rTMS for Laryngeal Dystonia

Recruiting at 1 trial location

Overseen By Caitlin Koehler, Lab Manager

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: MGH Institute of Health Professions

Must not be taking: CNS medications

Disqualifiers: Other dystonia, Vocal pathology, Seizure, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 12

Duration: 5 days

25 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are taking medications for other neurologic conditions that affect the central nervous system, you may be excluded from participating.

What data supports the effectiveness of the treatment Repetitive Transcranial Magnetic Stimulation (rTMS) for Laryngeal Dystonia?

Research suggests that low-frequency rTMS can reduce excessive motor output and improve symptoms in various forms of dystonia, including laryngeal dystonia, by enhancing inhibitory processes in the brain. Pilot studies have shown that rTMS can be safe and feasible, with potential benefits in reducing muscle spasms and improving motor symptoms. ^{1 2 3 4 5}

Is rTMS safe for treating laryngeal dystonia?

Research indicates that repetitive transcranial magnetic stimulation (rTMS) is generally safe and tolerable for treating various forms of dystonia, including laryngeal dystonia. Studies have shown that rTMS can be safely administered to both healthy individuals and those with dystonia, with no significant adverse effects reported. ^{1 4 5 6 7}

How is the treatment rTMS unique for laryngeal dystonia?

Repetitive Transcranial Magnetic Stimulation (rTMS) is unique for laryngeal dystonia because it uses magnetic fields to stimulate nerve cells in the brain, aiming to improve the inhibitory processes that are disrupted in this condition. Unlike other treatments, rTMS is non-invasive and focuses on modulating brain activity rather than directly targeting the laryngeal muscles. ^{1 2 3 4 5}

What is the purpose of this trial?

This trial investigates the use of rTMS, a non-invasive procedure using magnetic fields, to help people with laryngeal dystonia. These individuals have voice issues due to muscle spasms, and current treatments are not very effective. rTMS aims to reduce overactivity in brain areas controlling the larynx muscles, potentially improving their voice quality. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique used for treating various neurological and psychiatric conditions by changing brain activity.

Research Team

Teresa J Kimberley, PhD,PT

Principal Investigator

MGH Institute of Health Professions

Eligibility Criteria

This trial is for adults aged 21-85 with Laryngeal Dystonia, who can consent and are at their worst symptom severity even if they're receiving Botox injections. It's not for those with other dystonias, laryngeal cancer, certain neurologic conditions or medications, contraindications to rTMS, essential tremor, recent seizures or past vocal fold surgeries.

Inclusion Criteria

I am between 21 and 85 years old.

I have been diagnosed with Laryngeal Dystonia.

Subject has signed the consent form

Exclusion Criteria

I have laryngeal cancer or a condition affecting my brain or nerves.

I have a type of dystonia.

I have been diagnosed with essential tremor.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (in-person)

Treatment

Participants receive 5 consecutive days of rTMS or sham intervention targeting the left laryngeal motor cortex

5 days

5 visits (in-person)

Follow-up

Participants are monitored for changes in phonatory function and cortical excitability post-intervention

7 days

1 visit (in-person)

Cross-over Treatment

Participants cross-over to receive the alternate intervention (rTMS or sham) after a minimum of 3 months

5 days

5 visits (in-person)

Treatment Details

Interventions

• Repetitive Transcranial Magnetic Stimulation (rTMS)
• Sham rTMS

Trial Overview The study tests repetitive transcranial magnetic stimulation (rTMS), a non-invasive brain stimulation method on people with Laryngeal Dystonia. Participants will be randomly assigned to receive either real rTMS or sham (fake) treatment to compare effects on muscle control in the voice box.

Participant Groups

Group I: repetitive transcranial magnetic stimulation (rTMS) Active Control 1 Intervention

5 consecutive days of rTMS to the individualized, targeted, left laryngeal motor cortex associated with laryngeal function to down-regulate cortical motor signal to intrinsic laryngeal muscles and improve vocal function of individuals with LD.

Group II: Sham rTMS Placebo Group 1 Intervention

5 consecutive days of sham rTMS to the individualized, targeted, left laryngeal motor cortex associated with laryngeal function to down-regulate cortical motor signal to intrinsic laryngeal muscles and improve vocal function of individuals with LD.

