Tourette SyndromePhase 2TMSNCT00529308
Transcranial Magnetic Stimulation (TMS) for Individuals With Tourette's Syndrome
A Phase 2 study testing Transcranial Magnetic Stimulation (active) in people with Tourette Syndrome, run by Yale University at 2 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Tourette Syndrome
- What is being tested?
- Transcranial Magnetic Stimulation (active)
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 2 sitesUnited States
- Study dates
- Jul 2007to Jul 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Primary diagnosis of Tourette's Syndrome, as confirmed by the DSM-IV-TR criteria
- Residual TS symptoms, defined as a total Y-GTSS total motor tic or phonic tic score > 20, despite treatment with an adequate trial of medications (defined as a failure to respond to a trial of commonly used medications for TS such as clonidine, guanfacine, or neuroleptic medications, given at recommended dosage and duration based on the clinician's judgment)
- Persistent high level of tic severity for 4 months despite efforts to control the tics using medications, or the presence of self injurious tics
- Duration of the index episode of at least a year
- Individuals who cannot tolerate medications of class and dose at the specified duration as described above will also be included
- Patients currently on medication must be at the same stable dose(s) for one month prior to enrollment and be willing to continue at the same dose(s) through the duration of the study
Who cannot join
- Individuals diagnosed with major depressive disorder (current) of moderate or severe intensity (CGI ≥ 4), bipolar disorder (lifetime), any psychotic disorder (lifetime), or an Axis II personality disorder; with a history of substance abuse or dependence within the past year (except nicotine and caffeine); or at significant acute suicide risk will be excluded
- Other exclusion criteria include those common to every TMS protocol:
- Individuals with a clinically defined neurological disorder, with an increased risk of seizure for any reason, with a history of treatment with TMS, deep brain stimulation for any disorder will be excluded
- Patients with cardiac pacemakers, implanted medication pumps, intracardiac lines, or acute, unstable cardiac disease, with intracranial implants (e.g. aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed will be excluded
- Current use of any investigational drug, any medications with proconvulsive action, such as bupropion, maprotiline, tricyclic antidepressant, clomipramine, classical antipsychotics, and daily use of any medications with a known inhibitory effect on cortical excitability measures (e.g., anticonvulsants, standing doses of benzodiazepines, sedative/hypnotics, and atypical antipsychotics) will not be permitted
- If participating in psychotherapy, patients must have been in stable treatment for at least three months prior to entry into the study, with no anticipation of change in frequency therapeutic sessions, or the therapeutic focus over the duration of the TMS trial
- Finally, current significant laboratory abnormality, known or suspected pregnancy, women who are breast-feeding or women of childbearing potential not using a medically accepted form of contraception when engaging in sexual intercourse will also be excluded.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Yale University School of Medicine
New Haven, Connecticut, 06520
New York State Psychiatric Institute
New York, New York, 10032
About this study
Official title: Transcranial Magnetic Stimulation for Individuals With Tourette's Syndrome
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:
- Compared to sham (placebo), active rTMS will improve symptoms of TS as assessed with the Yale Global Tic Severity Scale (Y-GTSS) and Clinical Global Impression (CGI).
- Active (but not sham) rTMS will normalize levels of motor cortex excitability, as reflected by increased intracortical inhibition, motor threshold, and cortical silent period, and by decreased intracortical facilitation, relative to pre-treatment baseline.
Read the detailed description
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.
- Conditions
- Tourette Syndrome
- Being tested
- Transcranial Magnetic Stimulation (active), Transcranial Magnetic Stimulation (sham)
- Keywords
- Tourette, Tourette's
- Medical subject headings
- Tourette Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcranial Magnetic Stimulation (active)Device
Also called Magstim Rapid2
Magstim Rapid2 stimulator with Air Film Coil at 110% motor threshold at 1Hz for 30 minutes.
Transcranial Magnetic Stimulation (sham)Device
Also called Magstim Rapid2
Magstim Rapid2 stimulator with Sham Air Film Coil at 110% motor threshold at 1Hz for 30 minutes.
| Study group | Role | What they receive |
|---|---|---|
| Active | Active comparator | Not described Receives: Device: Transcranial Magnetic Stimulation (active) |
| Sham | Sham comparator | Not described Receives: Device: Transcranial Magnetic Stimulation (sham) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 3 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2007 (estimated)
- Study startJul 2007
- Primary completionJul 2011
- Study completionJul 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (47)Papers the sponsor has linked to this study.
