Understanding Disorder-specific Neural Pathophysiology in Laryngeal Dystonia and Voice Tremor

NCT05216770 | Recruiting Early Phase 1 FDA Drug

• 1 other identifier: 2021P003142
• Study Type: interventional
• Target: 165
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Laryngeal Dystonia; Spasmodic Dysphonia; Tremor

Outcome Measures

Primary Outcomes (3)

• Functional MRI, MEG and EEG signal changes in laryngeal dystonia compared to voice tremor

  Qualitative analysis of brain regions with disorder-specific increases and decreases of spatial (functional MRI) and temporal (MEG and EEG) signals will be determined in patients with laryngeal dystonia compared to patients with voice tremor

  5 years

• Effects of sensorimotor brain modulation on voice function in laryngeal dystonia

  Quantitative measures of symptoms will be determined using Burk-Fahn-Marsden Dystonia Rating Scale where higher score means a worse outcome, following sensorimotor feedback modulation in patients with laryngeal dystonia

  5 years

• Effects of sensorimotor brain modulation on voice function in voice tremor

  Quantitative measures of symptoms will be determined using Fahn-Tolosa-Marin Rating Scale where higher score means a worse outcome, following sensorimotor feedback modulation in patients with voice tremor

  5 years

Study Arms (5)

Spatial and temporal CNS pathophysiology of laryngeal dystonia and voice tremor

OTHER

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

Other: Brain imaging

Sensorimotor modulations of laryngeal dystonia and voice tremor with bupivacaine

ACTIVE COMPARATOR

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.

Drug: Laryngeal sensory block with topical bupivacaine

Motor learning and CNS pathophysiology of laryngeal dystonia and voice tremor

OTHER

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.

Other: Brain imaging

Placebo effects in laryngeal dystonia and voice tremor

PLACEBO COMPARATOR

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.

Auditory feedback processing in laryngeal dystonia and voice tremor

OTHER

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.

Other: Brain imaging

Interventions

Brain imaging OTHER

Brain images will be conducted with function MRI, magnetoencephalography (MEG), and electroencephalography (EEG) to identify disorder-specific neural markers

Auditory feedback processing in laryngeal dystonia and voice tremor; Motor learning and CNS pathophysiology of laryngeal dystonia and voice tremor; Spatial and temporal CNS pathophysiology of laryngeal dystonia and voice tremor

Laryngeal sensory block with topical bupivacaine DRUG

Laryngeal sensory block with bupivacaine will be used to modulate sensory feedback from vocal fold mucosa and examine the impact of sensory feedback on abnormal neural activity in LD and VT

Sensorimotor modulations of laryngeal dystonia and voice tremor with bupivacaine

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females of diverse racial and ethnic background;
• Age 18-80 years;
• Native English speakers;
• Right-handed;
• Normal cognitive status;
• Patients will have laryngeal dystonia or voice tremor;
• Healthy controls will be healthy individuals without neurological, psychiatric or otolaryngological problems.

You may not qualify if:

• Subjects who are incapable of giving informed consent;
• Pregnant or breastfeeding women until a time when they are no longer pregnant or breastfeeding. All women of childbearing potential will have a urine pregnancy test performed before MRI, which must be negative for participation in the imaging studies;
• Subjects with a past or present medical history of (a) neurological problems, such as stroke, movement disorders (other than specified LD and VT in the patient groups), brain tumors, traumatic brain injury with loss of consciousness, ataxias, myopathies, myasthenia gravis, demyelinating diseases; (b) psychiatric problems, such as schizophrenia, bipolar depression, obsessive-compulsive disorder, alcoholism, drug dependence; (c) laryngeal problems, such as vocal fold paralysis, paresis, vocal fold nodules and polyps, carcinoma, chronic laryngitis;
• Patients with any other form of dystonia;
• Patients who have dystonia symptoms at rest or have a presence of mirror dystonia;
• Patients who are not symptomatic due to treatment with botulinum toxin injections into the affected muscles. The duration of positive effects of botulinum toxin varies from patient to patient but lasts, on average, for 3-4 months. All patients will be evaluated to ensure that they are fully symptomatic and are at least 3 months post-injection before participation;
• To avoid the confounding effect of centrally acting drugs, all study participants will be questioned about any prescribed or over-the-counter medications as part of their initial screening. Those patients who receive medication(s) affecting the central nervous system will be excluded;
• Patients will be asked whether they have undergone any head or neck surgery, which resulted in changes in regional anatomy or innervation. Because brain or laryngeal surgery may potentially lead to brain structure and function re-organization, all patients with such a history will be excluded;
• Subjects who have certain tattoos and ferromagnetic objects in their bodies (e.g., implanted stimulators, surgical clips, prosthesis, artificial heart valve) that cannot be removed for MRI studies.

Sponsors & Collaborators

• Massachusetts Eye and Ear Infirmary: lead
• University of California, San Francisco: collaborator

Study Sites (1)

Massachusetts Eye and Ear and University of California San Francisco

Boston, Massachusetts, 02114, United States

RECRUITING

MeSH Terms

Conditions

Dysphonia; Tremor

Interventions

Neuroimaging; Bupivacaine

Condition Hierarchy (Ancestors)

Voice Disorders; Laryngeal Diseases; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Dyskinesias

Intervention Hierarchy (Ancestors)

Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Neurological; Investigative Techniques; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Study Officials

• Kristina Simonyan, MD, PhD

  Professor of Otolaryngology - Head and Neck Surgery

  STUDY DIRECTOR

Central Study Contacts

Kristina Simonyan, MD, PhD

CONTACT

617-573-6016; simonyan_lab@meei.harvard.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Otolaryngology - Head and Neck Surgery

Model Details: Only one of three arms includes Intervention. The other two arms are Observational. The Interventional arm has a parallel study model where patients with laryngeal dystonia and voice tremor will be assigned to laryngeal sensory block in parallel. Allocation will be non-randomized.

Study Record Dates

• First Submitted: November 27, 2021
• First Posted: February 1, 2022
• Study Start: March 24, 2022
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): August 31, 2027
• Last Updated: December 2, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)