Transcranial Magnetic Stimulation (TMS) for Individuals With Tourette's Syndrome
Condition: Tourette Syndrome
MeSH terms: Tourette Syndrome; Syndrome
Study type: Interventional
Phase: Phase 2

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.
    

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.
    

Intervention name(s): Transcranial Magnetic Stimulation (active); Transcranial Magnetic Stimulation (sham)
Intervention type(s): Device; Device
Intervention description(s): 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.
Other intervention name(s): Magstim Rapid2; Magstim Rapid2
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Tourette; Tourette's