Combined CBIT and rTMS to Improve Tourette's Syndrome
Condition: Tourette Syndrome
MeSH terms: Tourette Syndrome; Syndrome
Study type: Interventional

Summary: 
      The investigator will apply 16 sessions of repetitive transcranial magnetic stimulation
      (rTMS) over 4 consecutive days for adult patients suffering from Tourette's Syndrome.
      Following rTMS, patients will undergo 8 sessions of Comprehensive Behavioral Intervention for
      Tics (CBIT) over 10 weeks via telemedicine. Clinical improvement in tic severity will be the
      primary outcome measure. Secondary outcome measures including underlying physiological
      effects will be measured via functional magnetic resonance imaginge (fMRI), high-density
      electroencephalograhy (HD-EEG), and TMS.
    

Detailed description: 
      Patients will be randomly assigned to active or sham stimulation, with 10 in each group,
      followed by 10 weeks of tele-CBIT. Patients will have primary and secondary outcome measures
      performed at four time points: Baseline (T0), following rTMS (T1), following CBIT (T2), and 1
      month later (T3). The rTMS protocol will consist of 6 trains targeted to the supplementary
      motor area (SMA) lasting 5 minutes each (300 pulses per train) with an intertrain interval of
      1 minute for a total duration of 35 minutes (1800 pulses). Patients will receive 4 sessions
      each day on 4 consecutive days for a total of 16 sessions. Daily duration of this study
      protocol should last approximately 170 minutes including a 10 minute break in between each
      session. The sham protocol will be the same except a sham coil will be used instead of an
      active coil. Following rTMS, patients will undergo 10 weeks of tele-CBIT.

      The following outcome measures will be collected at four timepoints (T0, T1, T2, and T3):

      Tics will be examined with the standardized Yale Global Tic Severity Scale (YGTSS) and the
      modified Rush Videotape Tic Rating Scale (mRVTRS), and co-morbid symptoms with the Beck
      Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Yale-Brown Obsessive Compulsive
      Scale (Y-BOCS) and Adult ADHD Self-Reports Scale (ASRS). Quality of life will be assessed
      with the Gilles de la Tourette Syndrome - Quality of Life scale (GTS-QOL).

      TMS measures: A single-pulse of TMS will be targeted over the motor cortex to generate a
      motor evoked potential (MEP), which can be captured on EMG. The rest of the EMG will be
      analyzed to assess the time between the TMS pulse and the MEP (also known as the latency) and
      the amount of time muscle activity remains silent following the MEP (also known as the
      cortical silent period). In a paired-pulse TMS paradigm, a subthreshold pulse will be
      provided followed by an interstimulus interval and then subsequent delivery of a
      suprathreshold pulse. When the interstimulus interval is short (1-4 msec), the ratio of MEP
      amplitudes produced by these two pulses is known as short interval intracortical inhibition
      (SICI).

      fMRI measure: Functional MRI will be used to record Blood Oxygen Level Dependent (BOLD)
      activity changes in patients at rest.

      HD-EEG measure: A 128-electrode cap will be used to assess electrical activity in patients at
      rest and actively trying to suppress their tics.
    

Intervention name(s): Transcranial Magnetic Stimulation; Comprehensive behavioral intervention
Intervention type(s): Device; Behavioral
Intervention description(s): rTMS will be delivered using a MagStim Super Rapid2 TMS therapy system.; Patients will receive CBIT with a therapist trained in CBIT. Each session will last about an hour and will be delivered remotely via telemedicine. Sessions will be tailed to the patient's individual needs.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: TMS; Transcranial magnetic stimulation; CBIT; Comprehensive Behavioral Intervention for Tics; Tourette Syndrome