- Other trials for Tourette SyndromeStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- Tourette Association of America
- Responsible party
- Principal investigator, Angeli Landeros-Weisenberger, Yale University
- Investigators
- Antonio Mantovani, MD, Principal investigator, New York State Psychiatric Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00529308
- Sponsor's protocol ID
- 5480
- Acronym
- TMS
- Status last verified
- Feb 2019
- First submitted
- 13 Sep 2007
- Last updated
- 21 Feb 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Alexander GE, Crutcher MD, DeLong MR. Basal ganglia-thalamocortical circuits: parallel substrates for motor, oculomotor, "prefrontal" and "limbic" functions. Prog Brain Res. 1990;85:119-46.
PubMed 2094891Allison DB, Mentore JL, Heo M, Chandler LP, Cappelleri JC, Infante MC, Weiden PJ. Antipsychotic-induced weight gain: a comprehensive research synthesis. Am J Psychiatry. 1999 Nov;156(11):1686-96. doi: 10.1176/ajp.156.11.1686.
PubMed 10553730Artola A, Brocher S, Singer W. Different voltage-dependent thresholds for inducing long-term depression and long-term potentiation in slices of rat visual cortex. Nature. 1990 Sep 6;347(6288):69-72. doi: 10.1038/347069a0.
PubMed 1975639Bliss TV, Gardner-Medwin AR. Long-lasting potentiation of synaptic transmission in the dentate area of the unanaestetized rabbit following stimulation of the perforant path. J Physiol. 1973 Jul;232(2):357-74. doi: 10.1113/jphysiol.1973.sp010274.
PubMed 4727085Bruggeman R, van der Linden C, Buitelaar JK, Gericke GS, Hawkridge SM, Temlett JA. Risperidone versus pimozide in Tourette's disorder: a comparative double-blind parallel-group study. J Clin Psychiatry. 2001 Jan;62(1):50-6. doi: 10.4088/jcp.v62n0111.
PubMed 11235929Chen R, Classen J, Gerloff C, Celnik P, Wassermann EM, Hallett M, Cohen LG. Depression of motor cortex excitability by low-frequency transcranial magnetic stimulation. Neurology. 1997 May;48(5):1398-403. doi: 10.1212/wnl.48.5.1398.
PubMed 9153480Elwood RW. The California Verbal Learning Test: psychometric characteristics and clinical application. Neuropsychol Rev. 1995 Sep;5(3):173-201. doi: 10.1007/BF02214761.
PubMed 8653108Greenberg BD, Ziemann U, Cora-Locatelli G, Harmon A, Murphy DL, Keel JC, Wassermann EM. Altered cortical excitability in obsessive-compulsive disorder. Neurology. 2000 Jan 11;54(1):142-7. doi: 10.1212/wnl.54.1.142.
PubMed 10636140Hoffman RE, Cavus I. Slow transcranial magnetic stimulation, long-term depotentiation, and brain hyperexcitability disorders. Am J Psychiatry. 2002 Jul;159(7):1093-102. doi: 10.1176/appi.ajp.159.7.1093.
PubMed 12091184Kirkwood A, Dudek SM, Gold JT, Aizenman CD, Bear MF. Common forms of synaptic plasticity in the hippocampus and neocortex in vitro. Science. 1993 Jun 4;260(5113):1518-21. doi: 10.1126/science.8502997.
PubMed 8502997Leckman JF. Tourette's syndrome. Lancet. 2002 Nov 16;360(9345):1577-86. doi: 10.1016/S0140-6736(02)11526-1.
PubMed 12443611Leckman JF, Hardin MT, Riddle MA, Stevenson J, Ort SI, Cohen DJ. Clonidine treatment of Gilles de la Tourette's syndrome. Arch Gen Psychiatry. 1991 Apr;48(4):324-8. doi: 10.1001/archpsyc.1991.01810280040006.
PubMed 2009034Leckman JF, Vaccarino FM, Kalanithi PS, Rothenberger A. Annotation: Tourette syndrome: a relentless drumbeat--driven by misguided brain oscillations. J Child Psychol Psychiatry. 2006 Jun;47(6):537-50. doi: 10.1111/j.1469-7610.2006.01620.x.
