The CBIT+TMS Trial: study protocol for a two-phase randomized controlled trial testing neuromodulation to augment behavior therapy for youth with chronic tics.

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 patient 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, noninvasive 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 (1Hz 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 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. 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 Identifier: NCT04578912.

Déclaration de conflit d'intérêts

Competing interests {28} CC has received speaking honoraria and travel reimbursement from the Tourette Association of America (TAA), salary support from the University of Minnesota MnDRIVE initiative, and research funding from the US National Institutes of Health (NIH), National Science Foundation (NSF), Minnesota Robotics Institute, Masonic Charities, and Posit Science via NIH-funded grants (R43MH121209, R43MH124542). AO is an inventor on patents and patent applications describing methods and devices for non-invasive brain stimulation. AO has equity in the startup StimPhase which develops brain stimulation technologies. AO has received research funding from the NIH, NSF, the University of Minnesota MnDRIVE Initiative, and the Minnesota Partnership for Biotechnology & Medical Genomics. MF has received research funding from the NIH. DJG has served as a consultant for Turing Medical, the developers of FIRMM software, and has received research funding from the NIH. KL has received research funding from the NIH and Department of Veterans Affairs. SJ has received grant support from the NIH, Department of Defense (DOD), SFARI Foundation, and Roche; and has attended advisory boards for Fraser, Roche, and Minnesota Independence College & Community. JA, KH, SH, BW, SF, BM, AT, TH, and MC declare that they have no competing interests.