Transcranial Magnetic Stimulation (TMS) for Individuals With Tourette's Syndrome (TMS)

February 4, 2019 updated by: Angeli Landeros-Weisenberger, Yale University

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:

  1. 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).
  2. 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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

20

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Connecticut
      • New Haven, Connecticut, United States, 06520
        • Yale University School of Medicine
    • New York
      • New York, New York, United States, 10032
        • New York State Psychiatric Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Active
Device: Transcranial Magnetic Stimulation (active)
Magstim Rapid2 stimulator with Air Film Coil at 110% motor threshold at 1Hz for 30 minutes.
Other Names:
  • Magstim Rapid2
Sham Comparator: Sham
Device: Transcranial Magnetic Stimulation (sham)
Magstim Rapid2 stimulator with Sham Air Film Coil at 110% motor threshold at 1Hz for 30 minutes.
Other Names:
  • Magstim Rapid2

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
3 weeks
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.
3 weeks
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.
3 weeks
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.
3 weeks
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.
3 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Yale University

Collaborators

Tourette Association of America

Investigators

  • Principal Investigator: Antonio Mantovani, MD, New York State Psychiatric Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2007

Primary Completion (Actual)

July 1, 2011

Study Completion (Actual)

July 1, 2011

Study Registration Dates

First Submitted

September 13, 2007

First Submitted That Met QC Criteria

September 13, 2007

First Posted (Estimate)

September 14, 2007

Study Record Updates

Last Update Posted (Actual)

February 21, 2019

Last Update Submitted That Met QC Criteria

February 4, 2019

Last Verified

February 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 5480

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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