PubMed 16712630Marsh R, Alexander GM, Packard MG, Zhu H, Wingard JC, Quackenbush G, Peterson BS. Habit learning in Tourette syndrome: a translational neuroscience approach to a developmental psychopathology. Arch Gen Psychiatry. 2004 Dec;61(12):1259-68. doi: 10.1001/archpsyc.61.12.1259.
PubMed 15583117Moll GH, Heinrich H, Gevensleben H, Rothenberger A. Tic distribution and inhibitory processes in the sensorimotor circuit during adolescence: a cross-sectional TMS study. Neurosci Lett. 2006 Jul 31;403(1-2):96-9. doi: 10.1016/j.neulet.2006.04.021. Epub 2006 May 9.
PubMed 16690208
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Transcranial Magnetic Stimulation for Individuals With Tourette's Syndrome
- ClinicalTrials.gov ID
- NCT00529308
- Acronym / sponsor ID
- TMS / 5480
- Conditions
- Tourette Syndrome
- Keywords
- Tourette, Tourette's
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- Tourette Association of America
- Study start
- Jul 2007
- Primary completion
- Jul 2011 (actual)
- Study completion
- Jul 2011 (actual)
- First posted
- 14 Sep 2007 (estimated)
- Results
- Posted 15 Feb 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Compared to sham (placebo), active rTMS will improve symptoms of TS as assessed with the Yale Global Tic Severity Scale (Y-GTSS) and Clinical Global Impression (CGI).
- Active (but not sham) rTMS will normalize levels of motor cortex excitability, as reflected by increased intracortical inhibition, motor threshold, and cortical silent period, and by decreased intracortical facilitation, relative to pre-treatment baseline.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active | Active comparator | Device: Transcranial Magnetic Stimulation (active) |
| Sham | Sham comparator | Device: Transcranial Magnetic Stimulation (sham) |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Primary diagnosis of Tourette's Syndrome, as confirmed by the DSM-IV-TR criteria
- Residual TS symptoms, defined as a total Y-GTSS total motor tic or phonic tic score > 20, despite treatment with an adequate trial of medications (defined as a failure to respond to a trial of commonly used medications for TS such as clonidine, guanfacine, or neuroleptic medications, given at recommended dosage and duration based on the clinician's judgment)
- Persistent high level of tic severity for 4 months despite efforts to control the tics using medications, or the presence of self injurious tics
- Duration of the index episode of at least a year
- Individuals who cannot tolerate medications of class and dose at the specified duration as described above will also be included
Key exclusion criteria (7 listed)
- Individuals diagnosed with major depressive disorder (current) of moderate or severe intensity (CGI ≥ 4), bipolar disorder (lifetime), any psychotic disorder (lifetime), or an Axis II personality disorder; with a history of substance abuse or dependence within the past year (except nicotine and caffeine); or at significant acute suicide risk will be excluded
- Individuals with a clinically defined neurological disorder, with an increased risk of seizure for any reason, with a history of treatment with TMS, deep brain stimulation for any disorder will be excluded
- Patients with cardiac pacemakers, implanted medication pumps, intracardiac lines, or acute, unstable cardiac disease, with intracranial implants (e.g. aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed will be excluded
- Current use of any investigational drug, any medications with proconvulsive action, such as bupropion, maprotiline, tricyclic antidepressant, clomipramine, classical antipsychotics, and daily use of any medications with a known inhibitory effect on cortical excitability measures (e.g., anticonvulsants, standing doses of benzodiazepines, sedative/hypnotics, and atypical antipsychotics) will not be permitted
- If participating in psychotherapy, patients must have been in stable treatment for at least three months prior to entry into the study, with no anticipation of change in frequency therapeutic sessions, or the therapeutic focus over the duration of the TMS trial
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transcranial Magnetic Stimulation (active)Also: Magstim Rapid2Magstim Rapid2 stimulator with Air Film Coil at 110% motor threshold at 1Hz for 30 minutes. | Device | Active |
| Transcranial Magnetic Stimulation (sham)Also: Magstim Rapid2Magstim Rapid2 stimulator with Sham Air Film Coil at 110% motor threshold at 1Hz for 30 minutes. | Device | Sham |
Primary outcome
Yale Global Tic Severity Scale (Y-GTSS)
Time frame: 3 weeks
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.
Motor Cortex Excitability Normalization-Right Motor Threshold
Time frame: 3 weeks
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.
