The CBIT + TMS trial: study protocol for a two-phase randomized controlled trial testing neuromodulation to augment behavior therapy for youth with chronic tics
Christine Conelea,
Deanna J. Greene,
Jennifer Alexander,
Kerry Houlihan,
Sarah Hodapp,
Brianna Wellen,
Sunday Francis,
Bryon Mueller,
Tim Hendrickson,
Angela Tseng,
Mo Chen,
Mark Fiecas,
Kelvin Lim,
Alexander Opitz,
Suma Jacob
Affiliations
Christine Conelea
Department of Psychiatry and Behavioral Sciences, Masonic Institute for the Developing Brain, University of Minnesota
Deanna J. Greene
Department of Cognitive Science, University of California San Diego
Jennifer Alexander
Department of Psychiatry and Behavioral Sciences, Masonic Institute for the Developing Brain, University of Minnesota
Kerry Houlihan
Department of Psychiatry and Behavioral Sciences, Masonic Institute for the Developing Brain, University of Minnesota
Sarah Hodapp
Department of Psychiatry and Behavioral Sciences, Masonic Institute for the Developing Brain, University of Minnesota
Brianna Wellen
Department of Psychiatry and Behavioral Sciences, Masonic Institute for the Developing Brain, University of Minnesota
Sunday Francis
Department of Psychiatry and Behavioral Sciences, University of Minnesota
Bryon Mueller
Department of Psychiatry and Behavioral Sciences, University of Minnesota
Tim Hendrickson
Masonic Institute for the Developing Brain, University of Minnesota Informatics Institute
Angela Tseng
Department of Psychiatry and Behavioral Sciences, Masonic Institute for the Developing Brain, University of Minnesota
Mo Chen
Department of Psychiatry and Behavioral Sciences, University of Minnesota
Mark Fiecas
School of Public Health, Division of Biostatistics, University of Minnesota
Kelvin Lim
Department of Psychiatry and Behavioral Sciences, University of Minnesota
Alexander Opitz
Department of Biomedical Engineering, University of Minnesota
Suma Jacob
Department of Psychiatry and Behavioral Sciences, University of Minnesota
Abstract Background Comprehensive Behavioral Intervention for Tics (CBIT) is a first-line treatment for tic disorders that aims to improve controllability over tics that an individual finds distressing or impairing. However, it is only effective for approximately half of patients. Supplementary motor area (SMA)-directed neurocircuitry plays a strong role in motor inhibition, and activity in this region is thought to contribute to tic expression. Targeted modulation of SMA using transcranial magnetic stimulation (TMS) may increase CBIT efficacy by improving patients' ability to implement tic controllability behaviors. Methods The CBIT + TMS trial is a two-phase, milestone-driven early-stage randomized controlled trial. The trial will test whether augmenting CBIT with inhibitory, non-invasive stimulation of SMA with TMS modifies activity in SMA-mediated circuits and enhances tic controllability in youth ages 12–21 years with chronic tics. Phase 1 will directly compare two rTMS augmentation strategies (1 Hz rTMS vs. cTBS) vs. sham in N = 60 participants. Quantifiable, a priori “Go/No Go Criteria” guide the decision to proceed to phase 2 and the selection of the optimal TMS regimen. Phase 2 will compare the optimal regimen vs. sham and test the link between neural target engagement and clinical outcomes in a new sample of N = 60 participants. Discussion This clinical trial is one of few to date testing TMS augmentation of therapy in a pediatric sample. The results will provide insight into whether TMS is a potentially viable strategy for enhancing CBIT efficacy and reveal potential neural and behavioral mechanisms of change. Trial registration ClinicalTrials.gov NCT04578912 . Registered on October 8, 2020.
