Back to resultsrTMS in Spasmodic Dysphonia
Primary Purpose
Spasmodic Dysphonia, Laryngeal Dystonia
Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
1Hz repetitive transcranial magnetic stimulation (rTMS)
Sponsored by
About this trial
This is an interventional basic science trial for Spasmodic Dysphonia focused on measuring Repetitive transcranial magnetic stimulation (rTMS), Spasmodic dysphonia, Dystonia
Eligibility Criteria
Inclusion Criteria:
Primary inclusion for spasmodic dysphonia:
- Diagnosis of adductor spasmodic dysphonia
- Symptoms at worst severity if receiving regular botulinum injections
Primary inclusion for healthy participants (controls):
- Absence of vocal fold pathology
Exclusion Criteria:
Primary exclusion for participants with spasmodic dysphonia:
- Other forms of dystonia
- Vocal fold pathology or paralysis
- Diagnosis of voice tremor
- Laryngeal surgery
- Laryngeal cancer or neurological condition other than dystonia
- Contraindication to TMS
- Medications with effect on central nervous system
- Inability to complete tasks associated with study
- Adult lacking ability to consent
Primary exclusion for healthy participants (controls):
- Any health condition or disability that would interfere with participation
- Contraindications to TMS
- Medications with effect on central nervous system
- 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.
- Pregnancy
- Bipolar disorder
- Epilepsy or history of seizure episodes in the past two years
- Vascular, traumatic, tumoral, infectious, or metabolic lesion of the brain, even without history of seizure, and without anticonvulsant medication
- Use of medications that potentially lower seizure threshold
- Severe or recent heart disease
Sites / Locations
- Noninvasive Neuromodulation Laboratory
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Spasmodic Dysphonia
Healthy control
Arm Description
1Hz repetitive transcranial magnetic stimulation (rTMS)
Healthy adults 1Hz repetitive transcranial magnetic stimulation (rTMS)
Outcomes
Primary Outcome Measures
Adverse Response to rTMS
Count of participants who experience and adverse response to rTMS treatment.
Change in Duration of Cortical Silent Period (CSP)
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.
Secondary Outcome Measures
Change in Number of Voice Breaks
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.
Change in Voice Quality (Overall Severity) With the Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V)
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.
Change in Cepstral Peak Prominence Smoothed (CPPS)
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.
Full Information
NCT ID
NCT02957942
First Posted
October 26, 2016
Last Updated
September 28, 2020
Sponsor
University of Minnesota
1. Study Identification
Unique Protocol Identification Number
NCT02957942
Brief Title
rTMS in Spasmodic Dysphonia
Official Title
Repetitive Transcranial Magnetic Stimulation in Spasmodic Dysphonia
Study Type
Interventional
2. Study Status
Record Verification Date
September 2020
Overall Recruitment Status
Completed
Study Start Date
January 2017 (Actual)
Primary Completion Date
December 2018 (Actual)
Study Completion Date
December 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Minnesota
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Spasmodic Dysphonia, Laryngeal Dystonia
Keywords
Repetitive transcranial magnetic stimulation (rTMS), Spasmodic dysphonia, Dystonia
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Spasmodic Dysphonia
Arm Type
Experimental
Arm Description
1Hz repetitive transcranial magnetic stimulation (rTMS)
Arm Title
Healthy control
Arm Type
Active Comparator
Arm Description
Healthy adults 1Hz repetitive transcranial magnetic stimulation (rTMS)
Intervention Type
Device
Intervention Name(s)
1Hz repetitive transcranial magnetic stimulation (rTMS)
Intervention Description
1 session of low-frequency rTMS (1Hz, 1200 pulses, 20 minutes)
Primary Outcome Measure Information:
Title
Adverse Response to rTMS
Description
Count of participants who experience and adverse response to rTMS treatment.
Time Frame
2.5 hours
Title
Change in Duration of Cortical Silent Period (CSP)
Description
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.
Time Frame
baseline and 2.5 hours
Secondary Outcome Measure Information:
Title
Change in Number of Voice Breaks
Description
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.
Time Frame
baseline and 2.5 hours
Title
Change in Voice Quality (Overall Severity) With the Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V)
Description
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.
Time Frame
baseline and 2.5 hours
Title
Change in Cepstral Peak Prominence Smoothed (CPPS)
Description
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.
Time Frame
baseline and 2.5 hours
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Primary inclusion for spasmodic dysphonia:
Diagnosis of adductor spasmodic dysphonia
Symptoms at worst severity if receiving regular botulinum injections
Primary inclusion for healthy participants (controls):
Absence of vocal fold pathology
Exclusion Criteria:
Primary exclusion for participants with spasmodic dysphonia:
Other forms of dystonia
Vocal fold pathology or paralysis
Diagnosis of voice tremor
Laryngeal surgery
Laryngeal cancer or neurological condition other than dystonia
Contraindication to TMS
Medications with effect on central nervous system
Inability to complete tasks associated with study
Adult lacking ability to consent
Primary exclusion for healthy participants (controls):
Any health condition or disability that would interfere with participation
Contraindications to TMS
Medications with effect on central nervous system
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.
Pregnancy
Bipolar disorder
Epilepsy or history of seizure episodes in the past two years
Vascular, traumatic, tumoral, infectious, or metabolic lesion of the brain, even without history of seizure, and without anticonvulsant medication
Use of medications that potentially lower seizure threshold
Severe or recent heart disease
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mo Chen, PhD
Organizational Affiliation
University of Minnesota
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Teresa J Kimberley, PhD, PT
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Noninvasive Neuromodulation Laboratory
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
19833552
Citation
Rossi S, Hallett M, Rossini PM, Pascual-Leone A; Safety of TMS Consensus Group. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol. 2009 Dec;120(12):2008-2039. doi: 10.1016/j.clinph.2009.08.016. Epub 2009 Oct 14.
Results Reference
background
PubMed Identifier
25797650
Citation
Rossini PM, Burke D, Chen R, Cohen LG, Daskalakis Z, Di Iorio R, Di Lazzaro V, Ferreri F, Fitzgerald PB, George MS, Hallett M, Lefaucheur JP, Langguth B, Matsumoto H, Miniussi C, Nitsche MA, Pascual-Leone A, Paulus W, Rossi S, Rothwell JC, Siebner HR, Ugawa Y, Walsh V, Ziemann U. Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves: Basic principles and procedures for routine clinical and research application. An updated report from an I.F.C.N. Committee. Clin Neurophysiol. 2015 Jun;126(6):1071-1107. doi: 10.1016/j.clinph.2015.02.001. Epub 2015 Feb 10.
Results Reference
background
PubMed Identifier
28231250
Citation
Summers RL, Chen M, Kimberley TJ. Corticospinal excitability measurements using transcranial magnetic stimulation are valid with intramuscular electromyography. PLoS One. 2017 Feb 23;12(2):e0172152. doi: 10.1371/journal.pone.0172152. eCollection 2017.
Results Reference
background
PubMed Identifier
26217209
Citation
Kimberley TJ, Schmidt RL, Chen M, Dykstra DD, Buetefisch CM. Mixed effectiveness of rTMS and retraining in the treatment of focal hand dystonia. Front Hum Neurosci. 2015 Jul 9;9:385. doi: 10.3389/fnhum.2015.00385. eCollection 2015.
Results Reference
background
PubMed Identifier
28326007
Citation
Chen M, Summers RL, Goding GS, Samargia S, Ludlow CL, Prudente CN, Kimberley TJ. Evaluation of the Cortical Silent Period of the Laryngeal Motor Cortex in Healthy Individuals. Front Neurosci. 2017 Mar 7;11:88. doi: 10.3389/fnins.2017.00088. eCollection 2017.
Results Reference
background
PubMed Identifier
34859288
Citation
Prudente CN, Chen M, Stipancic KL, Marks KL, Samargia-Grivette S, Goding GS, Green JR, Kimberley TJ. Effects of low-frequency repetitive transcranial magnetic stimulation in adductor laryngeal dystonia: a safety, feasibility, and pilot study. Exp Brain Res. 2022 Feb;240(2):561-574. doi: 10.1007/s00221-021-06277-4. Epub 2021 Dec 2.
Results Reference
derived
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rTMS in Spasmodic Dysphonia
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