rTMS for Laryngeal Dystonia

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Teresa J Kimberley, PhD,PT

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: MGH Institute of Health Professions

Must not be taking: CNS medications

Disqualifiers: Other dystonia, Vocal pathology, Seizure, others

No Placebo Group

Approved in 4 Jurisdictions

Trial Summary

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.

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}

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.

Trial 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) (Neuromodulation)
• Sham rTMS (Behavioural Intervention)

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

MGH Institute of Health Professions Boston, MA

Teresa J Kimberley Boston, MA

Who Is Running the Clinical Trial?

MGH Institute of Health Professions Lead Sponsor

National Institute on Deafness and Other Communication Disorders (NIDCD) Collaborator

References

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

Exploring Neurophysiological Mechanisms and Treatment Efficacies in Laryngeal Dystonia: A Transcranial Magnetic Stimulation Approach. [2023] Laryngeal dystonia (LD), known or termed as spasmodic dysphonia, is a rare movement disorder with an unknown cause affecting the intrinsic laryngeal muscles. Neurophysiological studies point to perturbed inhibitory processes, while conventional genetic studies reveal fragments of genetic architecture in LD. The study's aims are to (1) describe transcranial magnetic stimulation (TMS) methodology for studying the functional integrity of the corticospinal tract by stimulating the primary motor cortex (M1) for laryngeal muscle representation and recording motor evoked potentials (MEPs) from laryngeal muscles; (2) evaluate the results of TMS studies investigating the cortical silent period (cSP) in LD; and (3) present the standard treatments of LD, as well as the results of new theoretical views and treatment approaches like repetitive TMS and laryngeal vibration over the laryngeal muscles as the recent research attempts in treatment of LD. Neurophysiological findings point to a shortened duration of cSP in adductor LD and altered cSP duration in abductor LD individuals. Future TMS studies could further investigate the role of cSP in relation to standard laryngological measures and treatment options. A better understanding of the neurophysiological mechanisms might give new perspectives for the treatment of LD.

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] Dystonia is associated with excessive corticospinal motor output. Motor cortex excitability may be reduced by low-frequency repetitive transcranial magnetic stimulation (rTMS) of premotor cortical areas. We report the effects of 1 Hz rTMS applied at 90% of resting motor threshold over the left premotor cortex in an open pilot study of three patients with severe, generalized, secondary dystonia including painful spasms in the proximal and axial musculature. A 20-min session of premotor rTMS was daily performed during 5 consecutive days. The series of rTMS sessions dramatically reduced the painful spasms, for 3-8 days after the last session, without any other significant beneficial effects. However, a slight reduction of the Movement score of the Burke, Fahn and Marsden rating scale was observed for two patients, and of the Disability score for the third one. Low-frequency rTMS of the premotor cortex may improve some specific motor symptoms in severe, generalized dystonia. These results should prompt confirmation in a larger placebo-controlled study.

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

Probing the inhibitory motor circuits in adductor laryngeal dystonia during a dystonia-unrelated task. [2023] The pathophysiology of adductor laryngeal dystonia (AdLD) remains unknown; however, there is growing evidence that dystonia is associated with disruptions in the inhibitory regulation of sensorimotor cortical areas. Using functional MRI (fMRI) and transcranial magnetic stimulation (TMS) complementarily, we previously demonstrated an overly activated laryngeal motor cortex and revealed correlations between blood-oxygen-level dependent (BOLD) activation and intracortical inhibition in a phonation (dystonia-related) task in adductor laryngeal dystonia (AdLD).

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] The effects of neuromodulation are virtually unexplored in adductor laryngeal dystonia (AdLD), a disorder characterized by involuntary contraction of intrinsic laryngeal muscles. Recent findings indicated that intracortical inhibition is reduced in people with AdLD. Low-frequency repetitive transcranial magnetic stimulation (rTMS) induces prolonged intracortical inhibition, but the effects in AdLD are unexplored. This pilot and feasibility study aimed to examine the safety, feasibility, and effects of a single session 1 Hz rTMS over the laryngeal motor cortex (LMC) in people with AdLD and healthy individuals.

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] To evaluate the efficacy and safety of repetitive transcranial magnetic stimulation (rTMS) for the treatment of patients with dystonia.

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] To evaluate the effect of low-frequency repetitive transcranial magnetic stimulation (rTMS) on the symptoms of a patient with primary segmental dystonia (PSD).

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] Dystonia is characterized by abnormal posturing due to sustained muscle contraction, which leads to pain and significant disability. New therapeutic targets are needed in this disorder. The objective of this randomized, sham-controlled, blinded exploratory study is to identify a specific motor system target for non-invasive neuromodulation and to evaluate this target in terms of safety and tolerability in the cervical dystonia (CD) population. Eight CD subjects were given 15-minute sessions of low-frequency (0.2 Hz) repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (MC), dorsal premotor cortex (dPM), supplementary motor area (SMA), anterior cingulate cortex (ACC) and a sham condition with each session separated by at least two days. The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) score was rated in a blinded fashion immediately pre- and post-intervention. Secondary outcomes included physiology and tolerability ratings. The mean change in TWSTRS severity score by site was 0.25 ± 1.7 (ACC), -2.9 ± 3.4 (dPM), -3.0 ± 4.8 (MC), -0.5 ± 1.1 (SHAM), and -1.5 ± 3.2 (SMA) with negative numbers indicating improvement in symptom control. TWSTRS scores decreased from Session 1 (15.1 ± 5.1) to Session 5 (11.0 ± 7.6). The treatment was tolerable and safe. Physiology data were acquired on 6 of 8 subjects and showed no change over time. These results suggest rTMS can modulate CD symptoms. Both dPM and MC are areas to be targeted in further rTMS studies. The improvement in TWSTRS scores over time with multiple rTMS sessions deserves further evaluation.