Theta Burst Stimulation for Tourette Syndrome

Overseen By Donald L Gilbert, MD MS

Age: < 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: Children's Hospital Medical Center, Cincinnati

Disqualifiers: Neurodevelopmental, Psychiatric, Metallic devices, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 2 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to reduce tics in individuals with Tourette Syndrome using Intermittent Theta Burst Stimulation (iTBS), a type of non-invasive brain stimulation. The goal is to enhance control over movement-related brain areas, potentially reducing tics. Participants will receive both real and sham (placebo) treatments to compare effects. This trial may suit individuals aged 10-21 diagnosed with Tourette Syndrome who have stable symptoms without recent medication changes. As an Early Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to experience this innovative approach.

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

The trial protocol does not specify if you need to stop your current medications. However, you must not have changed your psychotropic medications or increased their dosage in the last 14 days before starting the TMS treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must not have changed your psychotropic medications or increased their dosage in the 14 days before starting the treatment.

What prior data suggests that this iTBS technique is safe for Tourette Syndrome patients?

Research shows that intermittent theta burst stimulation (iTBS) is generally safe and well-tolerated. The FDA has approved iTBS for treating depression, indicating a good safety record for that condition. A review found that iTBS is well-tolerated when used on the front part of the brain. Another study found that a single session of theta burst stimulation is safe for children and does not cause significant side effects.

Although specific safety data for using iTBS in Tourette Syndrome is not yet available, its approval for another condition and its non-invasive nature are encouraging. This trial is in an early phase, focusing primarily on safety before assessing the treatment's effectiveness. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Tourette Syndrome?

Researchers are excited about iTBS (intermittent Theta Burst Stimulation) for Tourette Syndrome because it offers a non-invasive approach that targets brain activity in a novel way. Unlike standard treatments, which often involve medications like antipsychotics or behavioral therapies, iTBS uses magnetic pulses to potentially modify brain circuits associated with tics. This method could lead to fewer side effects compared to traditional drug therapies, and the potential for rapid symptom relief makes it a promising option for patients who have not responded well to existing treatments.

What evidence suggests that iTBS might be an effective treatment for Tourette Syndrome?

Research suggests that Intermittent Theta Burst Stimulation (iTBS) may improve movement and mood in various conditions. This treatment uses repetitive transcranial magnetic stimulation (rTMS) to adjust brain activity. Studies have shown that brain stimulation can help with symptoms of Tourette Syndrome (TS), although results have been mixed. In this trial, participants will receive either active iTBS or sham iTBS to evaluate its effectiveness in reducing tics by targeting specific brain areas. While more research is needed specifically for Tourette's, early findings indicate that iTBS is a safe and practical option. ^{3 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for young people aged 10-21 with Tourette Syndrome (TS) who speak English and can understand the study. They should be clinically stable, meaning no recent changes in their psychotropic medications or other therapies. Participants must not have any metal in their body or certain psychiatric conditions beyond TS, ADHD, OCD, or mild anxiety.

Inclusion Criteria

My mental health treatment has been stable for the last 14 days.

I am between 10 and 21 years old.

Fluent in English

Exclusion Criteria

Presence of metallic foreign bodies or implanted medical devices

Not meeting inclusion criteria as described above

Any neurodevelopmental, psychiatric condition other than TS, ADHD, or OCD, or mild anxiety based on review of K-SADS

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive active or sham pre-SMA iTBS on two separate study days, with a minimum of 5 days between sessions

2 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• iTBS

Trial Overview The trial tests a non-invasive brain stimulation technique called intermittent theta-burst repetitive TMS (iTBS). It's designed to improve motor control by targeting a specific part of the brain involved in movement regulation. The study compares real iTBS treatment to a sham (fake) procedure to see if it can reduce tics in TS patients.

How Is the Trial Designed?

Group I: iTBS Experimental Treatment 1 Intervention

Each participant will have two separate study days in the TMS lab. On one day, the participant will receive active pre-SMA iTBS. On the other day, the patricipant will receive sham pre-SMA iTBS. The order that active versus sham is given will be randomized and the participant will be blinded. After each iTBS session, blinding assessment will be performed. To avoid contamination of results, a minimum of 5 days between study days will be required.

Group II: Sham iTBS Placebo Group 1 Intervention

Each participant will have two separate study days in the TMS lab. On one day, the participant will receive active pre-SMA iTBS. On the other day, the patricipant will receive sham pre-SMA iTBS. The order that active versus sham is given will be randomized and the participant will be blinded. After each iTBS session, blinding assessment will be performed. To avoid contamination of results, a minimum of 5 days between study days will be required.

iTBS is already approved in United States for the following indications:

Approved in United States as iTBS for:

• Treatment-resistant depression
• Major depressive disorder

Who Is Running the Clinical Trial?

Children's Hospital Medical Center, Cincinnati

Lead Sponsor

Trials

844

Recruited

6,566,000+

Tourette Association of America

Collaborator

Trials

12

Recruited

500+

Published Research Related to This Trial

In a 10-week study involving 11 children and adolescents with Tourette's disorder, aripiprazole significantly reduced tic severity, with most participants showing marked improvement in their symptoms.

