Clinical trial NCT03642951: Multi-site Transcranial Magnetic Stimulation Therapy of the Supplementary Motor Area in Children With Tourette Syndrome
Official title: Multi-site Transcranial Magnetic Stimulation Therapy of the Supplementary Motor Area in Children With Tourette Syndrome
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Tourette Syndrome
Keywords: magnetic
brain
stimulation
Lead sponsor: Children's Mercy Hospital Kansas City
Sponsor class: OTHER
Collaborators: name: The Methodist Hospital Research Institute
name: Cornell University
First posted: 2018-08-22
Enrollment: 0
Sex: ALL
Minimum age (years): 8
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The investigators are investigating the effectiveness of a wearable multisite transcranial magnetic stimulation (mTMS) device that can deliver stimuli at multiple cortical sites simultaneously or sequentially for the treatment of Tourette Syndrome.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in tic severity from baseline to 2 months post-treatment
timeFrame: Day of first treatment session, End of weeks 1 and 2, as well as 1 month and 2 months after treatment
Secondary outcomes:
measure: Change in ADHD symptoms from baseline to two months post-treatment
timeFrame: Day of first treatment session, End of weeks 1 and 2, as well as 1 month and 2 months after treatment
measure: Change in OCD symptoms from baseline to two months post-treatment
timeFrame: Day of first treatment session, End of weeks 1 and 2, as well as 1 month and 2 months after treatment
Other outcomes:
Locations:
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
Study officials:
affiliation: Children's Mercy Hospital Kansas City
name: Keith A Coffman, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Robertson MM, Eapen V, Cavanna AE. The international prevalence, epidemiology, and clinical phenomenology of Tourette syndrome: a cross-cultural perspective. J Psychosom Res. 2009 Dec;67(6):475-83. doi: 10.1016/j.jpsychores.2009.07.010.
citation: Termine C, Selvini C, Rossi G, Balottin U. Emerging treatment strategies in Tourette syndrome: what's in the pipeline? Int Rev Neurobiol. 2013;112:445-80. doi: 10.1016/B978-0-12-411546-0.00015-9.
citation: Rossini PM, Rossi S. Transcranial magnetic stimulation: diagnostic, therapeutic, and research potential. Neurology. 2007 Feb 13;68(7):484-8. doi: 10.1212/01.wnl.0000250268.13789.b2.