Laryngeal Vibration for Spasmodic Dysphonia
Condition: Spasmodic Dysphonia
MeSH terms: Dysphonia; Hoarseness
Study type: Interventional

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.
    

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.
    

Intervention name(s): Laryngeal Vibration (Treatment); Laryngeal Vibration (Comparator)
Intervention type(s): Device; Device
Intervention description(s): 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.; 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.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: Dystonia; Spasmodic dysphonia; Laryngeal dystonia