Tourette Syndrome
Conditions
Keywords
TMS, Transcranial magnetic stimulation, CBIT, Comprehensive Behavioral Intervention for Tics, Tourette Syndrome
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.
Interventions
DEVICETranscranial Magnetic Stimulation
rTMS will be delivered using a MagStim Super Rapid2 TMS therapy system.
BEHAVIORALComprehensive behavioral intervention
Patients will receive CBIT with a therapist trained in CBIT. Each session will last about an hour and will be delivered remotely via telemedicine. Sessions will be tailed to the patient's individual needs.
Sponsors
University of Florida
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| High-Density EEG | 12 weeks | High-Density EEG was measured while patients either allowed tics to come or actively suppressed tics |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active rTMS Group 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.
Transcranial Magnetic Stimulation: rTMS will be delivered using a MagStim Super Rapid2 TMS therapy system.
Comprehensive behavioral intervention: Patients will receive CBIT with a therapist trained in CBIT. Each session will last about an hour and will be delivered remotely via telemedicine. Sessions will be tailed to the patient's individual needs. | 3 |
| Total | 3 |
Baseline characteristics
| Characteristic | Active rTMS Group |
|---|---|
| Age, Categorical <=18 years | 1 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Age, Continuous | 24.67 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Region of Enrollment United States | 3 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 3 |
| other Total, other adverse events | 0 / 3 | 3 / 3 | 0 / 3 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 0 / 3 |
Outcome results
Primary
Tic Severity
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.
Time frame: Through study completion, an average of 3 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Baseline | Tic Severity | 59.3 score on a scale |
| Post-TMS (Approximately 1 Week) | Tic Severity | 43.3 score on a scale |
| Post-CBIT (Approximately 11 Weeks) | Tic Severity | 37.67 score on a scale |
p-value: 0.1997ANOVA
Secondary
Adult ADHD Self-Report Scale (ASRS)
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.
Time frame: Through study completion, an average of 3 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Baseline | Adult ADHD Self-Report Scale (ASRS) | 70.67 score on a scale |
| Post-TMS (Approximately 1 Week) | Adult ADHD Self-Report Scale (ASRS) | 64.33 score on a scale |
| Post-CBIT (Approximately 11 Weeks) | Adult ADHD Self-Report Scale (ASRS) | 62 score on a scale |
p-value: 0.0288ANOVA
Secondary
Beck Anxiety Inventory (BAI)
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.
Time frame: Through study completion, an average of 3 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Baseline | Beck Anxiety Inventory (BAI) | 21.67 score on a scale |
| Post-TMS (Approximately 1 Week) | Beck Anxiety Inventory (BAI) | 17 score on a scale |
| Post-CBIT (Approximately 11 Weeks) | Beck Anxiety Inventory (BAI) | 18 score on a scale |
p-value: 0.8984ANOVA
Secondary
Beck Depression Inventory (BDI)
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.
Time frame: Through study completion, an average of 3 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Baseline | Beck Depression Inventory (BDI) | 17 score on a scale |
| Post-TMS (Approximately 1 Week) | Beck Depression Inventory (BDI) | 12 score on a scale |
| Post-CBIT (Approximately 11 Weeks) | Beck Depression Inventory (BDI) | 11.3 score on a scale |
p-value: 0.6228ANOVA
Secondary
Gilles de la Tourette Syndrome - Quality of Life Scale (GTS-QOL)
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.
Time frame: Through study completion, an average of 3 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Baseline | Gilles de la Tourette Syndrome - Quality of Life Scale (GTS-QOL) | 87.33 score on a scale |
| Post-TMS (Approximately 1 Week) | Gilles de la Tourette Syndrome - Quality of Life Scale (GTS-QOL) | 67.67 score on a scale |
| Post-CBIT (Approximately 11 Weeks) | Gilles de la Tourette Syndrome - Quality of Life Scale (GTS-QOL) | 64.67 score on a scale |
p-value: 0.0524ANOVA
Secondary
High-Density EEG
High-Density EEG was measured while patients either allowed tics to come or actively suppressed tics
Time frame: 12 weeks
Population: Unable to be completed due to technical limitations
Secondary
Modified Rush Videotape Tic Rating Scale (mRVTRS)
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.
Time frame: Through study completion, an average of 3 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Baseline | Modified Rush Videotape Tic Rating Scale (mRVTRS) | 16.5 score on a scale |
| Post-TMS (Approximately 1 Week) | Modified Rush Videotape Tic Rating Scale (mRVTRS) | 12.33 score on a scale |
| Post-CBIT (Approximately 11 Weeks) | Modified Rush Videotape Tic Rating Scale (mRVTRS) | 9.5 score on a scale |
p-value: 0.076ANOVA
Secondary
Yale-Brown Obsessive Compulsive Scale (Y-BOCS)
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.
Time frame: Through study completion, an average of 3 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Baseline | Yale-Brown Obsessive Compulsive Scale (Y-BOCS) | 17 score on a scale |
| Post-TMS (Approximately 1 Week) | Yale-Brown Obsessive Compulsive Scale (Y-BOCS) | 18.3 score on a scale |
| Post-CBIT (Approximately 11 Weeks) | Yale-Brown Obsessive Compulsive Scale (Y-BOCS) | 20 score on a scale |
p-value: 0.8188ANOVA