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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether transcranial magnetic stimulation (TMS), a non-invasive brain treatment, can reduce symptoms in people with functional movement disorders (FMD), which cause involuntary movements without a known medical cause. Participants will be randomly assigned to one of two groups: one receiving real TMS treatment and the other receiving a placebo version for comparison. This trial suits individuals diagnosed with FMD by a neurologist. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important early-stage findings.

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 prior data suggests that transcranial magnetic stimulation (TMS) is safe for treating functional movement disorder?

Research has shown that intermittent theta burst stimulation (iTBS) is generally safe and well-tolerated. In studies, participants did not experience serious side effects, and no seizures occurred. The U.S. FDA approved iTBS for treating depression, indicating it is a safe method for brain stimulation. This non-invasive treatment has also been used safely in people with depression and stroke patients to help improve their symptoms. Overall, iTBS appears to be a safe option for those considering joining a trial for functional movement disorders. ^{1 2 3 4 5}

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

Researchers are excited about Intermittent Theta Burst Stimulation (iTBS) for Functional Movement Disorder because it offers a novel approach compared to current treatments like physical therapy, medication, and cognitive-behavioral therapy. Unlike these conventional methods that often take a more generalized approach, iTBS specifically targets brain activity using magnetic pulses to potentially reset dysfunctional neural circuits. This non-invasive technique can rapidly induce changes in brain function, which might lead to quicker improvements in symptoms. Additionally, iTBS's ability to precisely focus on affected brain areas could offer more personalized and effective treatment outcomes for patients.

What evidence suggests that Intermittent Theta Burst Stimulation might be an effective treatment for Functional Movement Disorder?

Research has shown that intermittent theta burst stimulation (iTBS) can improve symptoms for various conditions. In this trial, participants will receive either active TMS stimulation using an active TMS coil or sham TMS stimulation using a sham coil. One study found that ten sessions of iTBS over five days led to 79% of participants experiencing a significant reduction in symptoms, compared to those who received a sham treatment. Another study demonstrated that iTBS safely and effectively reduced depression symptoms in teenagers after just two days. Additionally, iTBS has successfully helped people regain arm movement and influenced brain activity. These findings suggest that iTBS might aid movement disorders by altering brain patterns related to movement. ^{2 4 6 7 8}

Who Is on the Research Team?

Debra J Ehrlich, M.D.

Principal Investigator

National Institute of Neurological Disorders and Stroke (NINDS)

Are You a Good Fit for This Trial?

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 have been diagnosed with a functional movement disorder by a neurologist.

Exclusion Criteria

Alcohol or substance use disorder

Pregnancy

I have a heart condition that is moderate to severe.

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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 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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11238064/

Accelerated Intermittent Theta-Burst Stimulation and ... Ten sessions per day for 5 days achieved 79% remission in a sham-controlled randomized clinical trial—substantially better than remission rates ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165032725000023

Efficacy study of intermittent theta burst stimulation(iTBS) in ... The current study suggests that two days of active iTBS to the DLPFC region can rapidly, safely, and effectively improve depressive symptoms in adolescents ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10602812/

The effectiveness of intermittent theta burst stimulation for ... Several studies have demonstrated the effectiveness of iTBS in restoring upper limb function and modulating cortical excitability.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05155059

Non-invasive Intermittent Theta Burst Stimulation of the ... The purpose of this protocol is to investigate efficacy of intermittent theta burst stimulation (iTBS) targeting the left dorsolateral prefrontal cortex (DLPFC) ...

5. nature.com nature.com/articles/s41380-024-02630-5

Theta burst stimulation for depression: a systematic review ... Theta burst stimulation (TBS) presents as a more efficient and potentially more effective therapeutic modality than conventional repetitive transcranial ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8617062/

A Systematic Review of the Safety and Tolerability of Theta ... All participants tolerated iTBS without significant adverse events. No complications, such as seizures, occurred in any of the participants. One participant ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03263013?cond=movement%20disorders&rank=10

Non-invasive Intermittent Theta Burst Stimulation of the ... To test if intermittent theta burst stimulation (iTBS) affects brain areas involved in FMD symptoms. Also, to look at the effect of iTBS on mood and motor ...

8. frontiersin.org frontiersin.org/journals/neurology/articles/10.3389/fneur.2024.1450435/full

Effect of intermittent theta burst stimulation on upper limb ... The comprehensive evidence suggests that iTBS has superior effects in improving upper limb function and activities of daily living in stroke patients.