Repetitive Transcranial Magnetic Stimulation (rTMS) is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as rTMS for:

• Depression
• Smoking cessation

Approved in European Union as rTMS for:

• Depression

Approved in Canada as rTMS for:

• Depression

Approved in Japan as rTMS for:

• Depression

Who Is Running the Clinical Trial?

MGH Institute of Health Professions

Lead Sponsor

Trials

19

Recruited

2,200+

National Institute on Deafness and Other Communication Disorders (NIDCD)

Collaborator

Trials

377

Recruited

190,000+

Findings from Research

Transcranial magnetic stimulation (TMS) studies reveal that individuals with laryngeal dystonia (LD) exhibit altered cortical silent period (cSP) durations, which may indicate disrupted inhibitory processes in the brain affecting laryngeal muscle control.

Current treatments for LD include standard therapies and emerging approaches like repetitive TMS and laryngeal vibration, suggesting that understanding the neurophysiological mechanisms could lead to improved treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploring Neurophysiological Mechanisms and Treatment Efficacies in Laryngeal Dystonia: A Transcranial Magnetic Stimulation Approach. Rogić Vidaković, M., Šoda, J., Kuluva, JE., et al.[2023]

In an open pilot study of three patients with severe generalized dystonia, low-frequency repetitive transcranial magnetic stimulation (rTMS) applied to the left premotor cortex significantly reduced painful muscle spasms for 3-8 days after treatment.

While the primary benefit was the reduction of spasms, there were also slight improvements in motor function as measured by the Burke, Fahn, and Marsden rating scale, suggesting that rTMS may help alleviate some symptoms of severe dystonia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-frequency repetitive TMS of premotor cortex can reduce painful axial spasms in generalized secondary dystonia: a pilot study of three patients. Lefaucheur, JP., Fénelon, G., Ménard-Lefaucheur, I., et al.[2022]

In individuals with adductor laryngeal dystonia (AdLD), there is reduced intracortical inhibition and more widespread brain activation in the primary motor cortex during a finger tapping task, compared to healthy controls.

The increased correlation between BOLD activation and intracortical inhibition in non-dystonic muscles suggests a potential compensatory mechanism in the brain to manage motor control despite the presence of dystonia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Probing the inhibitory motor circuits in adductor laryngeal dystonia during a dystonia-unrelated task. Kuo, YL., Chen, M., Kimberley, TJ.[2023]

A single session of low-frequency repetitive transcranial magnetic stimulation (rTMS) over the laryngeal motor cortex was found to be safe and well-tolerated in both individuals with adductor laryngeal dystonia (AdLD) and healthy controls, with no adverse effects reported.

While there were no significant changes in intracortical inhibition, the AdLD group showed promising trends towards improved voice quality and reduced phonatory breaks, suggesting potential benefits that warrant further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of low-frequency repetitive transcranial magnetic stimulation in adductor laryngeal dystonia: a safety, feasibility, and pilot study. Prudente, CN., Chen, M., Stipancic, KL., et al.[2023]

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 low-frequency repetitive transcranial magnetic stimulation (rTMS) applied to the premotor cortex, a patient with primary segmental dystonia (PSD) experienced a 50% reduction in neck symptoms as measured by the Burke, Fahn and Marsden torsion dystonia scale.

The results suggest that rTMS may be an effective intervention for reducing specific motor symptoms in patients with PSD, highlighting its potential therapeutic role.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relief of primary cervical dystonia symptoms by low frequency transcranial magnetic stimulation of the premotor cortex: case report. Allam, N., Brasil-Neto, JP., Brandão, P., et al.[2019]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Exploring Neurophysiological Mechanisms and Treatment Efficacies in Laryngeal Dystonia: A Transcranial Magnetic Stimulation Approach. [2023]

2. France pubmed.ncbi.nlm.nih.gov

Low-frequency repetitive TMS of premotor cortex can reduce painful axial spasms in generalized secondary dystonia: a pilot study of three patients. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Probing the inhibitory motor circuits in adductor laryngeal dystonia during a dystonia-unrelated task. [2023]

4. Germany pubmed.ncbi.nlm.nih.gov

Effects of low-frequency repetitive transcranial magnetic stimulation in adductor laryngeal dystonia: a safety, feasibility, and pilot study. [2023]

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

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

6. Germany pubmed.ncbi.nlm.nih.gov

Relief of primary cervical dystonia symptoms by low frequency transcranial magnetic stimulation of the premotor cortex: case report. [2019]

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]