The treatment was generally safe and well-tolerated, although some participants experienced side effects like increased appetite, weight gain, and mild extrapyramidal symptoms, indicating the need for further controlled trials to confirm its efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aripiprazole in children and adolescents with Tourette's disorder: an open-label safety and tolerability study. Lyon, GJ., Samar, S., Jummani, R., et al.[2021]

Deep brain stimulation (DBS) significantly reduces Tourette syndrome (TS) symptoms more effectively than pharmacotherapy or psychotherapy, with a reduction of 49.9% in YGTSS scores compared to 22.5% and 20.0% for medications and therapy, respectively.

DBS has a low complication rate of 0.15 adverse effects per case, indicating it is a safe option for adults with refractory TS compared to higher rates associated with pharmacotherapy (1.13/case) and psychotherapy (0.60/case).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep Brain Stimulation Results in Greater Symptomatic Improvement in Tourette Syndrome than Conservative Measures: A Meta-Analysis. Mahajan, UV., Purger, DA., Mantovani, A., et al.[2021]

In a study involving 36 multiple sclerosis patients, intermittent theta burst stimulation (iTBS) significantly improved manual dexterity, as shown by faster completion times in the nine-hole peg test and increased performance in the Box and Block Test.

However, iTBS did not have a significant impact on hand motor imagery abilities, indicating that while it can enhance physical tasks, it may not affect cognitive aspects of motor function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Intermittent Theta Burst Stimulation on Manual Dexterity and Motor Imagery in Patients with Multiple Sclerosis: A Quasi-Experimental Controlled Study. Azin, M., Zangiabadi, N., Iranmanesh, F., et al.[2020]

Intermittent theta-burst stimulation (iTBS) significantly improves hand function in stroke patients, particularly in those with higher baseline motor function and the presence of motor-evoked potentials (MEPs).

The study of 72 stroke patients showed that those with MEPs and better grip strength (Group A) had the greatest improvement in motor function, suggesting that iTBS effectiveness can be predicted by these factors, allowing for more tailored neurostimulation strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Corticospinal integrity and motor impairment predict outcomes after excitatory repetitive transcranial magnetic stimulation: a preliminary study. Lai, CJ., Wang, CP., Tsai, PY., et al.[2016]

In a study involving 208 participants with treatment-resistant depression, both twice-daily and once-daily intermittent theta burst stimulation (iTBS) protocols showed improvements in depression scores, but there was no significant difference in efficacy between the two schedules after 10 and 30 days.

Response and remission rates were low in both treatment groups, indicating that neither protocol significantly accelerated the improvement of depressive symptoms in patients with treatment-resistant depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized sham controlled comparison of once vs twice-daily intermittent theta burst stimulation in depression: A Canadian rTMS treatment and biomarker network in depression (CARTBIND) study. Blumberger, DM., Vila-Rodriguez, F., Wang, W., et al.[2022]

In a study involving 40 patients with chronic tinnitus, both the active treatment group and the placebo control group showed significant improvements in tinnitus functional index (TFI) scores after treatment, indicating a strong placebo effect.

However, there was no significant difference in TFI score improvements between the active treatment and sham groups, suggesting that theta burst repetitive transcranial magnetic stimulation may not be an effective therapeutic option for chronic tinnitus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Tinnitus Using Theta Burst Based Repetitive Transcranial Magnetic Stimulation-A Single Blinded Randomized Control Trial. Godbehere, J., Sandhu, J., Evans, A., et al.[2020]

In a study involving 20 patients with chronic tinnitus, theta-burst stimulation (TBS) applied to the inferior temporal cortex was found to be safe, but did not show significant overall effectiveness in reducing tinnitus perception compared to different TBS types.

While some patients experienced slight improvements, only continuous TBS (cTBS) resulted in a significant short-term reduction in symptoms, indicating that TBS may not be a promising treatment option for tinnitus based on this study's findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does a single session of theta-burst transcranial magnetic stimulation of inferior temporal cortex affect tinnitus perception? Poreisz, C., Paulus, W., Moser, T., et al.[2021]

The 'activate & fire' treatment combining acoustic stimulation with continuous theta burst stimulation (cTBS) was well tolerated by most tinnitus patients, suggesting it could be a promising approach for treatment.

However, the study did not find statistical superiority of this new method over traditional low-frequency rTMS in alleviating tinnitus symptoms, indicating that further research with larger sample sizes is needed to confirm its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activate & fire: a feasibility study in combining acoustic stimulation and continuous theta burst stimulation in chronic tinnitus. Schoisswohl, S., Langguth, B., Weber, FC., et al.[2023]

Valbenazine, a VMAT2 inhibitor, showed a trend towards reducing tics in Tourette syndrome patients compared to placebo, but this difference was not statistically significant across six trials involving both adult and pediatric subjects.

