Sensory Block + Brain Imaging for Spasmodic Dysphonia

Overseen By Kristina Simonyan, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Massachusetts Eye and Ear Infirmary

Must not be taking: CNS drugs

Disqualifiers: Neurological, Psychiatric, Laryngeal, others

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 5 years

165 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The researchers will examine functional neural correlates that differentiate between laryngeal dystonia and voice tremor and contribute to disorder-specific pathophysiology using a cross-disciplinary approach of multimodal brain imaging.

Will I have to stop taking my current medications?

If you are taking medications that affect the central nervous system, you will not be able to participate in the trial. The protocol does not specify other medication restrictions, but you will be asked about all medications during the initial screening.

Is the sensory block and brain imaging treatment for spasmodic dysphonia safe for humans?

The research articles provided do not contain specific safety data for the sensory block and brain imaging treatment using topical bupivacaine in humans. They focus on brain activity changes in spasmodic dysphonia patients but do not address safety concerns. ^{1 2 3 4 5}

How does the treatment of brain imaging differ from other treatments for spasmodic dysphonia?

Brain imaging for spasmodic dysphonia is unique because it focuses on identifying specific brain activity patterns and abnormalities associated with the condition, rather than directly treating the symptoms. This approach helps in understanding the underlying brain mechanisms and could lead to more targeted therapies in the future. ^{1 6 7 8 9}

What data supports the effectiveness of the treatment for spasmodic dysphonia?

The research suggests that treatments like botulinum toxin injections can improve brain processing and reduce symptoms in spasmodic dysphonia by enhancing the brain's ability to control voice-related movements. This indicates that brain imaging and sensory block treatments might also help by targeting similar brain areas involved in voice control. ^{2 3 4 5 7}

Who Is on the Research Team?

Kristina Simonyan, MD, PhD

Principal Investigator

Professor of Otolaryngology - Head and Neck Surgery

Are You a Good Fit for This Trial?

This trial is for native English-speaking, right-handed adults aged 18-80 who are healthy or have laryngeal dystonia or voice tremor. Excluded are those with other neurological issues, psychiatric disorders, certain laryngeal conditions, history of brain/laryngeal surgery affecting anatomy/function, tattoos/objects unsafe for MRI, and use of central nervous system drugs.

Inclusion Criteria

I belong to a diverse racial or ethnic background.

You primarily use your right hand.

I am a native English speaker.

Exclusion Criteria

I am not taking any medications that affect the brain.

I experience muscle contractions without moving or have mirror dystonia.

You have tattoos or metal objects inside your body that can't be taken out for MRI scans.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo sensorimotor modulations and auditory feedback processing using bupivacaine, placebo, and MEG imaging to assess CNS pathophysiology

5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Brain Imaging
• Topical Bupivacaine

Trial Overview The study aims to understand the differences in brain function between laryngeal dystonia and voice tremor using a sensory block with bupivacaine and advanced brain imaging techniques to identify disorder-specific neural activity patterns.

How Is the Trial Designed?

Group I: Spatial and temporal CNS pathophysiology of laryngeal dystonia and voice tremor Experimental Treatment 1 Intervention

Simultaneous fMRI with EEG and MEG imaging will be used to examine neural dynamics during phonation.

Group II: Motor learning and CNS pathophysiology of laryngeal dystonia and voice tremor Experimental Treatment 1 Intervention

Implicit learning of the production of motor sequences will be examined during simultaneous fMRI/EEG and MEG imaging. Sensorimotor adaptation of speech production during MEG imaging will be examined during perturbing pitch or formants of auditory feedback consistently during speech production and examining the behavioral and neural correlates of the resulting across-trial adaptation responses.

Group III: Auditory feedback processing in laryngeal dystonia and voice tremor Experimental Treatment 1 Intervention

The role of auditory feedback processing on task-induced speech sensorimotor activity will be examined using MEG imaging during perturbing pitch or formants of auditory feedback, unpredictably during speech production, and examining the behavioral and neural correlates of the resulting within-trial compensation responses.

Group IV: Sensorimotor modulations of laryngeal dystonia and voice tremor with bupivacaine Active Control 1 Intervention

Topical laryngeal block (1 ml of 0.75% bupivacaine solution) will be used to modulate somatosensory feedback from the laryngeal mucosa during speech production and examine associated changes in brain activity.

Group V: Placebo effects in laryngeal dystonia and voice tremor Placebo Group 1 Intervention

1 ml of saline placebo matching to 1 ml of 0.75% bupivacaine solution will be used for a comparison with the topical laryngeal block to modulate somatosensory feedback from the laryngeal mucosa during speech production and examine associated changes in brain activity.

Who Is Running the Clinical Trial?

Massachusetts Eye and Ear Infirmary

Lead Sponsor

Trials

115

Recruited

15,000+

University of California, San Francisco

Collaborator

Trials

2,636

Recruited

19,080,000+

Published Research Related to This Trial

In a case report involving three patients with spasmodic dysphonia (SD) following head injury, multiple neurodiagnostic tests revealed significant neurological abnormalities, highlighting the potential link between head trauma and the onset of SD symptoms.

The study emphasizes the importance of considering prior head trauma in patients with SD and suggests that a single negative test for central nervous system function does not rule out the presence of neurological lesions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spasmodic dysphonia subsequent to head trauma. Finitzo, T., Pool, KD., Freeman, FJ., et al.[2019]

In a study involving 9 adults with adductor spasmodic dysphonia (ADSD), botulinum toxin (BTX) injections significantly improved speech-related brain activity, particularly in areas responsible for motor control, compared to 10 healthy volunteers.

