Transcranial Magnetic Stimulation for Tourette Syndrome

(STOP-TIC Trial)

Overseen By Jessica Frey, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: West Virginia University

Disqualifiers: Metallic objects, Pregnancy, Seizures, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This pilot study will investigate the clinical and neurophysiological effects of repetitive transcranial magnetic stimulation (rTMS) followed by comprehensive behavioral intervention for tics (CBIT) in adult patients with Tourette's Syndrome (TS). Two groups of moderate disease severity will be randomized to receive active or sham rTMS targeted to the supplementary motor area (SMA) followed by eight CBIT sessions. The change in tic frequency and severity (primary outcome) and neurophysiological changes (secondary outcome) will be compared between the two groups. The central hypothesis is that low frequency rTMS will augment the effects of CBIT through favorable priming of the SMA network.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment Transcranial Magnetic Stimulation for Tourette Syndrome?

Some studies suggest that low-frequency repetitive transcranial magnetic stimulation (rTMS) targeting specific brain areas like the supplementary motor area (SMA) might help reduce tic severity in Tourette syndrome, although results are mixed and not consistently significant. ^{1 2 3 4 5}

Is transcranial magnetic stimulation (TMS) safe for humans?

Transcranial magnetic stimulation (TMS), including repetitive TMS (rTMS), has been studied for safety in both healthy individuals and those with various neuropsychiatric conditions. Safety guidelines have been established and updated over the years, indicating that TMS is generally considered safe when proper protocols are followed, though it is important to screen for any individual risks before treatment. ^{1 2 4 6 7}

How is transcranial magnetic stimulation treatment different from other treatments for Tourette syndrome?

Transcranial magnetic stimulation (TMS) is unique because it uses magnetic fields to stimulate specific areas of the brain, unlike traditional treatments that often involve medication. This non-invasive method targets brain regions associated with tics, offering a different approach compared to drugs that affect the whole body. ^{1 2 3 4 8}

Research Team

Jessica Frey, MD

Principal Investigator

WVU RNI

Eligibility Criteria

Adults over 18 with Tourette Syndrome and moderate tic severity can join this study. It's not for those with metal in their brain, pregnant individuals, people with seizures or epilepsy history, anyone who can't have an fMRI, or if another condition prevents them from doing CBIT therapy.

Inclusion Criteria

I am 18 years old or older.

I have been diagnosed with Tourette Syndrome.

Moderate Tic Severity at baseline

Exclusion Criteria

Presence of metallic objects or neurostimulators in the brain

Pregnancy

Contraindications to receiving fMRI

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either active or sham rTMS followed by eight CBIT sessions

8 weeks

Follow-up

Participants are monitored for changes in tic frequency and severity, and neurophysiological changes

4 weeks

Treatment Details

Interventions

• Transcranial Magnetic Stimulation

Trial Overview The trial is testing whether a technique called rTMS enhances the effects of a tic treatment known as CBIT in adults with Tourette's. Participants are randomly assigned to get either real rTMS or a pretend version before starting eight sessions of CBIT.

Participant Groups

Group I: Active rTMS Active Control 1 Intervention

Patients receiving active rTMS

Group II: Sham rTMS Placebo Group 1 Intervention

Patients receiving sham rTMS

Transcranial Magnetic Stimulation is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Transcranial Magnetic Stimulation for:

• Major Depressive Disorder
• Obsessive Compulsive Disorder

Approved in Canada as Transcranial Magnetic Stimulation for:

• Major Depressive Disorder

Approved in European Union as Transcranial Magnetic Stimulation for:

• Major Depressive Disorder

Who Is Running the Clinical Trial?

West Virginia University

Lead Sponsor

Trials

192

Recruited

64,700+

University of Florida

Collaborator

Trials

1,428

Recruited

987,000+

Tourette Association of America

Collaborator

Trials

12

Recruited

500+

Findings from Research

In a phase 1 clinical trial involving 10 children with Tourette syndrome, low-frequency repetitive transcranial magnetic stimulation (rTMS) to the supplementary motor area significantly reduced tic severity, as indicated by a decrease in the Yale Global Tic Severity Scale score (p<0.001).

The rTMS treatment was well-tolerated by all participants, demonstrating that this method is feasible and safe for use in children with Tourette syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bilateral transcranial magnetic stimulation of the supplementary motor area in children with Tourette syndrome. Kahl, CK., Kirton, A., Pringsheim, T., et al.[2021]

In a randomized, blinded, crossover study involving 8 patients with Tourette's syndrome, repetitive transcranial magnetic stimulation (rTMS) was found to be safe, with minimal side effects and no worsening of tics.

Despite the study's design limitations, tic symptoms showed significant improvement over the week, suggesting potential efficacy of rTMS, although further research is needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot safety study of repetitive transcranial magnetic stimulation (rTMS) in Tourette's syndrome. Chae, JH., Nahas, Z., Wassermann, E., et al.[2019]

In a trial involving 16 patients with Gilles de la Tourette syndrome, repetitive transcranial magnetic stimulation (rTMS) did not lead to significant symptom improvement compared to placebo, as assessed by a specific evaluation survey.

The study included a crossover design with three different rTMS conditions (motor, premotor, and sham), but ultimately, the 12 patients who completed the trial showed no notable changes in their tic symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation for Tourette syndrome. Münchau, A., Bloem, BR., Thilo, KV., et al.[2019]

In a study involving five patients with Gilles de la Tourette Syndrome, longer trains of 1Hz rTMS applied to the pre-motor cortex did not significantly reduce tic severity, indicating that this specific protocol may not be effective.

The findings suggest that current rTMS protocols require substantial modifications to potentially benefit patients with tics in GTS, as the tested methods did not yield positive results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subthreshold rTMS over pre-motor cortex has no effect on tics in patients with Gilles de la Tourette syndrome. Orth, M., Kirby, R., Richardson, MP., et al.[2008]

In a randomized double-blind sham-controlled trial involving 20 adults with severe Tourette syndrome, low frequency rTMS targeting the supplementary motor area did not show a statistically significant reduction in tic severity after 3 weeks compared to sham treatment (17.3% vs. 13.2%; P = 0.27).

However, a subsequent open-label treatment phase for those who initially received active rTMS resulted in a significant 29.7% reduction in tic severity compared to baseline (P = 0.04), suggesting that longer or different stimulation protocols may be more effective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Sham Controlled Double-blind Trial of Repetitive Transcranial Magnetic Stimulation for Adults With Severe Tourette Syndrome. Landeros-Weisenberger, A., Mantovani, A., Motlagh, MG., et al.[2018]

Repetitive transcranial magnetic stimulation (rTMS) has gained popularity for its ability to modulate brain activity, but safety considerations are crucial, especially with the recent updates to safety guidelines published in 2021.

The guidelines emphasize the importance of screening for risks, monitoring for adverse events, and specific safety measures when using rTMS, particularly in patients with conditions like stroke and traumatic brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. Kim, WS., Paik, NJ.[2023]

Deep repetitive transcranial magnetic stimulation (rTMS) is safe for treating Tourette syndrome (TS) in adults, with no significant side effects reported in a pilot study involving 12 patients.

While overall tic severity did not improve for the entire group, a notable subgroup of patients with both TS and obsessive-compulsive disorder (OCD) experienced significant reductions in tic severity, suggesting that deep rTMS may be more effective for specific TS presentations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep TMS add-on treatment for intractable Tourette syndrome: A feasibility study. Bloch, Y., Arad, S., Levkovitz, Y.[2018]

Transcranial magnetic stimulation (TMS) has been applied in research on Tourette syndrome (TS) to explore abnormalities in brain pathways that may contribute to tics and co-occurring disorders like ADHD and OCD.

The chapter reviews various TMS techniques, including single- and paired-pulse methods and theta-burst stimulation, highlighting their potential to enhance our understanding of TS and suggesting future research directions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tourette syndrome. Shahana, N., Gilbert, DL.[2013]

References

1. England pubmed.ncbi.nlm.nih.gov

Bilateral transcranial magnetic stimulation of the supplementary motor area in children with Tourette syndrome. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

A pilot safety study of repetitive transcranial magnetic stimulation (rTMS) in Tourette's syndrome. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation for Tourette syndrome. [2019]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Subthreshold rTMS over pre-motor cortex has no effect on tics in patients with Gilles de la Tourette syndrome. [2008]

5. United States pubmed.ncbi.nlm.nih.gov

Randomized Sham Controlled Double-blind Trial of Repetitive Transcranial Magnetic Stimulation for Adults With Severe Tourette Syndrome. [2018]

6. Korea (South) pubmed.ncbi.nlm.nih.gov

Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Deep TMS add-on treatment for intractable Tourette syndrome: A feasibility study. [2018]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Tourette syndrome. [2013]