Spasmodic DysphoniaNCT02957942
rTMS in Spasmodic Dysphonia
A study testing 1Hz repetitive transcranial magnetic stimulation (rTMS) in people with Spasmodic Dysphonia and Laryngeal Dystonia, run by University of Minnesota at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 21 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Spasmodic Dysphonia, Laryngeal Dystonia
- What is being tested?
- 1Hz repetitive transcranial magnetic stimulation (rTMS)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2017to Dec 2018
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 24Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Noninvasive Neuromodulation Laboratory
Minneapolis, Minnesota, 55455
About this study
Official title: 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.
- Conditions
- Spasmodic Dysphonia, Laryngeal Dystonia
- Being tested
- 1Hz repetitive transcranial magnetic stimulation (rTMS)
- Keywords
- Repetitive transcranial magnetic stimulation (rTMS), Spasmodic dysphonia, Dystonia
- Medical subject headings
- Dysphonia, Dystonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
1Hz repetitive transcranial magnetic stimulation (rTMS)Device
1 session of low-frequency rTMS (1Hz, 1200 pulses, 20 minutes)
| Study group | Role | What they receive |
|---|---|---|
| Spasmodic Dysphonia | Experimental | 1Hz repetitive transcranial magnetic stimulation (rTMS) Receives: Device: 1Hz repetitive transcranial magnetic stimulation (rTMS) |
| Healthy control | Active comparator | Healthy adults 1Hz repetitive transcranial magnetic stimulation (rTMS) Receives: Device: 1Hz repetitive transcranial magnetic stimulation (rTMS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Response to rTMS
Count of participants who experience and adverse response to rTMS treatment.
Measured: 2.5 hours
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.
Measured: baseline and 2.5 hours
Secondary outcomes (3)
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.
Measured: baseline and 2.5 hours
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.
Measured: baseline and 2.5 hours
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.
Measured: baseline and 2.5 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2016 (estimated)
- Study startJan 2017
- Primary completionDec 2018
- Study completionDec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Spasmodic DysphoniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mo Chen, PhD, Principal investigator, University of MinnesotaTeresa J Kimberley, PhD, PT, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02957942
- Sponsor's protocol ID
- PSYCH-2016-25008
- Status last verified
- Sep 2020
- First submitted
- 26 Oct 2016
- Last updated
- 1 Oct 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 19833552Rossini 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.
PubMed 25797650Summers 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.
PubMed 28231250Kimberley 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.
PubMed 26217209Chen 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.
PubMed 28326007Prudente 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.
PubMed 34859288
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Repetitive Transcranial Magnetic Stimulation in Spasmodic Dysphonia
- ClinicalTrials.gov ID
- NCT02957942
- Acronym / sponsor ID
- PSYCH-2016-25008
- Conditions
- Spasmodic Dysphonia, Laryngeal Dystonia
- Keywords
- Repetitive transcranial magnetic stimulation (rTMS), Spasmodic dysphonia, Dystonia
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of MinnesotaUniversity, hospital or other
- Study start
- Jan 2017 (actual)
- Primary completion
- Dec 2018 (actual)
- Study completion
- Dec 2018 (actual)
- First posted
- 8 Nov 2016 (estimated)
- Results
- Posted 1 Oct 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Spasmodic Dysphonia | Experimental | Device: 1Hz repetitive transcranial magnetic stimulation (rTMS)1Hz repetitive transcranial magnetic stimulation (rTMS) |
| Healthy control | Active comparator | Device: 1Hz repetitive transcranial magnetic stimulation (rTMS)Healthy adults 1Hz repetitive transcranial magnetic stimulation (rTMS) |
Who may qualify
- Ages
- 21 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Primary inclusion for spasmodic dysphonia:
- Primary inclusion for healthy participants (controls):
Key exclusion criteria (24 listed)
- Primary exclusion for participants with spasmodic dysphonia:
- Primary exclusion for healthy participants (controls):
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 1Hz repetitive transcranial magnetic stimulation (rTMS)1 session of low-frequency rTMS (1Hz, 1200 pulses, 20 minutes) | Device | Healthy control, Spasmodic Dysphonia |
Primary outcome
Adverse Response to rTMS
Time frame: 2.5 hours
Count of participants who experience and adverse response to rTMS treatment.
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.
3 secondary outcomes
Change in Number of Voice Breaks
Time frame: 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
Change in Cepstral Peak Prominence Smoothed (CPPS)
Time frame: baseline and 2.5 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 19833552Rossi 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.
- Background: PubMed 25797650Rossini 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.
- Background: PubMed 28231250Summers 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.
- Background: PubMed 26217209Kimberley 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.
- Background: PubMed 28326007Chen 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.
- Derived from this study: PubMed 34859288Prudente 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.
- Individual participant dataSharing planned: No
Related trials for Spasmodic Dysphonia
Not yet recruiting
EMG-Guided Versus Endoscopic-Catheter Botulinum Toxin Injection for Spasmodic Dysphonia
Spasmodic Dysphonia
Not yet recruiting
Assessment of Laryngopharyngeal Sensation: Cancer Survivor Cohort
Presbylarynx, Aspiration
RecruitingObservational study
Deep Brain Stimulation for Laryngeal Dystonia: From Mechanism to Optimal Application
Laryngeal Dystonia, Adductor Spastic Dysphonia of Dystonia
Not yet recruiting
Transcranial Magnetic Stimulation in Laryngeal Dystonia
Laryngeal Dystonia, Spasmodic Dysphonia
Not yet recruitingPhase 1
Extended-release Sodium Oxybate (Lumryz) in Spasmodic Dysphonia and Voice Tremor
Spasmodic Dysphonia, Laryngeal Dystonia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mo Chen, PhD principal investigator
University of Minnesota
Teresa J Kimberley, PhD, PT principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing 1Hz repetitive transcranial magnetic stimulation (rTMS) in people with Spasmodic Dysphonia and Laryngeal Dystonia, run by University of Minnesota at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Oct 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse Response to rTMS (time frame: 2.5 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02957942, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2020.