TMS for Cervical 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 disorder, others

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

Compensation: Varies

Number of Visits: 11

Duration: 1 day per visit

50 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking medications used for treating dystonia symptoms, such as anticholinergics, benzodiazepines, and muscle relaxants, at least one month before the study.

What data supports the effectiveness of the treatment fMRI-guided Individualized TMS for Cervical Dystonia?

Research shows that transcranial magnetic stimulation (TMS) can change brain activity in people with dystonia, a movement disorder, and may help treat it. Studies on similar conditions, like focal hand dystonia, suggest that TMS can be a promising treatment option. ^{1 2 3 4 5}

Is transcranial magnetic stimulation (TMS) safe for humans?

Research shows that repetitive transcranial magnetic stimulation (rTMS) is generally safe and tolerable for people with cervical dystonia, with no significant changes in physiology over time. ^{3 5 6 7 8}

How is the treatment fMRI-guided Individualized TMS unique for cervical dystonia?

This treatment is unique because it uses fMRI (functional magnetic resonance imaging) to guide the application of TMS (transcranial magnetic stimulation), allowing for personalized targeting of brain areas involved in cervical dystonia. This approach aims to modulate brain activity more precisely compared to standard TMS, potentially improving treatment outcomes by addressing individual differences in brain activation patterns. ^{3 4 8 9 10}

What is the purpose of this trial?

This study aims to investigate the impact of accelerated transcranial magnetic stimulation (TMS) on brain function and behavior in patients with focal cervical dystonia. Previous research demonstrated that individualized TMS improved writing behavior in focal hand dystonia after one session. In this study, we aim to expand the application on TMS on focal cervical dystonia. The current study administers four TMS sessions in a day. The research involves 9 in-person visits. The effect of TMS will be assessed using functional MRI brain scans and behavioral measurements. The risk of TMS includes seizures; the potential risk of seizures from TMS is mitigated through careful screening, adhering to safety guidelines. The study's main benefit is enhancing dystonic behavior and deepening the understanding of brain changes caused by TMS in cervical dystonia, paving the way for further advancements in clinical therapy for this condition.

Research Team

Noreen Bukhari-Parlakturk, MD PhD

Principal Investigator

Duke Health

Eligibility Criteria

This trial is for individuals with conditions like isolated focal hand dystonia, general dystonia, or torticollis. Participants should be able to attend 10 in-person visits and undergo MRI scans and behavior analysis. The study excludes those at risk of seizures or who don't meet the safety guidelines for TMS.

Inclusion Criteria

Must be able to sign an informed consent

I have been diagnosed with focal hand dystonia by a neurologist.

Must be literate

Exclusion Criteria

I have a history of seizures.

I haven't had TMS therapy for any reason in the last month.

I haven't had hand therapy in the last month.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive accelerated TMS sessions, with four sessions administered in a single day during two in-person visits.

1 day per visit

2 visits (in-person)

Assessment

Changes in brain function and behavior are evaluated using functional MRI and behavioral assays after each TMS session.

Approximately 4 weeks

7 visits (in-person)

Follow-up

Participants are monitored for changes in neck angles and brain activity post-TMS and potentially post-DBS.

Approximately 7 months

2 visits (in-person)

Treatment Details

Interventions

• fMRI-guided Individualized TMS

Trial Overview The study tests whether four sessions of accelerated transcranial magnetic stimulation (TMS) can improve brain function and reduce symptoms in patients with focal hand dystonia. It includes fMRI brain scans before and after treatment to observe changes.

Participant Groups

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

Participants received TMS sessions at primary somatosensory cortex

Group II: sham TMS Placebo Group 1 Intervention

Participants receive sham TMS

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+

Findings from Research

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 a study involving 8 subjects with cervical dystonia, low-frequency repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex and dorsal premotor cortex showed significant improvement in dystonia symptoms, as indicated by a decrease in the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) scores.

The treatment was found to be safe and tolerable, suggesting that rTMS could be a promising non-invasive therapeutic option for managing cervical dystonia, warranting further investigation into its efficacy and optimal targeting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation in cervical dystonia: effect of site and repetition in a randomized pilot trial. Pirio Richardson, S., Tinaz, S., Chen, R.[2020]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Patients with focal arm dystonia have increased sensitivity to slow-frequency repetitive TMS of the dorsal premotor cortex. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation in dystonia. [2013]

3. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of transcranial magnetic stimulation in the treatment of rare forms of muscular dystonia]. [2018]

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

Focal hand dystonia: individualized intervention with repeated application of repetitive transcranial magnetic stimulation. [2021]

5. France pubmed.ncbi.nlm.nih.gov

Cortical neurophysiology of primary isolated dystonia and non-dystonic adults: A meta-analysis. [2021]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Reduced cerebral cortex inhibition in dystonia: direct evidence in humans. [2009]

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

Repetitive transcranial magnetic stimulation in cervical dystonia: effect of site and repetition in a randomized pilot trial. [2020]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Pseudo-bilateral hand motor responses evoked by transcranial magnetic stimulation in patients with deep brain stimulators. [2019]

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

Modulatory effects of 5Hz rTMS over the primary somatosensory cortex in focal dystonia--an fMRI-TMS study. [2021]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Reduced parietal activation in cervical dystonia after parietal TMS interleaved with fMRI. [2012]