TMS for Functional Movement Disorder

Overseen By Hyun Joo Cho, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)

Must not be taking: Buproprion

Disqualifiers: Psychosis, Epilepsy, Cardiac disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 10

Duration: 1 week

30 Participants Needed

Trial Summary

What is the purpose of this trial?

Background: Functional movement disorders (FMD) involve involuntary movements that are not due to a recognized neurological or medical cause. FMD can cause major disability. Researchers want to learn more to create better treatments for FMD. Objective: To test whether non-invasive brain stimulation using transcranial magnetic stimulation (TMS) improves FMD symptoms. Eligibility: People between the ages of 18 and 80 who have been diagnosed with FMD by a neurologist. Design: Participants will be randomly assigned to one of two groups. One group is an active brain stimulation group and the other is a sham brain stimulation group. Participants will have a baseline visit. This will include: Neurological exam Questionnaires Urine test Brain MRI: Participants will lie in a machine that takes pictures of the body. They will be asked to respond to images on a screen while in the scanner. Within 2 weeks of the baseline visit, participants will begin 5 daily sessions of TMS. The active group will have stimulation delivered to the brain via a coil. In the sham group, a dummy coil will be used that will not deliver stimulation. A total of three 3-minute cycles will be done in one visit. There will be 20-minute breaks between the cycles. Participants will have visits 1 month, 2 months, and 6 months after their last day of TMS. Their FMD symptoms will be evaluated. They will complete health questionnaires. These visits can be in person or virtual.

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 cannot participate if you are taking Buproprion (Wellbutrin).

What data supports the effectiveness of the treatment Intermittent Theta Burst Stimulation (iTBS) for Functional Movement Disorder?

Intermittent Theta Burst Stimulation (iTBS) has shown effectiveness in improving motor function in conditions like Parkinson's disease and multiple sclerosis, and it is also used for treating depression. This suggests it may help with movement disorders by influencing brain activity related to motor control. ^{1 2 3 4 5}

Is theta burst stimulation (TBS) safe for humans?

Theta burst stimulation (TBS), including intermittent theta burst stimulation (iTBS), is generally considered safe for humans, with most adverse events being mild and occurring in about 5% of people. However, there is a theoretical risk of seizures, so it should be used with caution, and more research is needed to fully understand the safety of different stimulation settings. ^{1 2 4 6 7}

How is Intermittent Theta Burst Stimulation (iTBS) different from other treatments for Functional Movement Disorder?

Intermittent Theta Burst Stimulation (iTBS) is unique because it is a form of repetitive transcranial magnetic stimulation (rTMS) that can be delivered in just over 3 minutes, making it much quicker than traditional rTMS sessions. It influences brain activity to help improve motor function, which may be beneficial for conditions like Functional Movement Disorder. ^{1 2 4 6 8}

Research Team

Hyun Joo Cho, M.D.

Principal Investigator

National Institute of Neurological Disorders and Stroke (NINDS)

Eligibility Criteria

This trial is for adults aged 18-80 diagnosed with Functional Movement Disorder (FMD) by a neurologist. Participants must be willing to follow the study procedures, not have significant neurological disorders other than FMD, no current psychosis or active suicidal thoughts, and not be pregnant.

Inclusion Criteria

Stated willingness to comply with all study procedures and availability for the duration of the study

Agreement to adhere to Lifestyle Considerations throughout study duration

I am between 18 and 80 years old.

Exclusion Criteria

Alcohol or substance use disorder

Pregnancy

I have a heart condition that is moderate to severe.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Baseline

Participants undergo neurological exam, questionnaires, urine test, and brain MRI

1 day

1 visit (in-person)

Treatment

Participants receive 5 daily sessions of TMS, either active or sham

1 week

5 visits (in-person)

Follow-up

Participants' FMD symptoms are evaluated and health questionnaires are completed

6 months

3 visits (in-person or virtual)

Treatment Details

Interventions

• Intermittent Theta Burst Stimulation

Trial Overview The trial tests if non-invasive brain stimulation using Theta Burst Stimulation (TMS) can improve symptoms of FMD. Participants are randomly assigned to receive either real TMS or sham (fake) stimulation over five daily sessions, followed by evaluations up to six months after treatment.

