rTMS in Spasmodic Dysphonia

September 28, 2020 updated by: University of Minnesota

Repetitive Transcranial Magnetic Stimulation in Spasmodic Dysphonia

Focal dystonia is a neurological movement disorder characterized by excessive involuntary muscle contractions of any body part. Spasmodic dysphonia (SD) is a type of focal dystonia characterized by excessive contraction of intrinsic muscles in the larynx, leading to difficulty in speaking and affecting effective communication. The cause of SD is unknown and there are no treatments that produce long-term benefits. Previous studies have suggested that SD and other focal dystonias are associated with decreased inhibition in sensorimotor areas in the brain. However, no studies have investigated the effects of modulating excitability of the laryngeal motor cortex in healthy individuals or SD. The goal of this pilot project is to determine if brain excitability of the laryngeal motor cortex can be changed with low-frequency inhibitory repetitive transcranial magnetic stimulation (rTMS) in individuals with SD and healthy controls. Considering that rTMS at low frequencies (≤1 Hz) produces lasting inhibition in the brain, and that SD is associated with decreased cortical inhibition, the purpose of this pilot study is to determine safety, feasibility and response to 1Hz rTMS to the laryngeal motor cortex in individuals with SD and healthy people. The results will help understand changes associated with the disorder, as well as contribute to the development of future clinical interventions for SD.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Noninvasive Neuromodulation Laboratory

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Primary inclusion for spasmodic dysphonia:

    1. Diagnosis of adductor spasmodic dysphonia
    2. Symptoms at worst severity if receiving regular botulinum injections

  • Primary inclusion for healthy participants (controls):

    1. Absence of vocal fold pathology

Exclusion Criteria:

  • Primary exclusion for participants with spasmodic dysphonia:

    1. Other forms of dystonia
    2. Vocal fold pathology or paralysis
    3. Diagnosis of voice tremor
    4. Laryngeal surgery
    5. Laryngeal cancer or neurological condition other than dystonia
    6. Contraindication to TMS
    7. Medications with effect on central nervous system
    8. Inability to complete tasks associated with study
    9. Adult lacking ability to consent

  • Primary exclusion for healthy participants (controls):

    1. Any health condition or disability that would interfere with participation
    2. Contraindications to TMS
    3. Medications with effect on central nervous system
    4. Adult lacking ability to consent

TMS contraindications:

  • The only absolute contraindication to TMS/rTMS is the presence of metallic hardware in close contact to the discharging coil (such as cochlear implants, deep brain stimulator, or medication pumps). In such instances there is a risk of inducing malfunctioning of the implanted devices.

  • Conditions classified as of increased or uncertain risk are listed below (Rossi et al., 2009; Rossini et al., 2015). Persons under those circumstances will be excluded from the study.

    1. Pregnancy
    2. Bipolar disorder
    3. Epilepsy or history of seizure episodes in the past two years
    4. Vascular, traumatic, tumoral, infectious, or metabolic lesion of the brain, even without history of seizure, and without anticonvulsant medication
    5. Use of medications that potentially lower seizure threshold
    6. Severe or recent heart disease

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: BASIC_SCIENCE
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Spasmodic Dysphonia
1Hz repetitive transcranial magnetic stimulation (rTMS)
Device: 1Hz repetitive transcranial magnetic stimulation (rTMS)
1 session of low-frequency rTMS (1Hz, 1200 pulses, 20 minutes)
Active Comparator: Healthy control
Healthy adults 1Hz repetitive transcranial magnetic stimulation (rTMS)
Device: 1Hz repetitive transcranial magnetic stimulation (rTMS)
1 session of low-frequency rTMS (1Hz, 1200 pulses, 20 minutes)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse Response to rTMS
Time Frame: 2.5 hours
Count of participants who experience and adverse response to rTMS treatment.
2.5 hours
Change in Duration of Cortical Silent Period (CSP)
Time Frame: baseline and 2.5 hours
The change from baseline in CSP duration will be reported. The CSP is an interruption of voluntary muscle contraction after single pulse transcranial stimulation. The duration of the period of silent muscle activity will be measured to test the effects of rTMS intervention. There is no known clinical relevance for this outcome measure.
baseline and 2.5 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Number of Voice Breaks
Time Frame: baseline and 2.5 hours
Changes from baseline in the number of voice breaks during speech will be reported. Voice breaks will be measured by asking subjects to repeat 10 sentences. The frequency of voice breaks in the recorded 10 sentences will be counted.
baseline and 2.5 hours
Change in Voice Quality (Overall Severity) With the Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V)
Time Frame: baseline and 2.5 hours
CAPE-V (overall severity) testing before and after rTMS consisted of the repetition of six sentences and two sustained vowels (/a/;/i/). A short sample of spontaneous speech (approximately 60s) was also collected for qualitative analysis of voice. The CAPE-V ratings were completed by three assessors who were blinded to group and pre/post-test. The assessors listened to the voice recordings for each participant and rated them for all six parameters listed above from 0 to 100, with higher values indicating worse severity. Ratings for each voice parameter were then averaged across the three assessors. We chose to analyze the change in the CAPE-V parameter for "Overall Severity" to represent an overall assessment of voice quality from pre- to post-rTMS (Post Score - Pre Score) as it had the greatest likelihood of detecting any small changes that may be perceived.
baseline and 2.5 hours
Change in Cepstral Peak Prominence Smoothed (CPPS)
Time Frame: baseline and 2.5 hours
Quantitative assessment of voice quality was completed with acoustic analysis of each participant's production of the ten sentences from the Spasmodic Dysphonia Attribute Inventory (SDAI). A custom script in Praat (Boersma & Weenink, 2018) was used to calculate cepstral peak prominence smoothed (CPPS) for each sentence production. CPPS is a relatively new measure that reflects vocal fold periodicity and noise components in the vocal spectrum. CPPS has been found to be correlated with perceived severity of voice symptoms and higher CPPS values represent a more normal vocal quality. CPPS values (in dB) were averaged across the ten sentences of the SDAI to derive an average CPPS for each participant before and after rTMS. Change for each participant was calculated as the average CPPS at post-rTMS minus average CPPS at pre-rTMS. The values for each group were then averaged to report the average change in CPPS for Controls and Spasmodic Dysphonia.
baseline and 2.5 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Minnesota

Investigators

  • Principal Investigator: Mo Chen, PhD, University of Minnesota
  • Principal Investigator: Teresa J Kimberley, PhD, PT, Massachusetts General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2017

Primary Completion (Actual)

December 1, 2018

Study Completion (Actual)

December 1, 2018

Study Registration Dates

First Submitted

October 26, 2016

First Submitted That Met QC Criteria

November 3, 2016

First Posted (Estimate)

November 8, 2016

Study Record Updates

Last Update Posted (Actual)

October 1, 2020

Last Update Submitted That Met QC Criteria

September 28, 2020

Last Verified

September 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PSYCH-2016-25008

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe