A Phase 2 interventional study of Transcranial Magnetic Stimulation (active) and Transcranial Magnetic Stimulation (sham) in Tourette Syndrome, sponsored by Yale University. Completed at 2 sites in United States. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2019-02-21.
Sponsored by Yale University · Phase 2, Interventional, and Treatment
This study will evaluate the clinical efficacy of 1 Hz repetitive transcranial magnetic stimulation (rTMS) applied to the supplementary motor area (SMA) in Tourette's Syndrome (TS) patients who have not fully responded to conventional therapies. The investigators will collect TMS measures of motor cortex excitability to test whether rTMS restores normal levels of intracortical inhibition found to be deficient in TS. The investigators will administer neuropsychological tests to demonstrate that SMA targeted rTMS can be administered safely without significant impairments of cognitive or motor functioning. The investigators hypothesize that:
This study tests the efficacy of repetitive Transcranial Magnetic Stimulation (rTMS) in the treatment of Tourette's Syndrome (TS). It also examines measures of brain function to study the brain basis underlying TS.
Despite major advances in the study and treatment of TS, patients often do not experience full remission from pharmacotherapy or behavioral therapy (Leckman 2002). rTMS is a non-invasive procedure that stimulates the brain using magnetic fields. This pilot study reported that rTMS may reduce TS symptoms (Mantovani et al., 2006). While promising, prior research has several limitations (e.g., relatively small sample sizes, and lack of sham [placebo] comparison).
This study addresses the drawbacks of prior work, and will provide data that will help to determine whether rTMS can be useful for TS patients resistant to conventional therapies. 25 outpatients with TS who have been only partially responsive to conventional therapies will be randomly assigned to either active low frequency (1 Hz) rTMS or sham (placebo) stimulation. The active or sham stimulation will be applied to the supplementary motor area (SMA) daily for three weeks. If rTMS will be added onto ongoing pharmacotherapy, the doses must have been stable for four weeks prior to study entry. The SMA was selected because of its connections with brain areas implicated in TS. Pilot work indicates that stimulation of SMA with low frequency rTMS is beneficial in TS patients. Low frequency rTMS has the added benefit of a better safety profile (i.e. no risk of seizure) than high frequency rTMS.
Rating scales for symptom change will be obtained at baseline, during the rTMS course, and at the end of three weeks of treatment. Patients will then be offered an open-label cross-over phase for an additional three weeks of daily active rTMS treatment. Patients who meet remission criteria in either phase or response criteria following the cross-over phase will continue routine clinical care under the supervision of their treating psychiatrist and will be invited back for assessment at 1, 3, and 6 months to determine the persistence of benefit.
Excitability of the motor cortex has been reported to be abnormal in TS, and may relate to dysfunction in motor pathways. We will collect measures of motor cortex excitability (with single and paired-pulse TMS) at baseline and after each phase to study whether changes in these measures may be correlated with clinical improvement.
220 studies on the registry are indexed under Tourette Syndrome; 37 are open to participants now.
This study's enrollment of 20 is below the median of 34 across 166 interventional studies indexed under Tourette Syndrome.
Browse Tourette Syndrome studies →Yale University is the lead sponsor of 1,724 studies on the registry; 298 are open to participants now.
Of its 210 completed or terminated interventional studies of FDA-regulated products, 126 (60%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Other exclusion criteria include those common to every TMS protocol:
Device: Transcranial Magnetic Stimulation (active)
Device: Transcranial Magnetic Stimulation (sham)
Magstim Rapid2 stimulator with Air Film Coil at 110% motor threshold at 1Hz for 30 minutes.
Also known as: Magstim Rapid2
Magstim Rapid2 stimulator with Sham Air Film Coil at 110% motor threshold at 1Hz for 30 minutes.
Also known as: Magstim Rapid2
Yale Global Tic Severity Scale (Y-GTSS)
Y-GTSS is a clinician-rated scale used to assess tic severity. Motor and phonic tics are rated separately from 0 to 5 on several scales including number, frequency, intensity, complexity, and interference. Thus Motor and Phonic Tic scores can range from 0 to 25; the combined Total Tic Score ranges from 0 to 50. There is also an Impairment score that rates the overall burden due to tics. The Impairment scale yields a single score from 0 to 50 with higher scores indicating higher levels of overall impairment associated with tics.
Time frame: 3 weeks
Motor Cortex Excitability Normalization-Right Motor Threshold
Motor Threshold (MT) is thought to be a measure of membrane excitability in pyramidal neurons. MT is defined as the minimum magnetic flux needed to elicit a threshold EMG response (50 µV in peak to peak amplitude) in a resting target muscle in 5 out of 10 trials using single pulse TMS administered to the contralateral primary motor cortex. MT for both right and left hand are determined, and the lowest is used to select the intensity for rTMS.
Time frame: 3 weeks
Number of Patients With "Much Improved or Very Much Improved" on Clinical Global Impression-Improvement (CGI) Scale
The CGI-I is a clinician-rated scales that have been used in clinical trials for over 25 years. Clinicians rate patient improvement compared to baseline. By convention, 4 = No Change; scores of 5, 6, and 7 move in the direction of worsening; scores of 3, 2, and 1 correspond to "Minimal Improvement," "Much Improved" or "Very Much Improved," respectively. CGI-I ratings of "Much" or "Very Much Improved" at post-treatment are used to identify treatment responders.
Time frame: 3 weeks
Motor Cortex Excitability Normalization-Left Motor Threshold
Motor Threshold (MT) is thought to be a measure of membrane excitability in pyramidal neurons. MT is defined as the minimum magnetic flux needed to elicit a threshold EMG response (50 µV in peak to peak amplitude) in a resting target muscle in 5 out of 10 trials using single pulse TMS administered to the contralateral primary motor cortex. MT for both right and left hand are determined, and the lowest is used to select the intensity for rTMS.
Time frame: 3 weeks
Number of Patients With "Improved or Minimally Improved" in Clinical Global Impression-Improvement (CGI) Scale
The CGI-I is a clinician-rated scales that have been used in clinical trials for over 25 years. Clinicians rate patient improvement compared to baseline. By convention, 4 = No Change; scores of 5, 6, and 7 move in the direction of worsening; scores of 3, 2, and 1 correspond to "Minimal Improvement," "Much Improved" or "Very Much Improved," respectively. CGI-I ratings of "Much" or "Very Much Improved" at post-treatment are used to identify treatment responders.
Time frame: 3 weeks
| Milestone | Active rTMS | Sham |
|---|---|---|
| Started | 9 | 11 |
| Completed | 8 | 10 |
| Not completed | 1 | 1 |
| Withdrew: Withdrawal by subject | 1 | 1 |
Y-GTSS is a clinician-rated scale used to assess tic severity. Motor and phonic tics are rated separately from 0 to 5 on several scales including number, frequency, intensity, complexity, and interference. Thus Motor and Phonic Tic scores can range from 0 to 25; the combined Total Tic Score ranges from 0 to 50. There is also an Impairment score that rates the overall burden due to tics. The Impairment scale yields a single score from 0 to 50 with higher scores indicating higher levels of overall impairment associated with tics.
| units on a scale | Active | Sham |
|---|---|---|
| Yale Global Tic Severity Scale (Y-GTSS) | 29.5 ± 11.9 | 31.5 ± 8.1 |
Motor Threshold (MT) is thought to be a measure of membrane excitability in pyramidal neurons. MT is defined as the minimum magnetic flux needed to elicit a threshold EMG response (50 µV in peak to peak amplitude) in a resting target muscle in 5 out of 10 trials using single pulse TMS administered to the contralateral primary motor cortex. MT for both right and left hand are determined, and the lowest is used to select the intensity for rTMS.
| µV | Active | Sham |
|---|---|---|
| Motor Cortex Excitability Normalization-Right Motor Threshold | 56 ± 16.3 | 59.8 ± 16.3 |
The CGI-I is a clinician-rated scales that have been used in clinical trials for over 25 years. Clinicians rate patient improvement compared to baseline. By convention, 4 = No Change; scores of 5, 6, and 7 move in the direction of worsening; scores of 3, 2, and 1 correspond to "Minimal Improvement," "Much Improved" or "Very Much Improved," respectively. CGI-I ratings of "Much" or "Very Much Improved" at post-treatment are used to identify treatment responders.
| participants | Active | Sham |
|---|---|---|
| Number of Patients With "Much Improved or Very Much Improved" on Clinical Global Impression-Improvement (CGI) Scale | 1 | 0 |
Motor Threshold (MT) is thought to be a measure of membrane excitability in pyramidal neurons. MT is defined as the minimum magnetic flux needed to elicit a threshold EMG response (50 µV in peak to peak amplitude) in a resting target muscle in 5 out of 10 trials using single pulse TMS administered to the contralateral primary motor cortex. MT for both right and left hand are determined, and the lowest is used to select the intensity for rTMS.
| µV | Active | Sham |
|---|---|---|
| Motor Cortex Excitability Normalization-Left Motor Threshold | 56.5 ± 12.8 | 63.8 ± 16.3 |
The CGI-I is a clinician-rated scales that have been used in clinical trials for over 25 years. Clinicians rate patient improvement compared to baseline. By convention, 4 = No Change; scores of 5, 6, and 7 move in the direction of worsening; scores of 3, 2, and 1 correspond to "Minimal Improvement," "Much Improved" or "Very Much Improved," respectively. CGI-I ratings of "Much" or "Very Much Improved" at post-treatment are used to identify treatment responders.
| participants | Active | Sham |
|---|---|---|
| Number of Patients With "Improved or Minimally Improved" in Clinical Global Impression-Improvement (CGI) Scale | 2 | 8 |
Collected over Adverse Events were collected throughout the duration of the study, which was approximately 4 years.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Active | — | 0/8 (0%) | 4/8 (50%) |
| Sham | — | 0/10 (0%) | 9/10 (90%) |
| Event | Active | Sham |
|---|---|---|
| Neck PainMusculoskeletal and connective tissue disorders | 2/8 | 9/10 |
| HeadacheNervous system disorders | 4/8 | 4/10 |
| Scalp PainSkin and subcutaneous tissue disorders | 2/8 | 2/10 |
| Trouble ConcentratingNervous system disorders | 0/8 | 1/10 |
| Age, Continuous(years) | Active | Sham | Total |
|---|---|---|---|
| Mean | 29.1 ± 7.4 | 39.0 ± 16.1 | 33.7 ± 12.1 |
| Sex: Female, Male(Participants) | Active | Sham | Total |
|---|---|---|---|
| Female | 2 | 2 | 4 |
| Male | 7 | 9 | 16 |
This study is completed, as verified in Feb 2019. You cannot join it, but the record below documents what was studied.
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