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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether repetitive transcranial magnetic stimulation (rTMS), a non-invasive brain treatment, can improve voice issues caused by laryngeal dystonia (LD). LD affects throat muscles, leading to a breathy voice and frequent pitch breaks. The study compares real rTMS with a sham (fake) version to determine its effect on reducing overactive throat muscles. Individuals diagnosed with LD who experience severe symptoms, even after Botox injections, might be suitable for this study. As an unphased trial, it offers a unique opportunity to explore new treatment possibilities for those seeking alternatives to existing therapies.

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 prior data suggests that this technique is safe for treating laryngeal dystonia?

Research has shown that repetitive transcranial magnetic stimulation (rTMS) is generally safe and well-tolerated for treating various types of dystonia, a condition causing muscle contractions. In studies, a single session of rTMS targeting the brain area controlling voice muscles proved safe and practical. It enhanced voice quality and sound production. This suggests that rTMS could be a promising new treatment option for voice disorders such as laryngeal dystonia. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Repetitive Transcranial Magnetic Stimulation (rTMS) is unique because it offers a non-invasive approach to treating laryngeal dystonia by targeting the brain's motor cortex. Traditional treatments like botulinum toxin injections focus on muscle relaxation, but rTMS aims to modulate the brain's signals directly, potentially offering a more precise and less invasive solution. Researchers are excited about rTMS because it could improve vocal function in just a few days, providing faster relief than some current options. Additionally, the use of a targeted magnetic field to influence brain activity represents a novel mechanism of action compared to existing therapies.

What evidence suggests that rTMS might be an effective treatment for laryngeal dystonia?

Research shows that repetitive transcranial magnetic stimulation (rTMS), a treatment studied in this trial, may improve symptoms of laryngeal dystonia (LD). In earlier studies, a single rTMS session targeting the brain area controlling the voice box improved voice quality in people with adductor laryngeal dystonia (AdLD). This therapy uses magnetic fields to influence brain activity, potentially relaxing the overactive muscles in the voice box. Another study found varying levels of voice improvement in people with LD after treatments like rTMS. Although more research is needed, these findings suggest that rTMS could benefit people with LD. Participants in this trial may receive either rTMS or a sham rTMS treatment to assess its effectiveness. ^{1 2 4 6 7}

Who Is on the Research Team?

Teresa J Kimberley, PhD,PT

Principal Investigator

MGH Institute of Health Professions

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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 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]

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]

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8858301/

Effects of low-frequency repetitive transcranial magnetic ...

One rTMS session over the LMC is safe and feasible, and demonstrated trends of beneficial effects on voice quality and phonatory function in AdLD.

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02957942?term=rtms&viewType=Table&rank=6

NCT02957942 | rTMS in Spasmodic Dysphonia

The goal of this pilot project is to determine if brain excitability of the laryngeal motor cortex can be changed with low-frequency inhibitory repetitive ...

3.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0892199725001110

Neuromodulation for Laryngeal Dystonia: A Systematic ...

All included studies reported various degrees of improvement in patients' voice symptoms with the neuromodulation therapy used. ... No significant ...

4.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/34859288/

Effects of low-frequency repetitive transcranial magnetic ...

One rTMS session over the LMC is safe and feasible, and demonstrated trends of beneficial effects on voice quality and phonatory function in ...

5.

mdpi.com

mdpi.com/2077-0383/11/12/3453

A Narrative Review and Two Case Reports Applying TMS ...

Previous work using TMS has indicated reduced inhibition to be characteristic of focal laryngeal dystonia (LD), hand dystonia, cervical dystonia, and spasmodic ...

6.

sciencedirect.com

sciencedirect.com/science/article/pii/S1935861X20300565

Transcranial magnetic stimulation and functional ...

Transcranial magnetic stimulation and functional magnet resonance imaging evaluation of adductor spasmodic dysphonia during phonation.

7.

withpower.com

withpower.com/trial/phase-dystonia-5-2021-4f86a

rTMS for Laryngeal Dystonia

Research indicates that repetitive transcranial magnetic stimulation (rTMS) is generally safe and tolerable for treating various forms of dystonia, including ...