Effects of Neuromodulation in Laryngeal Dystonia

NCT05095740 | Recruiting DMC FDA Device

• 2 other identifiers: 2020P003531K24DC018603
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Laryngeal Dystonia; Focal Dystonia

Keywords

transcranial magnetic stimulation; randomized control trial; rTMS

Outcome Measures

Primary Outcomes (2)

• 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).

  Day 1 (baseline), day 5 (post intervention), and Day 12 (follow up) timepoints for both arms of the study.

• Change in Cortical Excitability (intrahemispheric inhibition)

  Intrahemispheric inhibition will be measured with the cortical silent period (cSP) measured in ms

  Day 1 (baseline), Day 5 (post intervention)

Secondary Outcomes (3)

• Subjective Assessment of Phonatory Function

  Day 1 (baseline), Day 5 (post intervention), and Day 12 (follow up) timepoints for both arms of the study.

• Self Ratings of Voice Effort

  Day 1 (baseline), Day 5 (post intervention), and Day 12 (follow up) timepoints for both arms of the study.

• Secondary Objective assessment of phonatory function

  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

  Day 1 (baseline), Day 5 (post intervention), and Day 12 (follow up) timepoints for both arms of the study.

Study Arms (2)

repetitive transcranial magnetic stimulation (rTMS)

ACTIVE COMPARATOR

5 consecutive days of rTMS to the individualized, targeted, left laryngeal motor cortex associated with laryngeal function to down-regulate cortical motor signal to intrinsic laryngeal muscles and improve vocal function of individuals with LD.

Device: repetitive transcranial magnetic stimulation (rTMS)

Sham rTMS

SHAM COMPARATOR

5 consecutive days of sham rTMS to the individualized, targeted, left laryngeal motor cortex associated with laryngeal function to down-regulate cortical motor signal to intrinsic laryngeal muscles and improve vocal function of individuals with LD.

Device: sham rTMS

Interventions

sham rTMS DEVICE

Repetitive 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.

Also known as: sham repetitive transcranial magnetic stimulation

Sham rTMS

repetitive transcranial magnetic stimulation (rTMS) DEVICE

Repetitive transcranial magnetic stimulation used to regulate the contribution of the laryngeal motor cortex to voice production and laryngeal motor muscle activation.

Also known as: transcranial magnetic stimulation

repetitive transcranial magnetic stimulation (rTMS)

Eligibility Criteria

• Age: 21 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Subject has signed the consent form

You may not qualify if:

• Other forms of dystonia
• Vocal fold pathology or paralysis
• Essential tremor
• Laryngeal cancer or other neurologic conditions with medications affecting the central nervous system
• History of laryngeal surgery
• Adults lacking the ability to consent or complete the assessments and intervention
• Seizure in the last 2 years
• Contraindications to rTMS

Sponsors & Collaborators

• National Institute on Deafness and Other Communication Disorders (NIDCD): collaborator
• MGH Institute of Health Professions: lead

Study Sites (1)

Teresa J Kimberley

Boston, Massachusetts, 02129, United States

RECRUITING

Related Publications (16)

• Baylor CR, Yorkston KM, Eadie TL. The consequences of spasmodic dysphonia on communication-related quality of life: a qualitative study of the insider's experiences. J Commun Disord. 2005 Sep-Oct;38(5):395-419. doi: 10.1016/j.jcomdis.2005.03.003.

  PMID: 15963338 BACKGROUND

• Gaskill CS, Awan JA, Watts CR, Awan SN. Acoustic and Perceptual Classification of Within-sample Normal, Intermittently Dysphonic, and Consistently Dysphonic Voice Types. J Voice. 2017 Mar;31(2):218-228. doi: 10.1016/j.jvoice.2016.04.016. Epub 2016 May 27.

  PMID: 27241579 BACKGROUND

• Ludlow CL, Naunton RF, Terada S, Anderson BJ. Successful treatment of selected cases of abductor spasmodic dysphonia using botulinum toxin injection. Otolaryngol Head Neck Surg. 1991 Jun;104(6):849-55. doi: 10.1177/019459989110400614.

  PMID: 1908979 BACKGROUND

• Ali SO, Thomassen M, Schulz GM, Hosey LA, Varga M, Ludlow CL, Braun AR. Alterations in CNS activity induced by botulinum toxin treatment in spasmodic dysphonia: an H215O PET study. J Speech Lang Hear Res. 2006 Oct;49(5):1127-46. doi: 10.1044/1092-4388(2006/081).

  PMID: 17077220 BACKGROUND

• Norris SA, Morris AE, Campbell MC, Karimi M, Adeyemo B, Paniello RC, Snyder AZ, Petersen SE, Mink JW, Perlmutter JS. Regional, not global, functional connectivity contributes to isolated focal dystonia. Neurology. 2020 Oct 20;95(16):e2246-e2258. doi: 10.1212/WNL.0000000000010791. Epub 2020 Sep 10.

  PMID: 32913023 BACKGROUND

• Simonyan K, Ludlow CL. Abnormal activation of the primary somatosensory cortex in spasmodic dysphonia: an fMRI study. Cereb Cortex. 2010 Nov;20(11):2749-59. doi: 10.1093/cercor/bhq023. Epub 2010 Mar 1.

