Trial Outcomes & Findings for Combined CBIT and rTMS to Improve Tourette's Syndrome (NCT NCT04795908)

NCT ID: NCT04795908

Last Updated: 2024-04-30

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 3 participants
• Primary outcome timeframe: Through study completion, an average of 3 months
• Results posted on: 2024-04-30

Participant Flow

Participant milestones

Measure	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. The 3 patients recruited for this study were assigned to this active rTMS group.
Overall Study STARTED	3
Overall Study COMPLETED	3
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Combined CBIT and rTMS to Improve Tourette's Syndrome

Baseline characteristics by cohort

Measure	Active rTMS Group n=3 Participants 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.
Age, Categorical <=18 years	1 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	24.67 years n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	3 participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Baseline n=3 Participants 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.	Post-TMS (Approximately 1 Week) n=3 Participants Captured following completion of rTMS, approximately 1 week after baseline.	Post-CBIT (Approximately 11 Weeks) n=3 Participants Captured following tele-CBIT intervention, approximately 11 weeks after baseline.
Tic Severity	59.3 score on a scale Interval 50.0 to 76.0	43.3 score on a scale Interval 29.0 to 49.0	37.67 score on a scale Interval 26.0 to 48.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Baseline n=3 Participants 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.	Post-TMS (Approximately 1 Week) n=3 Participants Captured following completion of rTMS, approximately 1 week after baseline.	Post-CBIT (Approximately 11 Weeks) n=3 Participants Captured following tele-CBIT intervention, approximately 11 weeks after baseline.
Modified Rush Videotape Tic Rating Scale (mRVTRS)	16.5 score on a scale Interval 13.5 to 19.5	12.33 score on a scale Interval 11.0 to 15.0	9.5 score on a scale Interval 6.5 to 13.5

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Baseline n=3 Participants 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.	Post-TMS (Approximately 1 Week) n=3 Participants Captured following completion of rTMS, approximately 1 week after baseline.	Post-CBIT (Approximately 11 Weeks) n=3 Participants Captured following tele-CBIT intervention, approximately 11 weeks after baseline.
Beck Depression Inventory (BDI)	17 score on a scale Interval 8.0 to 26.0	12 score on a scale Interval 7.0 to 21.0	11.3 score on a scale Interval 7.0 to 17.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Baseline n=3 Participants 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.	Post-TMS (Approximately 1 Week) n=3 Participants Captured following completion of rTMS, approximately 1 week after baseline.	Post-CBIT (Approximately 11 Weeks) n=3 Participants Captured following tele-CBIT intervention, approximately 11 weeks after baseline.
Beck Anxiety Inventory (BAI)	21.67 score on a scale Interval 10.0 to 39.0	17 score on a scale Interval 8.0 to 32.0	18 score on a scale Interval 11.0 to 29.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Baseline n=3 Participants 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.	Post-TMS (Approximately 1 Week) n=3 Participants Captured following completion of rTMS, approximately 1 week after baseline.	Post-CBIT (Approximately 11 Weeks) n=3 Participants Captured following tele-CBIT intervention, approximately 11 weeks after baseline.
Yale-Brown Obsessive Compulsive Scale (Y-BOCS)	17 score on a scale Interval 13.0 to 21.0	18.3 score on a scale Interval 12.0 to 22.0	20 score on a scale Interval 14.0 to 28.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Baseline n=3 Participants 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.	Post-TMS (Approximately 1 Week) n=3 Participants Captured following completion of rTMS, approximately 1 week after baseline.	Post-CBIT (Approximately 11 Weeks) n=3 Participants Captured following tele-CBIT intervention, approximately 11 weeks after baseline.
Adult ADHD Self-Report Scale (ASRS)	70.67 score on a scale Interval 70.0 to 72.0	64.33 score on a scale Interval 60.0 to 68.0	62 score on a scale Interval 59.0 to 65.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Baseline n=3 Participants 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.	Post-TMS (Approximately 1 Week) n=3 Participants Captured following completion of rTMS, approximately 1 week after baseline.	Post-CBIT (Approximately 11 Weeks) n=3 Participants Captured following tele-CBIT intervention, approximately 11 weeks after baseline.
Gilles de la Tourette Syndrome - Quality of Life Scale (GTS-QOL)	87.33 score on a scale Interval 80.0 to 100.0	67.67 score on a scale Interval 60.0 to 78.0	64.67 score on a scale Interval 57.0 to 74.0

SECONDARY outcome

Timeframe: 12 weeks

Population: Unable to be completed due to technical limitations

High-Density EEG was measured while patients either allowed tics to come or actively suppressed tics

Outcome measures

Outcome data not reported

Adverse Events

Baseline

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Post-TMS

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Post-CBIT

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Baseline n=3 participants at risk Prior to TMS	Post-TMS n=3 participants at risk follow rTMS	Post-CBIT n=3 participants at risk following tele-CBIT
Nervous system disorders Headache	0.00% 0/3 • 11-12 weeks	100.0% 3/3 • Number of events 3 • 11-12 weeks	0.00% 0/3 • 11-12 weeks

Additional Information

Jessica Frey

West Virginia University

Phone: 304-598-6127

Email: jessica.frey@hsc.wvu.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place