Clinical trial NCT04795908: Combined CBIT and rTMS to Improve Tourette's Syndrome
Official title: STOP-TIC Study: Strengthening Tourette Treatment OPtions Using TMS to Improve CBIT
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Tourette Syndrome
Keywords: TMS
Transcranial magnetic stimulation
CBIT
Comprehensive Behavioral Intervention for Tics
Tourette Syndrome
Lead sponsor: University of Florida
Sponsor class: OTHER
First posted: 2021-03-12
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The investigator will apply 16 sessions of repetitive transcranial magnetic stimulation (rTMS) over 4 consecutive days for adult patients suffering from Tourette's Syndrome. Following rTMS, patients will undergo 8 sessions of Comprehensive Behavioral Intervention for Tics (CBIT) over 10 weeks via telemedicine. Clinical improvement in tic severity will be the primary outcome measure. Secondary outcome measures including underlying physiological effects will be measured via functional magnetic resonance imaginge (fMRI), high-density electroencephalograhy (HD-EEG), and TMS.

Detailed description: Patients will be randomly assigned to active or sham stimulation, with 10 in each group, followed by 10 weeks of tele-CBIT. Patients will have primary and secondary outcome measures performed at four time points: Baseline (T0), following rTMS (T1), following CBIT (T2), and 1 month later (T3). The rTMS protocol will consist of 6 trains targeted to the supplementary motor area (SMA) lasting 5 minutes each (300 pulses per train) with an intertrain interval of 1 minute for a total duration of 35 minutes (1800 pulses). Patients will receive 4 sessions each day on 4 consecutive days for a total of 16 sessions. Daily duration of this study protocol should last approximately 170 minutes including a 10 minute break in between each session. The sham protocol will be the same except a sham coil will be used instead of an active coil. Following rTMS, patients will undergo 10 weeks of tele-CBIT.

The following outcome measures will be collected at four timepoints (T0, T1, T2, and T3):

Tics will be examined with the standardized Yale Global Tic Severity Scale (YGTSS) and the modified Rush Videotape Tic Rating Scale (mRVTRS), and co-morbid symptoms with the Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and Adult ADHD Self-Reports Scale (ASRS). Quality of life will be assessed with the Gilles de la Tourette Syndrome - Quality of Life scale (GTS-QOL).

TMS measures: A single-pulse of TMS will be targeted over the motor cortex to generate a motor evoked potential (MEP), which can be captured on EMG. The rest of the EMG will be analyzed to assess the time between the TMS pulse and the MEP (also known as the latency) and the amount of time muscle activity remains silent following the MEP (also known as the cortical silent period). In a paired-pulse TMS paradigm, a subthreshold pulse will be provided followed by an interstimulus interval and then subsequent delivery of a suprathreshold pulse. When the interstimulus interval is short (1-4 msec), the ratio of MEP amplitudes produced by these two pulses is known as short interval intracortical inhibition (SICI).

fMRI measure: Functional MRI will be used to record Blood Oxygen Level Dependent (BOLD) activity changes in patients at rest.

HD-EEG measure: A 128-electrode cap will be used to assess electrical activity in patients at rest and actively trying to suppress their tics.

Eligibility criteria: Inclusion Criteria:

* Any patient diagnosed with Tourette Syndrome \> 18 years of age with moderate tic severity.
* Participants will be allowed to continue oral medications that they are taking for TS concurrently but will not be allowed to change their concurrent medication regimen throughout the duration of the study

Exclusion Criteria:

* Presence of metallic objects or neurostimulators in the brain
* Pregnancy
* History of active seizures or epilepsy
* Contraindications to receiving fMRI, such as claustrophobia
* Inability to participate in CBIT due to other underlying cognitive or medical condition

Primary outcomes:
measure: Tic Severity
timeFrame: Through study completion, an average of 3 months
Secondary outcomes:
measure: Modified Rush Videotape Tic Rating Scale (mRVTRS)
timeFrame: Through study completion, an average of 3 months
measure: Beck Depression Inventory (BDI)
timeFrame: Through study completion, an average of 3 months
measure: Beck Anxiety Inventory (BAI)
timeFrame: Through study completion, an average of 3 months
measure: Yale-Brown Obsessive Compulsive Scale (Y-BOCS)
timeFrame: Through study completion, an average of 3 months
measure: Adult ADHD Self-Report Scale (ASRS)
timeFrame: Through study completion, an average of 3 months
measure: Gilles de la Tourette Syndrome - Quality of Life Scale (GTS-QOL)
timeFrame: Through study completion, an average of 3 months
measure: High-Density EEG
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: Fixel Neurologic Institute
state: Florida
Study officials:
affiliation: University of Florida
name: Aparna Wagle Shukla, MD
role: PRINCIPAL_INVESTIGATOR
References: