DBS for Spasmodic Dysphonia

Overseen By Danielle Pietramala, BSc

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of British Columbia

Must be taking: Botox

Disqualifiers: Muscle tension dysphonia, Vocal tremor, Neurodegenerative disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 12 months

16 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing Deep Brain Stimulation (DBS) for patients with Spasmodic Dysphonia who do not respond well to current treatments. DBS involves placing tiny electrodes in the brain to send electrical signals that help reduce muscle spasms and improve speech. Deep brain stimulation (DBS) is a promising new therapy for patients with spasmodic dysphonia (SD), showing good clinical effects in preliminary trials.

Do I need to stop my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, since participants must be receiving Botox treatments, it seems you may need to continue with those.

Is Deep Brain Stimulation (DBS) generally safe for humans?

Deep Brain Stimulation (DBS) has been used safely in humans for various conditions, including Parkinson's disease and essential tremor, although speech impairment can be a side effect. In studies for spasmodic dysphonia, DBS has shown improvements in symptoms with no major safety concerns reported. ^{1 2 3 4 5}

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

Deep Brain Stimulation (DBS) is a unique treatment for spasmodic dysphonia because it targets the brain's neural circuits directly, unlike the standard treatment of botulinum toxin injections which temporarily weaken the throat muscles. DBS offers a more permanent solution by addressing the neurological cause of the condition, potentially reducing the need for frequent treatments. ^{1 2 3 5 6}

What data supports the effectiveness of the treatment Deep Brain Stimulation (DBS) for Spasmodic Dysphonia?

Preliminary results from a study showed that Deep Brain Stimulation (DBS) led to improvements in spasmodic dysphonia symptoms, especially with stimulation on one side of the brain. Additionally, patients with both spasmodic dysphonia and essential tremor experienced unexpected improvements in their voice symptoms after undergoing DBS for their tremor. ^{1 2 3 7 8}

Who Is on the Research Team?

Christopher R Honey, MD

Principal Investigator

University of British Columbia

Are You a Good Fit for This Trial?

This trial is for individuals with spasmodic dysphonia who are currently receiving Botox treatments. It's not suitable for those with muscle tension dysphonia, vocal tremor, mild symptoms, neurodegenerative diseases, laryngeal denervation surgery or intracranial pathology. Also excluded are patients with MRI contraindications like metal implants or certain medical devices.

Inclusion Criteria

I have been diagnosed with spasmodic dysphonia by two different teams.

I am currently receiving Botox treatments.

Exclusion Criteria

I have muscle tension in my voice or a shaky voice.

I have had surgery to cut the nerves to my voice box.

I do not have any MRI contraindications such as metal implants, certain tattoos, or pregnancy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Phase 1 Evaluation

Patients are evaluated by a laryngologist, a speech language pathologist, and a psychiatrist to confirm diagnosis and eligibility for surgery

2-4 weeks

Multiple visits (in-person)

Phase 2 Evaluation

Patients undergo further evaluation at the Indiana University Health Voice Centre, including high-speed videostroboscopy and acoustic recordings

2-4 weeks

Multiple visits (in-person)

Treatment

Randomized crossover trial with DBS On and DBS Off phases, followed by an open-label phase with active stimulation

12 months

Regular visits for monitoring and adjustments

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Deep Brain Stimulation

Trial Overview The trial is testing Deep Brain Stimulation (DBS) as a treatment for spasmodic dysphonia. Participants will undergo a surgical procedure to implant electrodes in the brain and receive electrical stimuli to potentially alleviate involuntary muscle contractions affecting speech.

How Is the Trial Designed?

Group I: DBS On Experimental Treatment 1 Intervention

Group II: DBS Off Placebo Group 1 Intervention

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?

University of British Columbia

Lead Sponsor

Trials

1,506

Recruited

2,528,000+

Published Research Related to This Trial

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]

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]

Citations

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

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

3. 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]

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

Abnormal striatal dopaminergic neurotransmission during rest and task production in spasmodic dysphonia. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Brain structural changes in spasmodic dysphonia: A multimodal magnetic resonance imaging study. [2017]

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

Treatment of dysarthria following subthalamic nucleus deep brain stimulation for Parkinson's disease. [2022]

7. 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]

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

Thalamic Deep Brain Stimulation for Spasmodic Dysphonia: A Phase I Prospective Randomized Double-Blind Crossover Trial. [2021]