Teen and Adult Tic TMS Study
ConditionTic Disorder
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age15-35
SponsorUniversity of California, San Francisco
About this trial
This project investigates safety, tolerability, and efficacy signals of accelerated continuous theta burst stimulation (cTBS), a form of inhibitory repetitive transcranial magnetic stimulation (rTMS), for patients with Tourette Syndrome and chronic tic disorders (CTD). It integrates resting-state functional MRI (fMRI) to assess changes in brain circuits and neurophysiology. CTD are neurodevelopmental disorders marked by motor and/or vocal tics, associated with dysfunction in cortico-striato-thalamo-cortical (CSTC) networks, particularly the supplementary motor area (SMA), primary motor cortex (M1), and connected regions. While low-frequency rTMS has shown preliminary benefits in pediatric populations, circuit-targeted approaches remain relatively unexplored in children, adolescents and adults, leaving no consensus about optimal applications.
Participants will be randomized to receive 50 sessions of 1800 pulses of cTBS rTMS over two weeks, with five sessions/day targeting the SMA or M1. Assessments will include the Yale Global Tic Severity Scale (YGTSS) and MRI.
Aim 1 Determine if cTBS to the M1 can reduce CTD symptoms and normalize abnormal network connectivity within the Somato-Cognitive Action Network (SCAN).
Aim 2 Determine if cTBS to the SMA can reduce symptoms of CTD and normalize abnormal network connectivity within the Action Mode Network (AMN).
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Outpatients
Ages 15 - 35 years old
Meets DSM-5 criteria for persistent (chronic) vocal/motor tic disorder or Tourette's syndrome with screening YGTSS score ≥ 20 (moderate or greater severity).
Moderate severity or intolerable side effects with at least one prior trial of an evidence-based anti-tic medication.
Disqualifiers
Psychiatric: history of schizophrenia, bipolar disorder, substance /alcohol abuse disorder, current elevated suicide risk, prior psychosurgery.
Neurologic: severe neurocognitive disorder, seizure disorder, certain structural brain lesions (e.g., intracranial mass lesions, TBI, hydrocephalus, sequelae of meningitis, frank brain injury).
TMS contraindications: implanted device; presence of metal in the head, including eyes and ears (excluding dental implants); certain tics.
Subjects with an unstable physical, systemic, or metabolic disorder (e.g., unstable hypertension; malnutrition).
Trial design
Design model
Parallel
Treatments tested in this trial
cTBS (accelerated continuous theta burst stimulation)
DeviceParticipants will be randomized to receive 50 sessions of 1800 pulses of cTBS rTMS over two weeks, with five sessions/day targeting the SMA or M1.
Treatment groups
40 Participants
are divided into 2 treatment groupsGroup A: M1 (primary motor cortex)Experimental treatment 1 intervention
Group B: SMA (supplementary motor area)Experimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
To assess the safety and tolerability of repeated theta burst TMS administration in adolescents age 15 - 35 years with CTD.
This study's primary aim is to determine the safety and tolerability of repeated TMS administration in adolescents and adults ages 15 - 35 years with DSM-5 confirmed CTD of moderate or greater severity. These will be determined by protocol completion rate from enrollment to final visit, and tabulation of the individual and summed frequencies of reported and identified adverse events observed from study enrollment to final visit.
Time frame
All protocol visits (treatment days 1 - 10)Secondary outcomes
1
To examine the possible efficacy of repeated TMS administration on CTD symptom severity at two different brain regions (M1 and SMA).
The secondary objective of the project is to examine if repeated TMS administration at two different brain regions (M1 and SMA) is associated with clinically significant decreases in CTD symptom severity, as measured by repeated administration of the Yale Global Tic Severity Scale (YGTSS) by a trained clinical rater.
Time frame
Screening, baseline, treatment day 5, treatment day 10, 1-week follow-up, 1-month follow-upOther outcomes
1
Change in Clinical Global Impression-Severity Scale (CGI-S) pre- vs post-TMS
At the clinical level, the investigators will identify possible early clinical efficacy signals of accelerated cTBS in reducing tics and related symptoms. Clinical outcomes will be assessed using Clinical Global Impression-Severity Scale (CGI-S). The investigators will examine within-subject changes from baseline to post-treatment and compare response patterns across stimulation targets.
Time frame
Baseline, treatment day 5, treatment day 10, 1-week follow-up, 1-month follow-up2
Change in Clinical Global Impression-Improvement Scale (CGI-I) pre- vs post-TMS
At the clinical level, the investigators will identify possible early clinical efficacy signals of accelerated cTBS in reducing tics and related symptoms. Clinical outcomes will be assessed using Clinical Global Impression-Improvement Scale (CGI-I). The investigators will examine within-subject changes from baseline to post-treatment and compare response patterns across stimulation targets.
Time frame
Baseline, treatment day 5, treatment day 10, 1-week follow-up, 1-month follow-up3
Change in functional connectivity pre- vs post-TMS
The investigators will explore whether pre-treatment fMRI features differentiate responders from non-responders, providing early insight into potential neural predictors of cTBS efficacy. Using our pre- and post-treatment resting state fMRI measures of functional connectivity between the TMS target of SMA vs M1 and other nodes, the investigators will determine if a pattern of baseline fcrsMRI activity or change over time is correlated with CTD symptom change with treatment. The investigators will conduct resting state fMRI (RS-fMRI) scans at baseline (before TMS) and one week following completion of TMS (approximately 3 weeks after baseline). The investigators will identify associations of functional connectivity using SMA and M1- thumb seeds with clinical symptom response.
Time frame
From time of enrollment to one week follow up after end of treatment (Week 4)Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Source ClinicalTrials.gov