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Laryngeal Vibration for Spasmodic Dysphonia

Laryngeal Vibration as a Non-invasive Treatment for Spasmodic Dysphonia

Status
Completed
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT03746509
Acronym
SD-VTS
Enrollment
42
Registered
2018-11-19
Start date
2019-04-02
Completion date
2022-07-20
Last updated
2025-05-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Spasmodic Dysphonia

Keywords

Dystonia, Spasmodic dysphonia, Laryngeal dystonia

Brief summary

The general aim of the research is to provide scientific evidence that vibro-tactile stimulation (VTS) represents a non-invasive form of neuromodulation that can induce measurable improvements in the speech of people with spasmodic dysphonia (SD). 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 long term efficacy.

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.

Interventions

DEVICELaryngeal 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.

DEVICELaryngeal 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.

Sponsors

National Institute on Deafness and Other Communication Disorders (NIDCD)
CollaboratorNIH
University of Minnesota
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)

Eligibility

Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes

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

Design outcomes

Primary

MeasureTime frameDescription
Voice Assessment During First VisitTesting performed in lab at Week 1Smoothed Cepstral Peak Prominence (CPPS) is an indicator of voice quality. It is measured in decibels. CPPS was measured from the voice signals of each participant during each study visit, and relative CPPS was calculated before and after vibration was applied on the laryngeal muscles of the participants. An increase in CPPS value indicates an improvement in voice symptoms.
Final Voice AssessmentTesting performed in lab at week 11Smoothed Cepstral Peak Prominence (CPPS) which is an indicator of voice quality was measured in participants. CPPS was measured in participants during the first visit, and relative CPPS was calculated before and after vibration was applied on the laryngeal muscles of the participants.

Secondary

MeasureTime frameDescription
Measuring of Cortical Activity Using Electroencephalography (EEG) (Baseline)Testing performed in lab at Week 1Cortical activity before, during, and after the vibration will be recorded via a a 64-channel EEG system at a sampling frequency of 512 Hz.
Final Measuring of Cortical Activity Using Electroencephalography (EEG) to Measure Change From BaselineTesting performed in lab at Week 11Cortical activity before, during, and after the vibration will be recorded via a a 64-channel EEG system at a sampling frequency of 512 Hz.

Countries

United States

Participant flow

Recruitment details

Participants were recruited from Fairview Voice Clinic at the University of Minnesota and through e-mail advertisements sent by the National Spasmodic Dysphonia Association as well as social media platforms. Recruitment began in the Fall of 2018.

Participants by arm

ArmCount
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. 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.
11
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). 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.
10
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. 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.
11
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). 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.
10
Total42

Baseline characteristics

CharacteristicHigh-Low TreatmentLow-High ComparatorLow-High TreatmentHigh-Low ComparatorTotal
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
6 Participants7 Participants7 Participants2 Participants22 Participants
Age, Categorical
Between 18 and 65 years
4 Participants4 Participants4 Participants8 Participants20 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants1 Participants0 Participants0 Participants1 Participants
Race (NIH/OMB)
Asian
0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Black or African American
0 Participants0 Participants0 Participants2 Participants2 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
White
10 Participants10 Participants11 Participants8 Participants39 Participants
Sex: Female, Male
Female
5 Participants7 Participants7 Participants4 Participants23 Participants
Sex: Female, Male
Male
5 Participants4 Participants4 Participants6 Participants19 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
deaths
Total, all-cause mortality
0 / 110 / 100 / 110 / 10
other
Total, other adverse events
0 / 110 / 100 / 110 / 10
serious
Total, serious adverse events
0 / 110 / 100 / 110 / 10

Outcome results

Primary

Final Voice Assessment

Smoothed Cepstral Peak Prominence (CPPS) which is an indicator of voice quality was measured in participants. CPPS was measured in participants during the first visit, and relative CPPS was calculated before and after vibration was applied on the laryngeal muscles of the participants.

Time frame: Testing performed in lab at week 11

ArmMeasureValue (MEDIAN)
Low-High TreatmentFinal Voice Assessment0.96 decibel
High-Low TreatmentFinal Voice Assessment0.55 decibel
Low-High ComparatorFinal Voice Assessment0.64 decibel
High-Low ComparatorFinal Voice Assessment0.23 decibel
Primary

Voice Assessment During First Visit

Smoothed Cepstral Peak Prominence (CPPS) is an indicator of voice quality. It is measured in decibels. CPPS was measured from the voice signals of each participant during each study visit, and relative CPPS was calculated before and after vibration was applied on the laryngeal muscles of the participants. An increase in CPPS value indicates an improvement in voice symptoms.

Time frame: Testing performed in lab at Week 1

ArmMeasureValue (MEDIAN)
Low-High TreatmentVoice Assessment During First Visit0.045 decibel
High-Low TreatmentVoice Assessment During First Visit0.17 decibel
Low-High ComparatorVoice Assessment During First Visit0.13 decibel
High-Low ComparatorVoice Assessment During First Visit-0.47 decibel
Secondary

Final Measuring of Cortical Activity Using Electroencephalography (EEG) to Measure Change From Baseline

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.

Time frame: Testing performed in lab at Week 11

Secondary

Measuring of Cortical Activity Using Electroencephalography (EEG) (Baseline)

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.

Time frame: Testing performed in lab at Week 1

Source: ClinicalTrials.gov · Data processed: Feb 6, 2026