Deep Brain Stimulation for Spasmodic Dysphonia and Tremor

Recruiting at 3 trial locations

Overseen By Kristina Simonyan, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Massachusetts Eye and Ear Infirmary

Disqualifiers: Hearing loss, Cortical venous anatomy, 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: 1

120 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial studies how Deep Brain Stimulation (DBS) affects voice control in patients with dystonia and essential tremor. DBS sends electrical impulses to brain areas that manage movement, aiming to improve voice function in these patients. Deep Brain Stimulation (DBS) has been used to treat severe movement disorders, including Parkinson's disease, dystonia, and essential tremor.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Deep Brain Stimulation for Spasmodic Dysphonia and Tremor?

Research shows that Deep Brain Stimulation (DBS) can improve symptoms of spasmodic dysphonia (a voice disorder) and tremor. In a study, patients with both conditions experienced significant improvement, especially with stimulation on one side of the brain. This suggests DBS could be a promising treatment for these voice and movement disorders. ^{1 2 3 4 5}

Is Deep Brain Stimulation generally safe for humans?

Deep Brain Stimulation (DBS) has been used for various movement disorders like Parkinson's disease, but it can have complications such as infections, lead migrations, and device malfunctions. Some patients may experience neurobehavioral effects, and in certain cases, serious complications like cerebral bleeds or device-related trauma may occur, requiring further surgery. ^{6 7 8 9 10}

How is the treatment Deep Brain Stimulation (DBS) different from other treatments for spasmodic dysphonia?

Deep Brain Stimulation (DBS) is unique because it involves implanting electrodes in the brain to modulate neural circuits, offering a potentially long-lasting improvement for spasmodic dysphonia without the need for repeated injections like botulinum toxin A (BTX). Unlike BTX, which requires regular administration, DBS can provide continuous symptom relief and may address underlying neural pathways involved in the condition. ^{1 2 11 12 13}

Research Team

Kristina Simonyan, MD, PhD

Principal Investigator

Massachusetts Eye and Ear

Eligibility Criteria

This trial is for adults aged 18-80 with voice disorders due to dystonia or essential tremor, who are candidates for deep brain stimulation (DBS) surgery. Participants must be able to follow instructions, complete training, and give informed consent. They should not have obstructive venous anatomy, significant hearing loss, or inability to perform required tasks.

Inclusion Criteria

I can follow test instructions, complete training, and give informed consent.

I am between 18 and 80 years old.

I am approved for DBS surgery for my essential tremor or dystonia by a specialist team.

Exclusion Criteria

Your brain's veins could get in the way of placing electrodes during surgery.

I can understand and perform the tasks required in the study protocol.

I have significant hearing loss.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery and Data Collection

Electrophysiological data collection during DBS surgery for patients with dystonia or tremor

1 day

1 visit (in-person)

Follow-up

Participants are monitored for changes in voice and motor function using clinical rating scales

5 years

Treatment Details

Interventions

• Deep Brain Stimulation

Trial Overview The study aims to understand how often voice disorders occur in patients with dystonia and essential tremor treated with DBS. It will explore the changes in brain imaging and activity related to voice dysfunction before and after the treatment.

Participant Groups

Group I: Electrophysiological signal data collection Experimental Treatment 1 Intervention

Patients diagnosed with dystonia or tremor who are recommended for DBS surgery. Electrophysiological data will be collected at the time of DBS surgery.

Deep Brain Stimulation is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Deep Brain Stimulation for:

• Essential tremor
• Parkinson's disease
• Dystonia
• Obsessive-compulsive disorder
• Epilepsy
• Chronic pain
• Stroke-related motor deficits (under investigation)

Approved in European Union as Deep Brain Stimulation for:

• Essential tremor
• Parkinson's disease
• Dystonia
• Obsessive-compulsive disorder
• Epilepsy
• Chronic pain

Approved in Canada as Deep Brain Stimulation for:

• Essential tremor
• Parkinson's disease
• Dystonia
• Obsessive-compulsive disorder
• Epilepsy
• Chronic pain

Who Is Running the Clinical Trial?

Massachusetts Eye and Ear Infirmary

Lead Sponsor

Trials

115

Recruited

15,000+

UMASS Memorial Medical Center

Collaborator

Trials

4

Recruited

3,900+

University of Iowa

Collaborator

Trials

486

Recruited

934,000+

University of Utah

Collaborator

Trials

1,169

Recruited

1,623,000+

Massachusetts General Hospital

Collaborator

Trials

3,066

Recruited

13,430,000+

University of California, San Francisco

Collaborator

Trials

2,636

Recruited

19,080,000+

Findings from Research

Deep brain stimulation (DBS) shows promising results for treating spasmodic dysphonia (SD), with unilateral left thalamic stimulation providing significant clinical effects in a small trial of 6 right-handed patients.