  PMID: 20194686 BACKGROUND

• Chen M, Summers RLS, Prudente CN, Goding GS, Samargia-Grivette S, Ludlow CL, Kimberley TJ. Transcranial magnetic stimulation and functional magnet resonance imaging evaluation of adductor spasmodic dysphonia during phonation. Brain Stimul. 2020 May-Jun;13(3):908-915. doi: 10.1016/j.brs.2020.03.003. Epub 2020 Mar 13.

  PMID: 32289724 BACKGROUND

• Erickson ML. Effects of voicing and syntactic complexity on sign expression in adductor spasmodic dysphonia. Am J Speech Lang Pathol. 2003 Nov;12(4):416-24. doi: 10.1044/1058-0360(2003/087).

  PMID: 14658993 BACKGROUND

• Hirano M, Ohala J. Use of hooked-wire electrodes for electromyography of the intrinsic laryngeal muscles. J Speech Hear Res. 1969 Jun;12(2):362-73. doi: 10.1044/jshr.1202.362. No abstract available.

  PMID: 5808863 BACKGROUND

• Chen M, Deng H, Schmidt RL, Kimberley TJ. Low-Frequency Repetitive Transcranial Magnetic Stimulation Targeted to Premotor Cortex Followed by Primary Motor Cortex Modulates Excitability Differently Than Premotor Cortex or Primary Motor Cortex Stimulation Alone. Neuromodulation. 2015 Dec;18(8):678-85. doi: 10.1111/ner.12337. Epub 2015 Aug 26.

  PMID: 26307511 BACKGROUND

• 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.

  PMID: 28326007 BACKGROUND

• Bradnam LV, Stinear CM, Lewis GN, Byblow WD. Task-dependent modulation of inputs to proximal upper limb following transcranial direct current stimulation of primary motor cortex. J Neurophysiol. 2010 May;103(5):2382-9. doi: 10.1152/jn.01046.2009. Epub 2010 Mar 10.

  PMID: 20220073 BACKGROUND

• 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.

  PMID: 19833552 BACKGROUND

• Siebner HR, Filipovic SR, Rowe JB, Cordivari C, Gerschlager W, Rothwell JC, Frackowiak RS, Bhatia KP. Patients with focal arm dystonia have increased sensitivity to slow-frequency repetitive TMS of the dorsal premotor cortex. Brain. 2003 Dec;126(Pt 12):2710-25. doi: 10.1093/brain/awg282. Epub 2003 Aug 22.

  PMID: 12937071 BACKGROUND

• Murase N, Rothwell JC, Kaji R, Urushihara R, Nakamura K, Murayama N, Igasaki T, Sakata-Igasaki M, Mima T, Ikeda A, Shibasaki H. Subthreshold low-frequency repetitive transcranial magnetic stimulation over the premotor cortex modulates writer's cramp. Brain. 2005 Jan;128(Pt 1):104-15. doi: 10.1093/brain/awh315. Epub 2004 Oct 13.

  PMID: 15483042 BACKGROUND

• Lozeron P, Poujois A, Richard A, Masmoudi S, Meppiel E, Woimant F, Kubis N. Contribution of TMS and rTMS in the Understanding of the Pathophysiology and in the Treatment of Dystonia. Front Neural Circuits. 2016 Nov 10;10:90. doi: 10.3389/fncir.2016.00090. eCollection 2016.

  PMID: 27891079 BACKGROUND

Related Links

• Link to more information on the study or to contact us.

MeSH Terms

Conditions

Dysphonia; Dystonic Disorders

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Voice Disorders; Laryngeal Diseases; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Movement Disorders; Central Nervous System Diseases

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Officials

• Teresa J Kimberley, PhD,PT

  MGH Institute of Health Professions

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Caitlin Koehler, Lab Manager

CONTACT

617-643-6564; brainrecoverylab@mghihp.edu

Teresa J Kimberley, PhD, PT

CONTACT

617-643-9237; tkimberley@mgh.harvard.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants will be randomly assigned to one of two arms of this study (real rTMS or sham). Only the study personnel tasked with setup of the rTMS equipment will know to which group each participant has been randomized so that they can adjust the machine parameters for each participant.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Participants will be randomly assigned to receive 5 consecutive days of either rTMS or sham rTMS. Day 1, baseline (Pre) acoustic, perceptual and patient-reported assessments of voice production and TMS-measured neurophysiology will be performed. Participants will then receive the first rTMS intervention. Day 2, 3 and 4, participants will receive rTMS intervention solely, with no testing. Day 5, the same acoustic, perceptual, patient-reported and assessments will be performed after rTMS intervention. At least 3 months after Post1, participants will cross-over to receive the other intervention. Assessments in Pre2 and Post2, will mirror the timing of Pre1 and Post1 in phase 1. Following treatments, acoustic measures and a global rating of change in vocal function will be evaluated to understand the longevity of our treatment approach. Follow up voice recordings will be obtained using a portable voice recorder given to and returned by participants at their initial visit.

Study Record Dates

• First Submitted: February 15, 2021
• First Posted: October 27, 2021
• Study Start: June 10, 2021
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: February 20, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be made available no later than upon the acceptance of publication of the final dataset.
• Access Criteria: Listed as personnel on Massachusetts General Hospital individualized health plan institutional review board for this study and as determined by the principal investigator.

Locations

US (1)