Laryngeal Vibration for Spasmodic Dysphonia (SD-VTS)

• ClinicalTrials.gov Identifier: NCT03746509
• Recruitment Status: Recruiting
• First Posted: November 19, 2018
• Last Update Posted: February 11, 2022
• Sponsor: University of Minnesota
• Information provided by (Responsible Party): University of Minnesota

Study Description

Brief Summary:

The general aim of the research is to provide scientific evidence that VTS represents a non-invasive form of neuromodulation that can induce measurable improvements in the speech of SD patients. This research addresses a clinical need to develop alternative or auxiliary treatments for a rare voice disorder with limited treatment options. A successful completion of the proposed work will be an important step in advancing laryngeal VTS as a therapeutic intervention for improving the voice symptoms in SD. Specifically, the scientific yield by achieving the specific aims is threefold: First, it will elucidate the unknown neurophysiological mechanism behind laryngeal VTS by documenting the neural changes associated with VTS. Second, it will establish that VTS can improve voice quality in SD. Third, by documenting that laryngeal VTS yields long-term benefits on voice quality in SD patients, it would provide a solid basis for a clinical trial that needs to address open questions on optimal dosage and duration of VTS-based voice therapy, the magnitude of the therapeutic effect across adductor and abductor SD and its longterm efficacy.

Condition or disease	Intervention/treatment	Phase
Spasmodic Dysphonia	Device: Laryngeal Vibration (Treatment); Device: Laryngeal Vibration (Comparator)	Not Applicable

Detailed Description:

Spasmodic dysphonia (SD) is a rare voice disorder that develops spontaneously during midlife. Patients with SD typically have a strained or choked speech and report that is takes an exhausting effort to speak. The involuntary spasms of the laryngeal musculature that give rise to these symptoms almost always occur during speech. Progression is gradual in the first year and then becomes chronic for life. The cause of spasmodic dysphonia is unknown, but SD is considered to be a form of task-specific focal dystonia (FD). More women than men are affected. Current therapeutic options are limited. SD does not respond to behavioral speech therapy. It is treated primarily with Botulinum toxin injections (Botox), which provides temporary symptom relief to some, but is not well tolerated by all SD patients. At present, there is no cure for SD.

There is convergent evidence that FD is associated with kinaesthetic deficits that are also manifest in non-dystonic musculature indicating that while the motor symptoms of dystonia are focal, the associated somatosensory deficit is general. Recent work from our group (NIH 1R21DC011841) confirmed upper limb proprioceptive deficits in SD demonstrating that an underlying somatosensory deficit is also a feature of SD. In our assessment this finding opens an avenue for a missing behavioral treatment for SD. Specifically, the investigators suggest that vibro-tactile stimulation (VTS) could be the suitable tool, given that it is known to alter afferent signals from the vibrated mechanoreceptors in muscles and skin. The approach seeks to show that VTS represents a non-invasive form of neuromodulation that induces measurable improvements in the speech of SD patients. Given that SD, like other FDs, is associated with abnormally increased cortical excitation and heightened levels of neuronal synchronization, the investigators put forward that VTS can reduce sensorimotor cortical excitation in SD by desynchronizing motor cortical neuron activity as has been shown in cervical dystonia. Technically, newly available light-weight, wearable low-voltage vibrators offer, for the first time, the possibility to apply laryngeal VTS outside a controlled laboratory environment, which would be imperative for the technology to be clinically useful. In general, one needs to demonstrate that a) VTS induces measurable improvements in voice quality, b) that it induces measurable changes in somatosensory and motor cortical activation that would provide insight into the underlying neural mechanism of its potential effectiveness. Thus, the proposal has the following specific aims:

1. Demonstrate that a one-time, prolonged application of VTS produces acute improvements in SD voice quality that are retained up to 60 minutes past cessation of VTS. A pre- and post-training comparison showing significant voice improvements in the SD group as measured by self-report (Effort Scale), clinical assessment (Consensus Auditory-Perceptual Evaluation of Voice - CAPE-V), as the reduction in the number of voice breaks and determining cepstral peak prominence will realize this goal. The investigators' preliminary data show that VTS induces improvements in voice quality in SD patients as measured by these markers.
2. Demonstrate that repeated prolonged VTS produces long lasting improvements in SD voice quality that are retained for up to 3 months. SD patients will participate in an 8-week in-home VTS training program. After randomization to either a treatment or sham group (ineffective low frequency VTS), patients will start in low or high intensity training group (1 vs. 3 sessions/wk) and cross-over after 4 weeks. Showing that significant long-term voice improvements in the VTS treatment group as assessed by objective measures of voice/speech production (see aim 1) will persist over a period of 11 weeks will realize this goal.
3. Demonstrate that the application of VTS induces acute desynchronization of cortical activity in SD, which would provide neurophysiological evidence on the assumed effectiveness of VTS. Verifying that VTS is associated with short-latency characteristic changes in somatosensory and motor cortical processing as measured by electroencephalography (EEG) and documenting that these changes indicate decreased alpha and beta-band activity in sensorimotor cortical areas will achieve this goal. The investigators' preliminary data show that VTS suppresses low frequency neural activity at the somatosensory and motor cortices in healthy and SD participants. Obtaining longitudinal EEG data during VTS training (aim 2), will allow the investigators to monitor long-term changes in cortical activation due to laryngeal VTS and to associate them with changes in voice quality.

Impact. This is the first systematic study on the effect of VTS on SD voice symptoms. The proposal aligns with PA-14-236 (Advancing Research in Voice Disorders) with its emphasis on understanding voice disorders and improving diagnosis and treatment. If successful, the work of the proposal would lay the scientific foundation for a clinical trial to examine the usefulness of the approach in a larger patient sample. It would document the sensorimotor cortical activation patterns associated with SD and the longitudinal changes in cortical responses to VTS. It would promote development of wearable, user-programmable medical devices that could apply VTS while monitoring its effect on voice production in real-time. Ultimately, VTS would enlarge the available therapeutic arsenal by either augmenting existing Botox therapy or becoming an alternative intervention option for patients who do not tolerate Botox injections.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Laryngeal Vibration as a Non-invasive Treatment for Spasmodic Dysphonia
• Actual Study Start Date: April 2, 2019
• Estimated Primary Completion Date: July 2022
• Estimated Study Completion Date: July 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Low-High Treatment; Participants in the low-high treatment group will receive Laryngeal Vibration (Treatment) at 100Hz frequency once a week for a duration of 4 weeks (low intensity). Then they will switch and receive laryngeal vibration at 100Hz frequency every second day of the week (high intensity) for a duration of 4 weeks.	Device: Laryngeal Vibration (Treatment); The strength of the vibration is similar to the vibration experienced from vibrating cell phones or gaming joysticks. Vibro-tactile stimulation at the applied frequency and amplitude is not known to cause pain or tissue damage. The participant may feel a mild tingling or vibrating sensation. Preliminary testing on healthy human subjects showed that at the given vibration parameters no adverse reactions occur.
Experimental: High-Low Treatment; Participants in the high-low treatment group will receive Laryngeal Vibration (Treatment) at 100Hz frequency every second day of the week for a duration of 4 weeks (high intensity). Then they will switch and receive laryngeal vibration at 100Hz frequency once a week for a duration of 4 weeks (low intensity).	Device: Laryngeal Vibration (Treatment); The strength of the vibration is similar to the vibration experienced from vibrating cell phones or gaming joysticks. Vibro-tactile stimulation at the applied frequency and amplitude is not known to cause pain or tissue damage. The participant may feel a mild tingling or vibrating sensation. Preliminary testing on healthy human subjects showed that at the given vibration parameters no adverse reactions occur.
Active Comparator: Low-High Comparator; Participants in the low-high comparator group will receive Laryngeal Vibration (Comparator) at 5Hz frequency once a week for a duration of 4 weeks (low intensity). Then they will switch and receive laryngeal vibration at 5Hz frequency every second day of the week (high intensity) for a duration of 4 weeks.	Device: Laryngeal Vibration (Comparator); The strength of the vibration is similar to the vibration experienced from vibrating cell phones or gaming joysticks. Vibro-tactile stimulation at the applied frequency and amplitude is not known to cause pain or tissue damage. The participant may feel a mild tingling or vibrating sensation. Preliminary testing on healthy human subjects showed that at the given vibration parameters no adverse reactions occur.
Active Comparator: High-Low Comparator; Participants in the high-low comparator group will receive Laryngeal Vibration (Comparator) at 5Hz frequency every second day of the week for a duration of 4 weeks (high intensity). Then they will switch and receive laryngeal vibration at 5Hz frequency once a week for a duration of 4 weeks (low intensity).	Device: Laryngeal Vibration (Comparator); The strength of the vibration is similar to the vibration experienced from vibrating cell phones or gaming joysticks. Vibro-tactile stimulation at the applied frequency and amplitude is not known to cause pain or tissue damage. The participant may feel a mild tingling or vibrating sensation. Preliminary testing on healthy human subjects showed that at the given vibration parameters no adverse reactions occur.

