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Functional Electrical Stimulation of the Bilaterally Paralyzed Human Larynx

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ClinicalTrials.gov Identifier: NCT04028674
Recruitment Status : Not yet recruiting
First Posted : July 23, 2019
Last Update Posted : May 15, 2020
Sponsor:
Collaborator:
National Institute on Deafness and Other Communication Disorders (NIDCD)
Information provided by (Responsible Party):
David Zealear, Vanderbilt University Medical Center

Brief Summary:
The primary purpose of this project is to evaluate the safety of a laryngeal pacemaker device to provide a new treatment termed bilateral laryngeal pacing for the treatment of bilateral vocal fold paralysis (BVFP) (Aim 1). Outcome measures related to voice and ventilation will also provide initial insights into the efficacy of bilateral (Aim 2) and unilateral (Aim 3) stimulation of the implanted device for the treatment of BVFP.

Condition or disease Intervention/treatment Phase
Bilateral Vocal Fold Paralysis (BVFP) Device: Laryngeal Pacing Device Not Applicable

Detailed Description:

Despite recent advances in medicine, rehabilitation of the paralyzed larynx remains a complex clinical problem. Based on national health statistics, it is anticipated approximately 7,000 patients will be diagnosed with BVFP in the United States each year. BVFP is a serious and often life-threatening clinical condition. The recurrent laryngeal nerve (RLN) carries motor fibers that innervate both the abductor muscle (posterior cricoarytenoid muscle) and adductor muscles of the vocal folds. Damage to the nerve compromises both of these functions and arrests the vocal folds in a near-closed position. With BVFP, voice tends to be functional, but airway compromise is often severe enough to warrant tracheotomy to relieve inspiratory stridor and dyspnea. If spontaneous recovery does not occur within one year, it is likely that the patient's vocal folds will be chronically paralyzed. In such instances, long-term tracheostomy can be considered. Unfortunately, permanent tracheostomy is associated with complications such as tracheal stenosis, chronic infection, and psycho-social impairment. For this reason, laryngeal surgery is usually recommended to enlarge the airway and restore breathing through the mouth. Procedures such as arytenoidectomy, cordotomy, or repeated Botox injections, regarded as the standard of care for enlarging the airway, also have inherent complications. Specifically, they impair voice and compromise airway protection during swallowing. The limitations associated with these current treatments have prompted investigation into a more physiologic, dynamic approach to rehabilitation: reanimation of the paralyzed PCA muscle by functional electrical stimulation (FES). Ideally, stimulation should be applied during the inspiratory phase of respiration to abduct the vocal folds. This has been termed "laryngeal pacing". During non-inspiratory phases, stimulation would cease, and the vocal folds would passively relax to the midline to allow for normal voice production and airway protection. Previously, our clinical trial of unilateral pacing demonstrated a significantly greater return of ventilation without any compromise of voice or swallowing. However, the level of ventilation was only marginally better than that associated with cordotomy.

In the current project, we will investigate the safety of a novel intervention (laryngeal pacing) for BVFP (Aim 1). The overarching hypothesis is that neuromuscular activation of the PCA muscles bilaterally reestablishes bilateral glottal opening and ventilation through the mouth without alteration of voice or swallowing, compared to a sham-operated control (Aim 2). The ventilation from bilateral pacing should be significantly greater than from unilateral pacing and allow the patient to engage in a normal pre-paralysis activity level (Aim 3).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Following implantation of the laryngeal pacing device and the 2-week wound check, participants will be randomized to their treatment group (Early Activation vs. Delayed Activation) and unilateral stimulation side (Right PCA vs. Left PCA) using the REDCap randomization module.

  1. To treatment group at a 3:1 ratio—Either the Early Activation Group (n=9) or the Delayed Activation Group (n=3)
  2. To unilateral stimulation side at a 1:1 ratio—The side for unilateral stimulation will be either the left PCA muscle (n=6), or the right PCA muscle (n=6)
Masking: Single (Outcomes Assessor)
Masking Description:

The procedures which will be blinded include PIF, CAPE-V, NGA, X-Tol, MBS and CXR.

