Clinical trial NCT02957942: rTMS in Spasmodic Dysphonia
Official title: Repetitive Transcranial Magnetic Stimulation in Spasmodic Dysphonia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Spasmodic Dysphonia
Laryngeal Dystonia
Keywords: Repetitive transcranial magnetic stimulation (rTMS)
Spasmodic dysphonia
Dystonia
Lead sponsor: University of Minnesota
Sponsor class: OTHER
First posted: 2016-11-08
Enrollment: 20
Sex: ALL
Minimum age (years): 21
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: Adverse Response to rTMS
timeFrame: 2.5 hours
measure: Change in Duration of Cortical Silent Period (CSP)
timeFrame: baseline and 2.5 hours
Secondary outcomes:
measure: Change in Number of Voice Breaks
timeFrame: baseline and 2.5 hours
measure: Change in Voice Quality (Overall Severity) With the Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V)
timeFrame: baseline and 2.5 hours
measure: Change in Cepstral Peak Prominence Smoothed (CPPS)
timeFrame: baseline and 2.5 hours
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Noninvasive Neuromodulation Laboratory
state: Minnesota
Study officials:
affiliation: University of Minnesota
name: Mo Chen, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Massachusetts General Hospital
name: Teresa J Kimberley, PhD, PT
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.
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.