Transcranial Magnetic Stimulation (TMS) for Individuals With Tourette's Syndrome
Condition: Tourette Syndrome
MeSH terms: Tourette Syndrome; Syndrome
Intervention: Transcranial Magnetic Stimulation (active); Transcranial Magnetic Stimulation (sham)
Intervention description: Magstim Rapid2 stimulator with Air Film Coil at 110% motor threshold at 1Hz for 30 minutes.; Magstim Rapid2 stimulator with Sham Air Film Coil at 110% motor threshold at 1Hz for 30 minutes.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Tourette; Tourette's

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. 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.
    

Eligibility criteria:

        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.