Outcome Measures

Primary Outcome Measures :

1. Voice assessment 1 (baseline) [ Time Frame: Testing performed in lab at Week 1 ]
   To assess voice quality, participants will perform a series of voice production tasks in lab. Voice production before, during, and after the vibration will be recorded via a microphone for subsequent acoustic analysis on voice quality by speech analysis experts.
2. Voice assessment to measure change from baseline [ Time Frame: Testing performed in lab at Week 6 ]
   To assess voice quality, participants will perform a series of voice production tasks in lab. Voice production before, during, and after the vibration will be recorded via a microphone for subsequent acoustic analysis on voice quality by speech analysis experts.
3. Final voice assessment to measure change from baseline [ Time Frame: Testing performed in lab at Week 11 ]
   To assess voice quality, participants will perform a series of voice production tasks in lab. Voice production before, during, and after the vibration will be recorded via a microphone for subsequent acoustic analysis on voice quality by speech analysis experts.

Secondary Outcome Measures :

1. Measuring of cortical activity using electroencephalography (EEG) (baseline) [ Time Frame: Testing performed in lab at Week 1 ]
   Cortical activity before, during, and after the vibration will be recorded via a a 64-channel EEG system at a sampling frequency of 512 Hz.
2. Measuring of cortical activity using electroencephalography (EEG) to measure change from baseline [ Time Frame: Testing performed in lab at Week 6 ]
   Cortical activity before, during, and after the vibration will be recorded via a a 64-channel EEG system at a sampling frequency of 512 Hz.
3. Final measuring of cortical activity using electroencephalography (EEG) to measure change from baseline [ Time Frame: Testing performed in lab at Week 11 ]
   Cortical activity before, during, and after the vibration will be recorded via a a 64-channel EEG system at a sampling frequency of 512 Hz.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• diagnosis of adductor SD for a minimum of 6 months with documented symptom relief after botox injection

Exclusion Criteria:

• abductor SD
• patients with other voice disorders such as muscle tension dysphonia that share some of the symptomology with SD

Contacts and Locations

Contacts

Contact: Juergen Konczak, PhD; 612-624-4370; jkonczak@umn.edu

Contact: Divya Bhaskaran, PhD; 612-625-3313; bhas0021@umn.edu

Locations

United States, Minnesota

University of Minnesota; Recruiting

Minneapolis, Minnesota, United States, 55455

Contact: Divya Bhaskaran, PhD 612-625-3313 bhas0021@umn.edu

Contact: Naveen Elangovan, Ph.D. 612-625-3313 naveen@umn.edu

Principal Investigator: Juergen Konczak, PhD

Sponsors and Collaborators

University of Minnesota

Investigators

• Principal Investigator: Juergen Konczak, PhD; University of Minnesota

More Information

• Responsible Party: University of Minnesota
• ClinicalTrials.gov Identifier: NCT03746509
• Other Study ID Numbers: STUDY00004618
• First Posted: November 19, 2018
• Last Update Posted: February 11, 2022
• Last Verified: February 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Minnesota:

Dystonia; Spasmodic dysphonia; Laryngeal dystonia

Additional relevant MeSH terms:

Dysphonia; Hoarseness; Voice Disorders; Laryngeal Diseases; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Neurologic Manifestations; Nervous System Diseases; Respiration Disorders; Signs and Symptoms, Respiratory