Effects of Neuromodulation in Laryngeal Dystonia
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age21-85
SponsorMGH Institute of Health Professions
About this trial
Laryngeal dystonia (LD) causes excessive vocal fold abduction (opening) or adduction (closing) leading to decreased voice quality, job prospects, self-worth and quality of life. Individuals with LD often experience episodic breathy voice, decreased ability to sustain vocal fold vibration, frequent pitch breaks and in some cases, vocal tremor. While neuroimaging investigations have uncovered both cortical organization and regional connectivity differences in structures in parietal, primary somatosensory and premotor cortices of those with LD, there remains a lack of understanding regarding how the brains of those with LD function to produce phonation and how these might differ from those without LD. Intervention options for people with LD are limited to general voice therapy techniques and Botulinum Toxin (Botox) injections to the posterior cricoarytenoid (PCA) and/or TA (thyroarytenoid) often bilaterally, to alleviate muscle spasms in the vocal folds. However, the effects of injections are short-lived, uncomfortable, and variable. To address this gap, the aim of this study is to investigate the effectiveness of repetitive transcranial magnetic stimulation (rTMS), a non-invasive neuromodulation technique, in assessing cortical excitability and inhibition of laryngeal musculature. Previous work conducted by the investigator has demonstrated decreased intracortical inhibition in those with adductor laryngeal dystonia (AdLD) compared to healthy controls. The investigators anticipate similar findings in individuals with with other forms of LD, where decreased cortical inhibition will likely be noted in the laryngeal motor cortex. Further, following low frequency (inhibitory) rTMS to the laryngeal motor brain area, it is anticipated that there will be a decrease in overactivation of the TA muscle. To test this hypothesis, a proof-of-concept, randomized study to down-regulate cortical motor signal to laryngeal muscles will be compared to those receiving an equal dose of sham rTMS. Previous research conducted by the investigator found that a single session of the proposed therapy produced positive phonatory changes in individuals with AdLD and justifies exploration in LD.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Age range is 21-85 years
Diagnosis of Laryngeal Dystonia (LD)
Subject is able to give informed consent
Symptoms at worst severity if receiving botulinum toxin injections
Disqualifiers
Other forms of dystonia
Vocal fold pathology or paralysis
Essential tremor
Laryngeal cancer or other neurologic conditions with medications affecting the central nervous system
Trial design
Design model
Crossover
Treatments tested in this trial
repetitive transcranial magnetic stimulation (rTMS)
DeviceRepetitive transcranial magnetic stimulation used to regulate the contribution of the laryngeal motor cortex to voice production and laryngeal motor muscle activation.
sham rTMS
DeviceRepetitive transcranial magnetic stimulation used to a cortical area not associated with change in outcomes at an intensity substantially lower than that of the established threshold.
Treatment groups
25 Participants
are divided into 2 treatment groupsGroup A: repetitive transcranial magnetic stimulation (rTMS)Active comparator 1 intervention
Group B: Sham rTMSSham comparator 1 intervention
Trial outcomes
Primary outcomes
1
Change in Objective Assessment of Phonatory Function
Participants will produce sustained /ah/ vowels, read the rainbow passage and engage in freeform conversation. This speech will be recorded and measures of cepstral peak prominence smoothed (CPPS; range: 0-100, where higher indicates stronger voice signal and correlates highly with better voice quality).
Time frame
Day 1 (baseline), day 5 (post intervention), and Day 12 (follow up) timepoints for both arms of the study.2
Change in Cortical Excitability (intrahemispheric inhibition)
Intrahemispheric inhibition will be measured with the cortical silent period (cSP) measured in ms
Time frame
Day 1 (baseline), Day 5 (post intervention)Secondary outcomes
1
Subjective Assessment of Phonatory Function
Three speech language pathologists who specialize in voice disorders and are blinded to treatment day or group, will listen to the recorded audio sentences and sustained vowels and perform an independent overall perceptual evaluation of each participant's voice for each assessment session using the rating scales from the American Speech-Language-Hearing Association recommended Consensus Auditory Perceptual Evaluation of Voice (CAPE-V). The primary measure will be the rating for Overall Severity of dysphonia, and secondary measures will include ratings for strain, roughness, breathiness, pitch and loudness. Scores closer to 0 indicate less severity and closer to 100 indicate more severely disordered. Each judge will listen to recordings of 20% of the assessments (randomly selected) twice for purposes of estimating intra-judge reliability. Ratings from the three judges will be averaged to produce one score for each perceptual parameter.
Time frame
Day 1 (baseline), Day 5 (post intervention), and Day 12 (follow up) timepoints for both arms of the study.2
Self Ratings of Voice Effort
Self ratings of voice effort on a visual analog scale (VAS) after reading the sentences in Outcome 1. "Speaking required how much effort?" 0=minimal effort, 10= maximal effort
Time frame
Day 1 (baseline), Day 5 (post intervention), and Day 12 (follow up) timepoints for both arms of the study.3
Secondary Objective assessment of phonatory function
In addition to the CPPS (primary measure above), the voice samples will be analyzed with the following: number of phonatory breaks (range: 0-x; were few breaks indicates a better voice quality), frequency shifts (range: 0-x Hz; where a smaller shift (closer to 0) is generally indicative of better voice quality) and the number of aperiodic segments (range: 0-x; where fewer aperiodic voice segments is generally indicative of better voice quality) will be obtained from each recording. These will be analyzed and compared over time.
Time frame
Day 1 (baseline), Day 5 (post intervention), and Day 12 (follow up) timepoints for both arms of the study.Other outcomes
1
Forced choice paired assessment of phonatory function
If the primary or secondary assessments of objective or perceptual ratings of change fail to capture change in participants' voice between baseline and post intervention, a forced choice question will be posed to blinded raters to ask which paired voice sample represents the less severe sample and then perform a VAS ranking of how severe the voice sample sounds (0=minimal impairment, 10=severe impairment)
Time frame
Day 1 (baseline), Day 5 (post intervention), and Day 12 (follow up) timepoints for both arms of the study.Sponsors and contacts
Click on the lead sponsor to view all of their trials.
MGH Institute of Health Professions
Lead sponsor
National Institute on Deafness and Other Communication Disorders (NIDCD)
Collaborator
Source ClinicalTrials.gov