Accelerated TMS for Hand Dystonia

Overseen By Alaa Norain, MBS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Duke University

Must not be taking: Anticholinergics, Benzodiazepines, Muscle relaxants

Disqualifiers: Other dystonia, Parkinsonism, Seizure, 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: 9

Duration: 1 day

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how accelerated transcranial magnetic stimulation (TMS) might assist individuals with focal hand dystonia, a condition causing involuntary muscle contractions in the hand. The study aims to determine if multiple TMS sessions can enhance hand function and provide insights into brain changes with this treatment. Participants will attend both in-person and virtual visits for brain scans and writing behavior analysis. Right-hand dominant individuals diagnosed with isolated focal hand dystonia who can read and sign consent forms are ideal candidates for this trial. As an unphased study, this trial offers a unique opportunity to contribute to groundbreaking research and potentially improve treatment options for focal hand dystonia.

Will I have to stop taking my current medications?

Yes, you will need to stop taking medications used for treating dystonia symptoms, such as anticholinergics, benzodiazepines, and muscle relaxants, at least one month before the study.

What prior data suggests that this TMS protocol is safe for patients with focal hand dystonia?

Research has shown that transcranial magnetic stimulation (TMS) is generally well-tolerated by patients. TMS is a non-invasive treatment that uses magnetic fields to stimulate brain cells. Although the FDA has not yet approved it for treating dystonia, researchers have studied it for other conditions.

One study on TMS safety found a small risk of seizures, though this is rare. Careful screening and adherence to safety guidelines help reduce this risk. Most people do not experience serious side effects. Common side effects include mild headaches or scalp discomfort, which usually resolve quickly.

Overall, TMS has shown promise in improving movement problems in dystonia, such as focal hand dystonia, with manageable safety concerns. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard of care for hand dystonia, which typically involves medications like anticholinergics or botulinum toxin injections, Accelerated TMS (Transcranial Magnetic Stimulation) is a non-invasive technique that targets the brain's primary somatosensory cortex. Researchers are excited about this treatment because it might offer quicker relief by rapidly modulating brain activity, potentially showing results in a shorter time frame than traditional therapies. Additionally, TMS offers a non-drug alternative, reducing the risk of side effects associated with medications. This innovative approach could be a game-changer for those seeking new options for managing hand dystonia.

What evidence suggests that accelerated TMS is effective for hand dystonia?

Research shows that transcranial magnetic stimulation (TMS) can help people with focal hand dystonia, a condition where hand muscles contract uncontrollably. Studies have found that even one session of TMS, targeting specific brain areas, can reduce these symptoms. Although the FDA has not yet approved TMS specifically for dystonia, early results are promising. In this trial, participants will receive either TMS to the primary somatosensory cortex or TMS at a low amplitude as a sham comparator. Research also suggests that multiple TMS sessions might lead to better and longer-lasting improvements. This treatment uses magnetic pulses to stimulate brain areas that control movement, potentially correcting the abnormal brain activity linked to dystonia. ^{3 6 7 8 9}

Who Is on the Research Team?

Noreen Bukhari-Parlakturk, MD PhD

Principal Investigator

Duke Health

Are You a Good Fit for This Trial?

This trial is for adults over 18 with isolated focal hand dystonia, confirmed by a neurologist. Participants must be right-handed, able to give informed consent and literate. Excluded are those with other movement disorders or seizure history, recent drug use or certain treatments like TMS therapy, botulinum toxin injections, specific medications for dystonia symptoms, and recent hand therapy.

Inclusion Criteria

You primarily use your right hand for tasks.

Diagnosed with isolated focal hand by a neurologist.

Must be able to sign an informed consent

Exclusion Criteria

I have a history of seizures.

I have been diagnosed with a movement disorder other than dystonia.

You have any reasons that make it unsafe for you to have a MRI or TMS.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive accelerated TMS sessions, with four sessions administered in a single day

1 day

2 visits (in-person)

Assessment

Participants undergo functional MRI brain scans and engage in writing tasks to evaluate changes in brain function and behavior

4 weeks

6 visits (virtual), 6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at 12, 20, 24, 32, and 40 weeks

40 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Accelerated TMS

Trial Overview The study tests accelerated transcranial magnetic stimulation (TMS) on patients with focal hand dystonia. It involves four TMS sessions in one day and assesses the impact on brain function and writing behavior immediately after, at two weeks and twelve weeks post-treatment using functional MRI scans.

How Is the Trial Designed?

Group I: TMS to primary somatosensory cortex Active Control 1 Intervention

Participants received TMS sessions at primary somatosensory cortex

Group II: TMS at low amplitude to primary somatosensory cortex Placebo Group 1 Intervention

Participants receive TMS at a cortical target at smaller amplitude

Accelerated TMS is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as rTMS for:

• Major Depressive Disorder
• Obsessive Compulsive Disorder

Approved in European Union as rTMS for:

• Major Depressive Disorder
• Obsessive Compulsive Disorder

Approved in United Kingdom as rTMS for:

• Major Depressive Disorder
• Obsessive Compulsive Disorder
• Post-Traumatic Stress Disorder
• Depersonalization Disorder
• Borderline Personality Disorder
• Addiction

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

American Academy of Neurology

Collaborator

Trials

12

Recruited

370+

Published Research Related to This Trial

Theta burst stimulation (TBS) applied to the primary somatosensory cortex (S1) can modulate somatosensory temporal discrimination threshold (STDT) in patients with focal hand dystonia (FHD), but it does not fully normalize STDT values after treatment.

While intermittent TBS (iTBS) decreased STDT values in patients, indicating some level of response, it did not improve writing performance, suggesting that the underlying mechanisms affecting sensory discrimination differ from those causing motor symptoms in FHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Primary somatosensory cortical plasticity and tactile temporal discrimination in focal hand dystonia. Conte, A., Rocchi, L., Ferrazzano, G., et al.[2022]

Patients with cervical dystonia show disrupted cerebellar cortical connectivity and altered cerebellar plasticity compared to healthy controls, as evidenced by transcranial magnetic stimulation results from a study involving 12 patients and 13 controls.

In healthy individuals, cerebellar stimulation can modulate motor cortex excitability, but these effects are absent in patients with cervical dystonia, indicating a significant difference in cerebellar function in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abnormal cerebellar connectivity and plasticity in isolated cervical dystonia. Porcacchia, P., Álvarez de Toledo, P., Rodríguez-Baena, A., et al.[2020]

Cerebellar continuous theta-burst stimulation (cTBS) effectively reduced excitability in the primary motor cortex for healthy subjects and patients with cervical dystonia, but not for those with focal hand dystonia, suggesting a specific inhibitory role of the cerebellum in different types of dystonia.

The study found no correlation between changes in motor cortex excitability and movement abnormalities in patients, indicating that the cerebellar modulation may not directly influence kinematic measures in focal dystonia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of cerebellar theta-burst stimulation on arm and neck movement kinematics in patients with focal dystonia. Bologna, M., Paparella, G., Fabbrini, A., et al.[2018]

Non-invasive brain stimulation techniques like transcranial magnetic stimulation (TMS) reveal that patients with dystonia exhibit reduced inhibition and increased facilitation in motor cortical excitability, indicating altered brain function in this condition.

Deep brain stimulation (DBS) of the globus pallidus internus (GPi) has been shown to improve symptoms of dystonia, including pain and functional disability, while also demonstrating changes in cortical evoked potentials, suggesting a mechanism for restoring motor control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploring the connections between basal ganglia and cortex revealed by transcranial magnetic stimulation, evoked potential and deep brain stimulation in dystonia. Udupa, K., Bhattacharya, A., Chen, R.[2022]

In a study involving 30 participants, including DYT1 gene carriers with and without dystonia, it was found that those with dystonia showed a significantly prolonged response to repetitive transcranial magnetic stimulation (rTMS), indicating heightened brain plasticity.

The lack of response to rTMS in DYT1 gene carriers without dystonia suggests that abnormal brain plasticity may play a crucial role in the development of symptoms in genetically predisposed individuals, highlighting a potential mechanism in the pathogenesis of primary dystonia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abnormalities in motor cortical plasticity differentiate manifesting and nonmanifesting DYT1 carriers. Edwards, MJ., Huang, YZ., Mir, P., et al.[2007]

In a study involving 14 patients with idiopathic focal hand dystonia (FHD) and 14 healthy controls, it was found that techniques like intermittent theta burst stimulation (iTBS) and paired associative stimulation (PAS) did not produce the expected changes in motor evoked potentials (MEPs) in FHD patients, indicating altered brain plasticity.

Additionally, FHD patients showed a lack of expected improvements in motor learning tasks, suggesting that both experimentally-induced and behaviorally-induced plasticity are disrupted in this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abnormal experimentally- and behaviorally-induced LTP-like plasticity in focal hand dystonia. Belvisi, D., Suppa, A., Marsili, L., et al.[2013]

A two-week trial of cerebellar continuous theta burst stimulation (cTBS) in patients with cervical dystonia showed a small but significant clinical improvement of about 15% as measured by the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS).

The stimulation altered cerebellar brain inhibition (CBI) circuits and normalized patterns of cortical plasticity, suggesting that cerebellar-thalamo-cortical circuits could be a promising target for managing symptoms of dystonia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of two weeks of cerebellar theta burst stimulation in cervical dystonia patients. Koch, G., Porcacchia, P., Ponzo, V., et al.[2018]

Repetitive transcranial magnetic stimulation (rTMS) significantly reduced the severity of dystonia symptoms in 66 patients, as measured by the Burke-Fahn-Marsden scale, indicating its efficacy in treating this condition.

The treatment was well-tolerated with minimal side effects, suggesting that rTMS is a safe option for patients with various forms of dystonia, supporting its broader use in rehabilitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of transcranial magnetic stimulation in the treatment of rare forms of muscular dystonia]. Likhachev, SA., Charnukha, TN., Zabrodzets, GV., et al.[2018]

In patients with dystonia who had deep brain stimulation (DBS) electrodes implanted, transcranial magnetic stimulation (TMS) of one motor cortex produced bilateral hand motor responses, indicating a complex interaction between cortical and subcortical pathways.

The study found that ipsilateral responses to TMS were smaller and faster than contralateral responses, suggesting that these responses originate from subcortical activation of corticospinal fibers, which is important for interpreting TMS results in patients with DBS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pseudo-bilateral hand motor responses evoked by transcranial magnetic stimulation in patients with deep brain stimulators. Kühn, AA., Trottenberg, T., Kupsch, A., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4496570/

Mixed effectiveness of rTMS and retraining in the treatment of ... The aim of this study was to determine the functional efficacy of an intervention combining repetitive transcranial magnetic stimulation (rTMS) and sensorimotor ...

2. frontierspartnerships.org frontierspartnerships.org/journals/dystonia/articles/10.3389/dyst.2023.11660/full

Transcranial magnetic stimulation: the road to clinical therapy ... Despite many research studies, transcranial magnetic stimulation (TMS) is not yet an FDA-approved clinical therapy for dystonia patients.

3. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT01884064

Repetitive Transcranial Magnetic Stimulation for the ... Methods: 12 patients with FHD underwent five daily-sessions of 1 Hz rTMS to contralateral dorsal premotor cortex (dPMC). Patients held a pencil and made ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12000667/

Role of Accelerated Continuous Theta Burst Stimulation in ... This case study details the treatment of a 70-year-old male patient with progressive left upper limb dystonia and associated pain.

5. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X24001712

Brain metabolic response to repetitive transcranial ... Our results provide further evidence of abnormal sensory system function in CD and show that a single session of S1 cTBS is sufficient to induce measurable ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06015672

NCT06015672 | Accelerated TMS for Focal Hand Dystonia This study aims to investigate the impact of accelerated transcranial magnetic stimulation (TMS) on brain function and behavior in patients with focal hand ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3260517/

Safety of Theta Burst Transcranial Magnetic Stimulation Transcranial Magnetic Stimulation (TMS) can be used to experimentally manipulate brain activity, and is capable of inducing long-term (on the order of minutes ...

8. cpn.or.kr cpn.or.kr/journal/download_pdf.php?doi=10.9758/cpn.24.1207

Role of Accelerated Continuous Theta Burst Stimulation in ... Emerging evidence points to heightened motor cortex excitability, hyperplasticity of the sensorimotor cortex, and abnormal sensorimotor.

9. sciencedirect.com sciencedirect.com/science/article/pii/S1388245725004596

50 Hz-Repetitive transcranial magnetic stimulation ... This study explores whether 50 Hz-rTMS and intermittent Theta Burst Stimulation (iTBS), of the primary motor (M1) and dorsolateral prefrontal cortex (DLPFC) ...