The enhanced brain responses after BTX treatment correlated strongly with clinical improvements in speech, indicating that BTX may help the brain process sensory information more efficiently, leading to better control of laryngeal movements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alterations in CNS activity induced by botulinum toxin treatment in spasmodic dysphonia: an H215O PET study. Ali, SO., Thomassen, M., Schulz, GM., et al.[2019]

This study identified specific brain abnormalities in patients with spasmodic dysphonia using diffusion tensor imaging (DTI) and postmortem histopathology, revealing changes in the internal capsule and other brain regions associated with voice production.

The observed brain changes, including decreased axonal density and increased water diffusivity, correlate with the severity of clinical symptoms, suggesting that these abnormalities may disrupt the brain's control over voluntary voice production, contributing to the disorder's pathophysiology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Focal white matter changes in spasmodic dysphonia: a combined diffusion tensor imaging and neuropathological study. Simonyan, K., Tovar-Moll, F., Ostuni, J., et al.[2021]

In a study of 19 patients with spasmodic dysphonia, MRI revealed abnormal findings in 6 patients, including brain infarcts and demyelinating lesions, suggesting potential underlying neurological issues.

There was a weak correlation between abnormal MRI results and auditory brain stem response tests, indicating that while MRI can show associated lesions, it may not directly identify the causes of spasmodic dysphonia, highlighting the complexity of this voice disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic resonance imaging findings and correlations in spasmodic dysphonia patients. Schaefer, S., Freeman, F., Finitzo, T., et al.[2017]

Surgical treatment (lateralization thyroplasty) for spasmodic dysphonia significantly reduced or eliminated voice symptoms in all three patients studied, demonstrating its efficacy.

Post-operative brain imaging revealed a normalization of brain activity patterns, indicating that successful treatment not only alleviates vocal symptoms but also reverses abnormal central nervous system activity associated with the disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Type II thyroplasty changes cortical activation in patients with spasmodic dysphonia. Tateya, I., Omori, K., Kojima, H., et al.[2016]

Patients with adductor and abductor spasmodic dysphonia (SD) show distinct brain activation patterns, with increased activity in the primary sensorimotor cortex and decreased activity in the basal ganglia, thalamus, and cerebellum during voice tasks, indicating potential neural mechanisms underlying the disorder.

The primary somatosensory cortex appears to play a significant role in the pathophysiology of SD, as its activation correlates with symptom severity, suggesting it could be a target for future therapeutic interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abnormal activation of the primary somatosensory cortex in spasmodic dysphonia: an fMRI study. Simonyan, K., Ludlow, CL.[2021]

A study involving 11 patients with spasmodic dysphonia (SD) and healthy participants revealed that the sensorimotor cortex and thalamus are key areas affected in SD, as they showed different neural activation patterns during a sound discrimination task.

The findings suggest that sensorimotor signals correlate with the severity of SD and could serve as a potential biomarker for diagnosing the condition, with a classification accuracy of 73% between patients and healthy individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperactive sensorimotor cortex during voice perception in spasmodic dysphonia. Kanazawa, Y., Kishimoto, Y., Tateya, I., et al.[2021]

In a study of 14 patients with spasmodic dysphonia, no abnormalities were found in their auditory brainstem responses (ABR), suggesting that brainstem function may be intact in these individuals.

The SCAN-A test, which assesses central auditory processing, showed negligible positive findings, indicating that central auditory processing deficits may not be a significant feature in patients with spasmodic dysphonia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Central auditory evaluation of patients with spasmodic dysphonia. Middleton, ML., Wilson, KM., Keith, RW.[2010]

The study involved 14 patients with adductor-type spasmodic dysphonia (ADSD) and 15 control subjects, using functional MRI to assess central tactile processing and resting-state connectivity before and during the effects of botulinum neurotoxin type A (BoNT-A).

Findings revealed that ADSD patients exhibited abnormal tactile processing and increased connectivity in certain brain regions, but BoNT-A treatment did not significantly change these activation patterns, suggesting that central sensory processing abnormalities are a key feature of ADSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Altered sensory system activity and connectivity patterns in adductor spasmodic dysphonia. Mantel, T., Dresel, C., Welte, M., et al.[2021]

Citations

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

Spasmodic dysphonia subsequent to head trauma. [2019]

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

Alterations in CNS activity induced by botulinum toxin treatment in spasmodic dysphonia: an H215O PET study. [2019]

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

Focal white matter changes in spasmodic dysphonia: a combined diffusion tensor imaging and neuropathological study. [2021]

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

Magnetic resonance imaging findings and correlations in spasmodic dysphonia patients. [2017]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Type II thyroplasty changes cortical activation in patients with spasmodic dysphonia. [2016]

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

Abnormal activation of the primary somatosensory cortex in spasmodic dysphonia: an fMRI study. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Hyperactive sensorimotor cortex during voice perception in spasmodic dysphonia. [2021]

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

Central auditory evaluation of patients with spasmodic dysphonia. [2010]

9. England pubmed.ncbi.nlm.nih.gov

Altered sensory system activity and connectivity patterns in adductor spasmodic dysphonia. [2021]