The medication was generally well-tolerated, with side effects consistent with its use in treating tardive dyskinesia, but due to not meeting the primary efficacy endpoint, further development of valbenazine for Tourette syndrome is unlikely.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical development of valbenazine for tics associated with Tourette syndrome. Farber, RH., Angelov, A., Kim, K., et al.[2022]

Intermittent theta-burst stimulation (iTBS) is safe for patients with mild to moderate Parkinson's disease, showing no significant increase in cortical excitability or adverse effects during the treatment.

While iTBS improved mood in patients, it did not lead to any significant improvements in motor symptoms such as gait or bradykinesia, based on a study of 26 participants over 2 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent theta-burst transcranial magnetic stimulation for treatment of Parkinson disease. Benninger, DH., Berman, BD., Houdayer, E., et al.[2021]

Transcranial magnetic theta burst stimulation (TBS) effectively reduced tinnitus intensity in a 54-year-old woman, with scores decreasing from 84 to 59 points after three cycles of treatment.

TBS also significantly alleviated symptoms of severe depression, as indicated by a drop in the Hamilton Rating Scale for Depression score from 44 to 23 points, demonstrating its potential as a practical and well-tolerated intervention for patients with tinnitus and depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Theta burst stimulation in the treatment of incapacitating tinnitus accompanied by severe depression. Soekadar, SR., Arfeller, C., Rilk, A., et al.[2019]

The study involved 15 patients with tinnitus who underwent multiple daily rounds of continuous theta burst stimulation (cTBS) over five days, and the treatment was completed without any adverse events, indicating safety.

Despite the safety of the treatment, the study did not find significant therapeutic effects on tinnitus symptoms, suggesting that more research with a larger sample size is necessary to evaluate the effectiveness of cTBS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiple Daily Rounds of Theta-Burst Stimulation for Tinnitus: Preliminary Results. Hong, SM., Kim, SK., Seo, MY., et al.[2021]

Deep brain stimulation (DBS) has shown promising efficacy in improving tics and some comorbidities in treatment-resistant patients with Tourette syndrome, based on 34 studies involving over 90 patients.

The safety profile of DBS indicates that serious adverse events are rare and typically do not lead to significant impairment, but more randomized controlled trials are needed to draw definitive conclusions about its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgical treatment of Tourette syndrome. Müller-Vahl, KR.[2013]

Thalamic deep brain stimulation (DBS) showed significant long-term tic reduction in some patients with Tourette syndrome, with one patient experiencing an 88.9% improvement over 78 months, indicating potential for sustained efficacy.

However, the long-term follow-up revealed increasing side effects, such as reduced energy and visual disturbances, leading some patients to switch off the stimulator or require additional surgeries to change the stimulation target.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thalamic Deep Brain Stimulation for Refractory Tourette Syndrome: Clinical Evidence for Increasing Disbalance of Therapeutic Effects and Side Effects at Long-Term Follow-Up. Smeets, AYJM., Duits, AA., Leentjens, AFG., et al.[2022]

Intermittent theta burst stimulation (iTBS) is as effective as standard high-frequency (10 Hz) rTMS for treating treatment-resistant depression, showing non-inferiority in improving depression scores over 4-6 weeks in a study with 414 participants.

Both iTBS and 10 Hz rTMS had similar safety profiles and dropout rates, with headaches being the most common side effect, indicating that iTBS can be a viable alternative that allows for more patients to be treated in a shorter time without losing effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial. Blumberger, DM., Vila-Rodriguez, F., Thorpe, KE., et al.[2022]

Citations

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Altered neurophysiologic response to intermittent theta ... Motor-evoked potential amplitude changes over 1 and 10 minutes after intermittent theta burst transcranial magnetic stimulation were greater in 11 healthy ...

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Non-invasive brain stimulation as therapy In this systematic review, we explore the topic of non-invasive brain stimulation (NIBS) as a potential treatment, or adjunct to treatment, to help people with ...

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Tourette syndrome and brain stimulation therapy Our analysis revealed both DBS and rTMS improved TS and OCD symptoms, however the effect of rTMS on TS in RCTs was insignificant, suggesting DBS stimulation is ...

4. withpower.com withpower.com/trial/early-phase-1-tourette-syndrome-10-2022-e3faa

Theta Burst Stimulation for Tourette Syndrome iTBS, or Intermittent Theta Burst Stimulation, is a promising treatment because it has shown positive effects in improving motor functions and mood in other ...

5. neuromodulationjournal.org neuromodulationjournal.org/article/S1094-7159(21)06424-2/fulltext

A Systematic Review of the Safety and Tolerability of Theta ... TBS interventions in children may have similar safety, tolerability, and feasibility as compared to adults. However, long-term, follow-up studies of TBS are ...

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A Systematic Review of the Safety and Tolerability of Theta ... In 2018 the FDA cleared intermittent theta burst stimulation (iTBS) delivered to the left dorsolateral prefrontal cortex for the treatment of major depressive ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/22515662/

Safety and Tolerability of Theta-Burst Transcranial ... A single session of TBS in children appears to be safe and well tolerated.

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1935861X15008967

Efficacy and Time Course of Theta Burst Stimulation in ... ITBS applied for 190 s significantly increases cortical excitability up to 60 min with a mean maximum potentiation of 35.54 ± 3.32%.