, once a week for 6 weeks and then biweekly. The rTMS protocol is 20 sessions of functional MRI-guided, low-frequency (1\u2009Hz) rTMS targeted to the bilateral SMA over 5 weeks (weeks 2\u20136). MRI, clinical and motor assessments and neurophysiological evaluations including motor mapping will be performed 1\u2009week before CBIT start, 1\u2009week after rTMS treatment and 1\u2009week after CBIT completion. The primary outcome measure is Tourette\u2019s symptom change from baseline to post-CBIT treatment, as measured by the Yale Global Tic Severity Scale. Secondary outcomes include changes in imaging, neurophysiological and behavioural markers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>Ethical approval by the Conjoint Health Research Ethics Board (REB18-0220). The results of this study will be published in peer-reviewed scientific journals, on ClinicalTrials.gov and shared with the Tourette and OCD Alberta Network. The results will also be disseminated through the Alberta Addictions and Mental Health Research Hub.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT03844919\">NCT03844919<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2021-053156","type":"journal-article","created":{"date-parts":[[2021,12,24]],"date-time":"2021-12-24T11:42:23Z","timestamp":1640346143000},"page":"e053156","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":13,"title":["Targeted Interventions in Tourette\u2019s using Advanced Neuroimaging and Stimulation (TITANS): study protocol for a double-blind, randomised controlled trial of transcranial magnetic stimulation (TMS) to the supplementary motor area in children with Tourette\u2019s syndrome"],"prefix":"10.1136","volume":"11","clinical-trial-number":[{"clinical-trial-number":"nct03844919","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02356003","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Cynthia K","family":"Kahl","sequence":"first","affiliation":[{"name":"Department of Psychiatry, University of Calgary, Calgary, Alberta, Canada"},{"name":"Department of Pediatrics, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rose","family":"Swansburg","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Calgary, Calgary, Alberta, Canada"},{"name":"Department of Pediatrics, University of Calgary, Calgary, Alberta, 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