Participant Groups

Group I: Treatment Experimental Treatment 1 Intervention

Active TMS stimulation using an active TMS coil

Group II: Control Placebo Group 1 Intervention

Sham TMS stimulation using a sham coil

Intermittent Theta Burst Stimulation is already approved in United States, European Union for the following indications:

Approved in United States as iTBS for:

• Treatment-resistant depression

Approved in European Union as iTBS for:

• Treatment-resistant depression

Who Is Running the Clinical Trial?

National Institute of Neurological Disorders and Stroke (NINDS)

Lead Sponsor

Trials

1,403

Recruited

655,000+

Findings from Research

In a study of 27 participants, a prolonged intermittent theta burst stimulation (piTBS) protocol using 1,800 pulses showed limited effectiveness for major depressive disorder, with only 18.2% of participants achieving a response and 9.1% reaching remission.

Safety and tolerability were concerns, as 18.5% of participants experienced issues, suggesting that while piTBS is a promising approach, further research is needed to optimize its parameters and improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged intermittent theta burst stimulation in the treatment of major depressive disorder: a case series. Richard, M., Noiseux, C., Desbeaumes Jodoin, V., et al.[2022]

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) 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]

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 of 60 patients with treatment-resistant unipolar depression, both intermittent theta burst stimulation (iTBS) and conventional 10 Hz rTMS showed similar efficacy in reducing depression scores and improving quality of life over a 6-month follow-up, with response rates of 36.7% for iTBS and 33.3% for rTMS.

iTBS is highlighted as a more time-efficient and cost-effective option compared to rTMS, suggesting it could be a valuable treatment alternative for patients with severe depression who have not responded to multiple antidepressant trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent theta burst stimulation (iTBS) versus 10 Hz high-frequency repetitive transcranial magnetic stimulation (rTMS) to alleviate treatment-resistant unipolar depression: A randomized controlled trial (THETA-DEP). Bulteau, S., Laurin, A., Pere, M., et al.[2022]

Intermittent theta-burst stimulation (iTBS) and high-frequency rTMS (HF-rTMS) show similar efficacy in treating treatment-resistant depression (TRD), with response rates of 48.0% for iTBS and 45.5% for HF-rTMS based on two high-quality randomized controlled trials involving 474 participants.

Both iTBS and HF-rTMS have comparable safety profiles, with similar rates of discontinuation and adverse events, such as headaches, indicating that iTBS is a safe alternative to HF-rTMS for patients with TRD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of intermittent theta burst stimulation versus high-frequency repetitive transcranial magnetic stimulation for patients with treatment-resistant depression: a systematic review. Lan, XJ., Yang, XH., Qin, ZJ., et al.[2023]

Theta burst stimulation (TBS) is a promising technique for altering brain excitability, with a review of studies showing that adverse events were mostly mild and occurred in only 5% of subjects, indicating a generally safe profile.

Despite its safety, TBS carries a theoretical higher risk of seizures compared to other stimulation methods, necessitating cautious application and further research into its dosing parameters to better understand seizure risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of theta burst transcranial magnetic stimulation: a systematic review of the literature. Oberman, L., Edwards, D., Eldaief, M., 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. Ireland pubmed.ncbi.nlm.nih.gov

Prolonged intermittent theta burst stimulation in the treatment of major depressive disorder: a case series. [2022]

2. 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]

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

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

4. 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]

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

Intermittent theta burst stimulation (iTBS) versus 10 Hz high-frequency repetitive transcranial magnetic stimulation (rTMS) to alleviate treatment-resistant unipolar depression: A randomized controlled trial (THETA-DEP). [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and safety of intermittent theta burst stimulation versus high-frequency repetitive transcranial magnetic stimulation for patients with treatment-resistant depression: a systematic review. [2023]

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

Safety of theta burst transcranial magnetic stimulation: a systematic review of the literature. [2022]

8. 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]