Recruiting
Early Phase 1

Observational Study

Sponsor:

Massachusetts Eye and Ear Infirmary

Code:

NCT05216770

Conditions

Laryngeal Dystonia

Spasmodic Dysphonia

Tremor

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Accepted

Interventions

Brain imaging

Laryngeal sensory block with topical bupivacaine

Study Details

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

Study ID

NCT05216770

Start date

Mar 24, 2022

Status verified date

Nov, 2025

Completion date

Aug 31, 2027

Anticipated

Primary completion date

Aug 31, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Accepted

Inclusion criteria:

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

Exclusion criteria:

1. Subjects who are incapable of giving informed consent;
2. 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;
3. 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;
4. Patients with any other form of dystonia;
5. Patients who have dystonia symptoms at rest or have a presence of mirror dystonia;
6. 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;
7. 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;
8. 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;
9. 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.

Study Design

Enrollment

165 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

other: Spatial and temporal CNS pathophysiology of laryngeal dystonia and voice tremor

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

active comparator: Sensorimotor modulations of laryngeal dystonia and voice tremor with bupivacaine

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.

other: Motor learning and CNS pathophysiology of laryngeal dystonia and voice tremor

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.

placebo comparator: Placebo effects in laryngeal dystonia and voice tremor

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.

other: Auditory feedback processing in laryngeal dystonia and voice tremor

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.

Interventions

Brain imaging

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

Laryngeal sensory block with topical bupivacaine

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

Primary outcome measure

  • Functional MRI, MEG and EEG signal changes in laryngeal dystonia compared to voice tremor [ Time Frame: 5 years ]
  • Effects of sensorimotor brain modulation on voice function in laryngeal dystonia [ Time Frame: 5 years ]
  • Effects of sensorimotor brain modulation on voice function in voice tremor [ Time Frame: 5 years ]

Central Contacts and Locations

Central contacts

Locations

Massachusetts Eye and Ear and University of California San Francisco

Recruiting

Boston, Massachusetts, United States, 02114

Contacts

Principal Investigator:

Kristina Simonyan, MD, PhD

More Information

Sponsor

Massachusetts Eye and Ear Infirmary

Last update posted

Dec 2, 2025

Last verified

Nov, 2025

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Massachusetts Eye and Ear Infirmary on 2025-12-02.