Multi-site Transcranial Magnetic Stimulation Therapy of the Supplementary Motor Area in Children With Tourette Syndrome

STUDY OBJECTIVES/HYPOTHESIS

Tourette Syndrome (TS) is a neurodevelopmental condition that affects nearly 1% of children
world-wide. While it can be treated with drugs and behavioral therapy, other modalities are
being sought, especially, in cases that are resistant to standard treatment. One such
approach that is being tested in pilot clinical studies is repetitive transcranial magnetic
stimulation (rTMS). Noninvasive magnetic stimulation of the cerebral cortex is an important
and useful technique in neuroscience research, as well as in diagnostic and therapeutic
clinical investigations. Over the last three decades the magnetic stimulation procedure is
being carried out using a device called transcranial magnetic stimulator (TMS), which uses a
large hand-held electromagnetic coil passing high amplitude current to induce a rapidly
changing magnetic field at a single cortical site. TMS has found clinical application in
several neurological and psychiatric conditions such as stroke, major depression, migraine,
movement disorders and Tourette syndrome. One limitation of conventional TMS, besides the
bulkiness of the device and the large amount of current involved, is that it allows
stimulation at only one cortical site at a time. Dr. Santosh Helekar of Houston Methodist
Research Institute (HMRI) and Dr. Henning Voss of Weill-Cornell Medical College (WCMC) have
developed a compact portable and wearable multisite transcranial magnetic stimulation (mTMS)
device that can deliver stimuli at multiple cortical sites simultaneously or sequentially. It
uses rapidly rotating small high strength permanent magnets to induce currents in the brain.
As opposed to conventional TMS, the mTMS device is also ideally suited to conduct
double-blind placebo-controlled studies because undetectable demagnetized magnets can be
intermixed with actual magnets to allow rapid rotation of either type of magnets to be
activated in one and the same device in a randomized protocol. Under a previously approved
HMRI study protocol this new device has been shown to induce motor-evoked potentials (MEPs)
in thenar muscles by highly focused stimulation of their cortical representation in the
precentral gyrus.

In the present pilot study, the investigators would like to conduct a randomized double-blind
placebo-controlled clinical trial to test the therapeutic effectiveness of bilateral mTMS
stimulation of the supplementary motor areas (mTMS-SMA therapy) in TS patients presenting
with tics uncontrolled by standard drug and behavioral treatment. The specifics aims of this
study are:

1. To compare the immediate benefits obtained by TS patients subjected to two weeks of five
day per week mTMS-SMA therapy with respect to those obtained by TS patients receiving
placebo (sham stimulation) treatment, in terms of reduction of the frequency of tics and
alleviation (primary end points) and of other comorbidities (ADHD and OCD, secondary end
points) of TS.

2. To compare the long-term benefits as above over a two-month follow up period in the same
set of treated and placebo control TS patients

The investigators will conduct this study in 20, English speaking, TS patients in the age
range of 8 to 20 years. Half the patients will be randomly assigned in a double-blind manner
to the active treatment or the placebo control (sham treatment) groups that will be
appropriately age-and gender-matched. Randomization will be completed by the study team by
alternating between cap A and cap B, within specific cohorts. The cohorts will be as follows:
8-13 years of age at time of enrollment and 14-20 years of age at time of enrollment. The
stimulus parameters used will be those that are effective in upregulating the excitability of
the motor pathways to elicit MEPs in the thenar muscles. The investigators believe that
mTMS-SMA therapy will produce both short- and long-term benefit for TS patients.

Inclusion Criteria:

- Patients between the ages of 8 and 20 years old,

- A clinical diagnosis of TS as defined by the DSM V

- YGTSS score of 13 or more (performed at Visit 1).

- Patients with the following comorbidities: OCD, ADHD and anxiety disorders (as defined
by the DSM V) will be allowed in the study. This will be assessed during Visit 1.

- The patients may be on medications for the treatment of TS or allowed comorbidities
provided the medication regimen is stable for six weeks prior to inclusion in the
study and remains unchanged for the 10 weeks that the study will last.

Exclusion Criteria:

- Any history of neurological, or psychiatric disorders including epilepsy and autism
spectrum disorder, other than other than the allowed comorbidities (see above).

- An IQ less than 80, this will be assessed during Visit 1.

- Any changes in medications prescribed for the treatment of TS or allowed comorbidities
six weeks prior to inclusion in the study or at any time during the study.

- The presence of metal implants or metallic devices in the head

- Any history of drug or alcohol abuse

- Any medication changes during the six weeks preceding enrollment or at any time during
the 10-week course of the study