In two patients with both essential tremor and SD, bilateral thalamic DBS led to the most improvement, but unilateral stimulation was also effective, suggesting that the treatment's efficacy may depend on the patient's handedness and the dominant hemisphere for speech.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep Brain Stimulation for Spasmodic Dysphonia: A Blinded Comparison of Unilateral and Bilateral Stimulation in Two Patients. Krüger, MT., Hu, A., Honey, CR.[2021]

Deep brain stimulation (DBS) has shown efficacy in treating vocal tremor, a challenging disorder, based on a review of literature from 2002 to 2011, indicating its potential as a treatment option.

Despite its effectiveness, DBS may be underutilized, and there is a need for collaboration among laryngologists, neurosurgeons, and other specialists to further investigate its safety and efficacy for voice disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for treatment of voice disorders. Hawkshaw, MJ., Sataloff, RT.[2012]

In a study of 128 patients with spasmodic dysphonia (SD) and 146 voice disorder controls, 26% of SD patients exhibited vocal tremor and 21% had nonvocal tremor, indicating a high prevalence of tremor in this population.

Patients with SD were found to be 2.8 times more likely to have tremor compared to the control group, highlighting the need for tremor evaluations in SD patients, especially since only 35% had previously consulted a neurologist for related issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Coprevalence of tremor with spasmodic dysphonia: a case-control study. White, LJ., Klein, AM., Hapner, ER., et al.[2021]

In a study of 12 patients with essential tremor and vocal tremor, both deep brain stimulation (DBS) and focused ultrasound (FUS) significantly reduced vocal tremor, as shown by a decrease in fundamental frequency variability from 18.3% to 6.3% after intervention.

The focused ultrasound group showed a reduction in vocal tremor from 22.0% to 6.7% post-ablation, while the DBS group experienced a decrease from 15.7% to 6.0% with stimulation, indicating both procedures are effective in improving vocal tremor in patients with dysphonia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Voice Improvement After Essential Tremor Treatment via Focused Ultrasound and Deep Brain Stimulation. Larner, P., Jonas, R., Gutierrez, CN., et al.[2023]

Deep brain stimulation (DBS) significantly improves voice tremor severity and voice-related quality of life in adults with vocal tremors, based on a systematic review of nine studies involving 61 patients.

Specifically, stimulation of the Vim area of the brain shows notable benefits for reducing voice tremors, while stimulation of the STN area does not provide clear advantages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Voice-Related Outcomes in Deep Brain Stimulation in Patients with Vocal Tremor: A Systematic Review and Meta-Analysis. Lu, F., Zhao, K., Wu, Y., et al.[2023]

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) significantly improved motor symptoms in a 44-year-old woman with Parkinson's disease, but also caused uncontrollable laughter, highlighting the potential for neurobehavioral side effects.

The use of directional electrodes allowed for more precise stimulation, which helped to minimize undesirable side effects while optimizing motor improvement, suggesting that careful programming and electrode placement are crucial for effective DBS therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-motor Adverse Effects Avoided by Directional Stimulation in Parkinson's Disease: A Case Report. Alonso-Frech, F., Fernandez-Garcia, C., Gómez-Mayordomo, V., et al.[2022]

Deep brain stimulation (DBS) is a safe and effective surgical treatment for advanced Parkinson's disease, with a low incidence of serious complications, as shown in a study of 130 patients over several years.

In this study, 62% of patients experienced no complications, and the most common issues were minor, such as aborted procedures (5.14%) and seizures (4.7%), indicating that DBS has a favorable safety profile compared to other surgical options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications in subthalamic nucleus stimulation surgery for treatment of Parkinson's disease. Review of 272 procedures. Seijo, FJ., Alvarez-Vega, MA., Gutierrez, JC., et al.[2019]

A rare complication of unilateral cyst formation at the tip of a deep brain stimulation (DBS) electrode occurred in an older woman with advanced Parkinson's disease, leading to new neurological deficits due to edema.

Stereotactic aspiration was successfully used to drain the cyst fluid, allowing for rapid regression of symptoms while keeping the DBS electrode in place, highlighting a safe and effective intervention for this complication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of Unilateral Peri-Lead Edema Into Large Cystic Cavitation After Deep Brain Stimulation: A Case Report. Lu, Y., Qiu, C., Chang, L., et al.[2022]

A review of 221 unique adverse events related to deep brain stimulation (DBS) devices for Parkinson's disease revealed that the most common complications were infections (16.2%) and lead migrations (8.6%).

