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

Trial Summary

What is the purpose of this trial?

This trial uses a non-invasive magnetic pulse therapy to help Tourette Syndrome patients by improving their brain's ability to control movements and reduce tics. This therapy has shown promising results in reducing tic severity in Tourette Syndrome.

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 data supports the idea that Theta Burst Stimulation for Tourette Syndrome is an effective treatment?

The available research shows that Theta Burst Stimulation (TBS) has been used to treat conditions like tinnitus, which is a persistent ringing in the ears, often linked with depression. In one case, a woman's tinnitus intensity decreased significantly after TBS treatment, and her depression symptoms also improved. However, the research does not provide specific data on TBS for Tourette Syndrome. Therefore, while TBS shows promise for other conditions, more research is needed to confirm its effectiveness for Tourette Syndrome. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment iTBS for Tourette Syndrome?

While there is no direct evidence for iTBS in treating Tourette Syndrome, studies have shown that theta burst stimulation (TBS) can help reduce symptoms in conditions like tinnitus and depression by modulating brain activity. This suggests that iTBS might have potential benefits for other neurological conditions, including Tourette Syndrome. ^{1 2 3 4 5}

What safety data exists for Theta Burst Stimulation in treating Tourette Syndrome?

The provided research does not contain specific safety data for Theta Burst Stimulation (iTBS) in treating Tourette Syndrome. The studies focus on other treatments like Deep Brain Stimulation (DBS) and medications such as valbenazine and aripiprazole. To find safety data for iTBS, further research specifically targeting this treatment would be necessary. ^{6 7 8 9 10}

Is iTBS a promising treatment 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 conditions like Parkinson's disease, multiple sclerosis, and depression. It is a newer form of therapy that can be delivered quickly and has been effective in helping patients with treatment-resistant depression. ^{11 12 13 14 15}

How is the treatment iTBS different from other treatments for Tourette Syndrome?

iTBS is a unique treatment because it uses magnetic pulses to stimulate specific areas of the brain, which can be done in just a few minutes per session. This is different from many other treatments that might involve medications or longer therapy sessions. ^{11 12 13 14 15}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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) 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]

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]

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]

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]

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]

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]

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]

References

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

Theta burst stimulation in the treatment of incapacitating tinnitus accompanied by severe depression. [2019]

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

Treatment of Tinnitus Using Theta Burst Based Repetitive Transcranial Magnetic Stimulation-A Single Blinded Randomized Control Trial. [2020]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Multiple Daily Rounds of Theta-Burst Stimulation for Tinnitus: Preliminary Results. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Does a single session of theta-burst transcranial magnetic stimulation of inferior temporal cortex affect tinnitus perception? [2021]

5. England pubmed.ncbi.nlm.nih.gov

Activate & fire: a feasibility study in combining acoustic stimulation and continuous theta burst stimulation in chronic tinnitus. [2023]

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

Aripiprazole in children and adolescents with Tourette's disorder: an open-label safety and tolerability study. [2021]

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

Surgical treatment of Tourette syndrome. [2013]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Deep Brain Stimulation Results in Greater Symptomatic Improvement in Tourette Syndrome than Conservative Measures: A Meta-Analysis. [2021]

9. United States 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. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Clinical development of valbenazine for tics associated with Tourette syndrome. [2022]

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

Intermittent theta-burst transcranial magnetic stimulation for treatment of Parkinson disease. [2021]

12. Estonia 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. [2020]

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

Corticospinal integrity and motor impairment predict outcomes after excitatory repetitive transcranial magnetic stimulation: a preliminary study. [2016]

14. England 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. [2022]

15. United States 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. [2022]