Combined CBIT and rTMS to Improve Tourette's Syndrome

Not Applicable

Completed

Conditions: Tourette Syndrome

Interventions: Device: Transcranial Magnetic Stimulation
Behavioral: Comprehensive behavioral intervention

Registration Number: NCT04795908

Lead Sponsor: University of Florida

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 3

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Active rTMS Group	Transcranial Magnetic Stimulation	Patients will be seated in a comfortable reclined chair. The neurostimulation protocol will include 1-Hz rTMS over the bilateral SMA at 110% resting motor threshold (RMT). The SMA will be identified as 4 cm anterior to the vertex (Cz in standard 10-20 EEG setup). Each session will consist of 6 trains 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.
Active rTMS Group	Comprehensive behavioral intervention	Patients will be seated in a comfortable reclined chair. The neurostimulation protocol will include 1-Hz rTMS over the bilateral SMA at 110% resting motor threshold (RMT). The SMA will be identified as 4 cm anterior to the vertex (Cz in standard 10-20 EEG setup). Each session will consist of 6 trains 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.

Primary Outcome Measures

Name	Time	Method
Tic Severity	Through study completion, an average of 3 months	Tic severity will be measured with YGTSS. YGTSS is a clinician-rated scale used to assess tic severity, scored out of 100 where a higher score indicates greater tic frequency and severity. It includes a checklist of motor and vocal tics followed by an assessment of the number, frequency, intensity, complexity, and inference of motor tics and phonic tics - scored separately. Each of these dimensions is scored on a 0 to 5 scale. The YGTSS provides three tic severity scores: Total Motor (0 to 25); Total Phonic (0 to 25) and the combined Total Tic Severity Score (0 to 50), as well as a separate Impairment dimension scored from 0 to 50.

Secondary Outcome Measures

Name	Time	Method
Beck Anxiety Inventory (BAI)	Through study completion, an average of 3 months	This is a 21-question survey evaluation anxiety in patients on a 0 to 3 scale. Out of 63 points, where a higher score indicates a higher level of anxiety.
Modified Rush Videotape Tic Rating Scale (mRVTRS)	Through study completion, an average of 3 months	This is a tool used by an objective examiner to quantify the severity of a patient's tics by rating the number of body areas affected, motor tic frequency, phonic tic frequency, motor tic severity, and phonic tic severity, each on a 0 through 4 score by watching a video of the patient. Scored out of 20, where a higher score indicates greater tic severity.
High-Density EEG	12 weeks	High-Density EEG was measured while patients either allowed tics to come or actively suppressed tics
Beck Depression Inventory (BDI)	Through study completion, an average of 3 months	This is a 21-question survey evaluating depression in patients on a 0 to 3 scale. Scored out of 63 points, where a higher score indicates a higher level of depression.
Yale-Brown Obsessive Compulsive Scale (Y-BOCS)	Through study completion, an average of 3 months	This is a 10 question survey which rates components of obsessive thoughts or compulsive behavior and each question is rated on a 0 through 4 scale. Scored out of 40, where a higher score indicates higher levels of obsessive-compulsive tendencies.
Adult ADHD Self-Report Scale (ASRS)	Through study completion, an average of 3 months	This is an 18-question survey which asks patients to rate levels of attention, concentration, and organization as applied to daily tasks. Each question was assigned to a Likert scale of 1-5, where a higher number indicates a higher severity of that aspect of attention deficit. Individual responses were then summed together to obtain a Total Score ranging from 18-90, where a higher score indicates a higher impact of ADHD symptoms on daily functioning.
Gilles de la Tourette Syndrome - Quality of Life Scale (GTS-QOL)	Through study completion, an average of 3 months	This is a 27-question survey that asks patients to rate how their tics and abnormal movements affect their quality of life. When answers are converted to a Likert value of 1 through 5, the survey is scored out of 135, with higher scores indicating worse quality of life.