Over 40% of the reported adverse events required patients to return to the operating room for device explantation or revision, highlighting the need for further research to improve the safety and reliability of DBS systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterizing Complications of Deep Brain Stimulation Devices for the Treatment of Parkinsonian Symptoms Without Tremor: A Federal MAUDE Database Analysis. Bennett, J., MacGuire, J., Novakovic, E., et al.[2023]

Deep brain stimulation (DBS) is an effective surgical treatment for movement disorders like Parkinson's disease and dystonia, targeting areas such as the subthalamic nucleus (STN) and globus pallidus internus (GPi).

DBS not only improves motor functions but can also affect cognitive and emotional aspects of patients, highlighting the need for careful target selection and consideration of potential adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Critical reappraisal of DBS targeting for movement disorders. Guzzi, G., Della Torre, A., Chirchiglia, D., et al.[2017]

In a study involving 5 subjects with spasmodic dysphonia, electrical stimulation of the thyroarytenoid muscle led to significant improvements in voice evaluations for 4 out of the 5 participants, suggesting the treatment's efficacy.

The study demonstrated the feasibility of implanting an electrical stimulation device in the thyroarytenoid muscle, indicating potential for a new treatment approach for spasmodic dysphonia through neuromodulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of spasmodic dysphonia with a neuromodulating electrical implant. Pitman, MJ.[2014]

In a review of cases from 2012 to 2020, three patients with adductor spasmodic dysphonia (SD) and essential tremor showed significant improvement in their voice and limb tremors after undergoing bilateral thalamic deep brain stimulation (DBS).

The improvement in SD was specifically noted when higher stimulation amplitudes or wider pulse widths were used, indicating that the effectiveness of DBS for SD may depend on the settings used during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adductor Spasmodic Dysphonia Improves with Bilateral Thalamic Deep Brain Stimulation: Report of 3 Cases Done Asleep and Review of Literature. Evidente, VGH., Ponce, FA., Evidente, MH., et al.[2021]

Unilateral thalamic deep brain stimulation (DBS) significantly improved vocal function in a 79-year-old woman with spasmodic dysphonia (SD) and essential tremor, as shown by a decrease in Unified Spasmodic Dysphonia Rating Scale scores and improved voice-related quality of life.

The study found that stimulation of the ventral intermediate (Vim) nucleus was more effective than stimulation of the ventral oralis anterior (Voa) nucleus, suggesting that targeting specific neural circuits can enhance treatment outcomes for SD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of unilateral thalamic deep brain stimulation on the vocal dysfunction in a patient with spasmodic dysphonia: interrogating cerebellar and pallidal neural circuits. Poologaindran, A., Ivanishvili, Z., Morrison, MD., et al.[2019]

References

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

Deep Brain Stimulation for Spasmodic Dysphonia: A Blinded Comparison of Unilateral and Bilateral Stimulation in Two Patients. [2021]

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

Deep brain stimulation for treatment of voice disorders. [2012]

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

Coprevalence of tremor with spasmodic dysphonia: a case-control study. [2021]

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

Voice Improvement After Essential Tremor Treatment via Focused Ultrasound and Deep Brain Stimulation. [2023]

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

Voice-Related Outcomes in Deep Brain Stimulation in Patients with Vocal Tremor: A Systematic Review and Meta-Analysis. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Non-motor Adverse Effects Avoided by Directional Stimulation in Parkinson's Disease: A Case Report. [2022]

7. Austria pubmed.ncbi.nlm.nih.gov

Complications in subthalamic nucleus stimulation surgery for treatment of Parkinson's disease. Review of 272 procedures. [2019]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Development of Unilateral Peri-Lead Edema Into Large Cystic Cavitation After Deep Brain Stimulation: A Case Report. [2022]

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

Characterizing Complications of Deep Brain Stimulation Devices for the Treatment of Parkinsonian Symptoms Without Tremor: A Federal MAUDE Database Analysis. [2023]

10. Italy pubmed.ncbi.nlm.nih.gov

Critical reappraisal of DBS targeting for movement disorders. [2017]

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

Treatment of spasmodic dysphonia with a neuromodulating electrical implant. [2014]

12. England pubmed.ncbi.nlm.nih.gov

Adductor Spasmodic Dysphonia Improves with Bilateral Thalamic Deep Brain Stimulation: Report of 3 Cases Done Asleep and Review of Literature. [2021]

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

The effect of unilateral thalamic deep brain stimulation on the vocal dysfunction in a patient with spasmodic dysphonia: interrogating cerebellar and pallidal neural circuits. [2019]