TY - JOUR
T1 - Targeted Interventions in Tourette's using Advanced Neuroimaging and Stimulation (TITANS)
T2 - Study protocol for a double-blind, randomised controlled trial of transcranial magnetic stimulation (TMS) to the supplementary motor area in children with Tourette's syndrome
AU - Kahl, Cynthia K.
AU - Swansburg, Rose
AU - Kirton, Adam
AU - Pringsheim, Tamara
AU - Wilcox, Gabrielle
AU - Zewdie, Ephrem
AU - Harris, Ashley
AU - Croarkin, Paul E.
AU - Nettel-Aguirre, Alberto
AU - Chenji, Sneha
AU - MacMaster, Frank P.
N1 - Funding Information:
This study does not have a data monitoring committee. The investigative team, particularly the study coordinator, will be responsible for ensuring data are complete and accurately entered. Inter-rater reliability will be performed for assessment protocols, and integrity ratings will be made on 10% of CBIT sessions via video recording akin to Piacentini et al.37 Protocol modifications will be approved by the local research ethics board and logged on ClinicalTrials.gov. When appropriate, changes will be communicated to participants (eg, a change in assessment tool or study timeline). The study is supported by grant funding, which plays no role in data monitoring or auditing.
Funding Information:
Funding This work is primarily supported through a project grant from the Canadian Institute for Health Research (FM: principal investigator). Pilot study operating support came from the Hotchkiss Brain Institute/Mathison Centre for Mental Health Research & Education Pilot Research Fund (PFUN) Program. Trainee support came from the Branch Out Neurological Foundation, the Harley Hotchkiss – Samuel Weiss Postdoctoral Scholarship and support for the Scientific Director (FM) from Alberta Health Services. Equipment support came from the Alberta Children’s Hospital Foundation and the Canadian Foundation for Innovation Leaders Opportunity Fund.
Publisher Copyright:
© 2021 BMJ Publishing Group. All rights reserved.
PY - 2021/12/24
Y1 - 2021/12/24
N2 - Introduction Tourette's syndrome (TS) affects approximately 1% of children. 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's 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). Methods and analysis This study will recruit 50 youth with TS, aged 6-18 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 Hz) rTMS targeted to the bilateral SMA over 5 weeks (weeks 2-6). MRI, clinical and motor assessments and neurophysiological evaluations including motor mapping will be performed 1 week before CBIT start, 1 week after rTMS treatment and 1 week after CBIT completion. The primary outcome measure is Tourette's 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. Ethics and dissemination 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. Trial registration NCT03844919.
AB - Introduction Tourette's syndrome (TS) affects approximately 1% of children. 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's 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). Methods and analysis This study will recruit 50 youth with TS, aged 6-18 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 Hz) rTMS targeted to the bilateral SMA over 5 weeks (weeks 2-6). MRI, clinical and motor assessments and neurophysiological evaluations including motor mapping will be performed 1 week before CBIT start, 1 week after rTMS treatment and 1 week after CBIT completion. The primary outcome measure is Tourette's 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. Ethics and dissemination 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. Trial registration NCT03844919.
KW - child & adolescent psychiatry
KW - developmental neurology & neurodisability
KW - paediatric neurology
KW - protocols & guidelines
UR - http://www.scopus.com/inward/record.url?scp=85122544318&partnerID=8YFLogxK
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U2 - 10.1136/bmjopen-2021-053156
DO - 10.1136/bmjopen-2021-053156
M3 - Article
C2 - 34952879
AN - SCOPUS:85122544318
SN - 2044-6055
VL - 11
JO - BMJ Open
JF - BMJ Open
IS - 12
M1 - 053156
ER -