Number of Patients With "Much Improved or Very Much Improved" on Clinical Global Impression-Improvement (CGI) Scale
Time frame: 3 weeks
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.
Motor Cortex Excitability Normalization-Left Motor Threshold
Time frame: 3 weeks
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.
Number of Patients With "Improved or Minimally Improved" in Clinical Global Impression-Improvement (CGI) Scale
Time frame: 3 weeks
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 2094891Alexander GE, Crutcher MD, DeLong MR. Basal ganglia-thalamocortical circuits: parallel substrates for motor, oculomotor, "prefrontal" and "limbic" functions. Prog Brain Res. 1990;85:119-46.
- Background: PubMed 10553730Allison DB, Mentore JL, Heo M, Chandler LP, Cappelleri JC, Infante MC, Weiden PJ. Antipsychotic-induced weight gain: a comprehensive research synthesis. Am J Psychiatry. 1999 Nov;156(11):1686-96. doi: 10.1176/ajp.156.11.1686.
- Background: PubMed 1975639Artola A, Brocher S, Singer W. Different voltage-dependent thresholds for inducing long-term depression and long-term potentiation in slices of rat visual cortex. Nature. 1990 Sep 6;347(6288):69-72. doi: 10.1038/347069a0.
- Background: PubMed 4727085Bliss TV, Gardner-Medwin AR. Long-lasting potentiation of synaptic transmission in the dentate area of the unanaestetized rabbit following stimulation of the perforant path. J Physiol. 1973 Jul;232(2):357-74. doi: 10.1113/jphysiol.1973.sp010274.
- Background: PubMed 11235929Bruggeman R, van der Linden C, Buitelaar JK, Gericke GS, Hawkridge SM, Temlett JA. Risperidone versus pimozide in Tourette's disorder: a comparative double-blind parallel-group study. J Clin Psychiatry. 2001 Jan;62(1):50-6. doi: 10.4088/jcp.v62n0111.
- Background: PubMed 9153480Chen R, Classen J, Gerloff C, Celnik P, Wassermann EM, Hallett M, Cohen LG. Depression of motor cortex excitability by low-frequency transcranial magnetic stimulation. Neurology. 1997 May;48(5):1398-403. doi: 10.1212/wnl.48.5.1398.
- Background: PubMed 8653108Elwood RW. The California Verbal Learning Test: psychometric characteristics and clinical application. Neuropsychol Rev. 1995 Sep;5(3):173-201. doi: 10.1007/BF02214761.
- Background: PubMed 10636140Greenberg BD, Ziemann U, Cora-Locatelli G, Harmon A, Murphy DL, Keel JC, Wassermann EM. Altered cortical excitability in obsessive-compulsive disorder. Neurology. 2000 Jan 11;54(1):142-7. doi: 10.1212/wnl.54.1.142.
- Background: PubMed 12091184Hoffman RE, Cavus I. Slow transcranial magnetic stimulation, long-term depotentiation, and brain hyperexcitability disorders. Am J Psychiatry. 2002 Jul;159(7):1093-102. doi: 10.1176/appi.ajp.159.7.1093.
- Background: PubMed 8502997Kirkwood A, Dudek SM, Gold JT, Aizenman CD, Bear MF. Common forms of synaptic plasticity in the hippocampus and neocortex in vitro. Science. 1993 Jun 4;260(5113):1518-21. doi: 10.1126/science.8502997.
- Background: PubMed 12443611Leckman JF. Tourette's syndrome. Lancet. 2002 Nov 16;360(9345):1577-86. doi: 10.1016/S0140-6736(02)11526-1.
- Background: PubMed 2009034Leckman JF, Hardin MT, Riddle MA, Stevenson J, Ort SI, Cohen DJ. Clonidine treatment of Gilles de la Tourette's syndrome. Arch Gen Psychiatry. 1991 Apr;48(4):324-8. doi: 10.1001/archpsyc.1991.01810280040006.
- Study summary on Brain Stimulation Division web siteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Antonio Mantovani, MD principal investigator
New York State Psychiatric Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Transcranial Magnetic Stimulation (active) in people with Tourette Syndrome, run by Yale University at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Feb 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Yale Global Tic Severity Scale (Y-GTSS) (time frame: 3 weeks). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00529308, which also lists 47 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Feb 2019.