  • PIF: One member of the research staff will be unblinded and control the pacer programmer. The testing condition will be programmed prior to start of test. Both patient and staff administering the test will be blinded to testing condition.
  • CAPE-V: Clinically-certified SLPs involved in perceptual ratings of voice quality will be blinded to experimental testing condition and data collection timepoint.
  • NGA: NGA is analyzed from stills of the glottis collected during endoscopy. These images will be randomized and de-identified before analysis to blind the rater.
  • X-Tol: One member of the research staff will be unblinded and control the pacer programmer. The testing condition will be programmed prior to start of test. Both patient and staff administering the test will be blinded to testing condition.
  • MBS and CXR: Technicians reading these exams will be blinded to treatment condition.
Primary Purpose: Device Feasibility
Official Title: Functional Electrical Stimulation of the Bilaterally Paralyzed Human Larynx
Estimated Study Start Date : July 2020
Estimated Primary Completion Date : December 2025
Estimated Study Completion Date : December 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Paralysis

Arm Intervention/treatment
Experimental: Early Activation of Laryngeal Pacing device
Early Activation of the laryngeal pacing device (n=9) at one month post-implantation.
Device: Laryngeal Pacing Device
Device is an implantable neurostimulation system designed to deliver low-intensity electrical impulses to nerve structures.

Sham Comparator: Delayed Activation of Laryngeal Pacing device
Delayed activation of the laryngeal pacing device (n=3) at two months post-implantation.
Device: Laryngeal Pacing Device
Device is an implantable neurostimulation system designed to deliver low-intensity electrical impulses to nerve structures.




Primary Outcome Measures :
  1. Improved ventilation due to laryngeal pacing device as assessed by increase in standard assessment testing (peak inspiratory flow or PIF). [ Time Frame: 12 months ]
  2. Better voice quality as assessed by decrease in standard assessment testing (Consensus Auditory Perceptual Evaluation of Voice or CAPE-V). [ Time Frame: 12 months ]

Secondary Outcome Measures :
  1. Increased glottal area due to laryngeal pacing device as assessed by increase in normalized glottal area (NGA) results. [ Time Frame: 12 months ]
  2. Increase in exercise tolerance due to laryngeal pacing device as assessed by treadmill testing. [ Time Frame: 12 months ]
  3. Better quality of life (QOL) outcomes due to laryngeal pacing device, self assessed via patient reported outcome surveys. [ Time Frame: 12 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   22 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Provision of signed and dated informed consent form.
  • Willingness to comply with all study procedures and availability for the duration of the study.
  • Male or female adult patients, 22 years of age or older.
  • Diagnosis of bilateral vocal fold paralysis, at least ten months prior to study enrollment. This diagnosis will be documented via medical records and confirmed during the onsite screening visit by a Vanderbilt board certified laryngologist via endoscopy, electromyography and direct laryngoscopy.
  • Demonstrated glottal opening bilaterally (abductory response) upon percutaneous needle stimulation of PCA muscles (i.e. mean NGA ≥0.05 per vocal fold tested).
  • Patients with or without a tracheostomy.

Exclusion Criteria:

  • Any active illness that is associated with an auto-immune disorder (such as diabetes).
  • History of cardiac dysrhythmias or implanted cardiac pacemaker.
  • Cardiac irregularities identified in screening electrocardiogram.
  • Any electronic implanted medical device that, in the investigator's opinion, could interact with the laryngeal pacemaker.
  • Active cardiac disease manifested by unstable angina, recent myocardial infarction, malignant arrhythmias, uncontrolled hypertension (diastolic greater than 110), or decompensated congestive heart failure.
  • Patients with underlying comorbidities that, in the investigator's opinion, could potentially warrant a need for oxygen therapy, including but not limited to: Chronic obstructive pulmonary disease, asthma, emphysema, recurrent bronchitis, pneumonia or interstitial lung disease.
  • Bilateral laryngeal immobility from stenosis or arthritis.
  • Currently being treated for bilateral vocal fold paralysis via botulinum toxin (Botox). Patients who have received Botox ≥6 months prior to enrollment may be eligible for enrollment.
  • Poor surgical risk patients as determined by the treating surgeon or Vanderbilt Preoperative Evaluation Center (VPEC).
  • The abundance of interstitial fat may impede the surgical dissection. In the opinion of the principal investigator or treating physician(s), patients with factors that may complicate the surgical intervention will be excluded.
  • Known allergy to barium dye or anesthetics.
  • Known allergy to any of the device materials.
  • Patients with pre-existing liquid dysphagia.
  • Presence of significant tracheal narrowing.
  • Any anatomical abnormality that would jeopardize safe implantation, per the surgeon.
  • Any medical condition, that in the opinion of the principal investigator or treating physician would jeopardize the outcome or welfare of the participant.
  • Any previous medical treatment that in the opinion of the principal investigator or treating physician would confound the effects of laryngeal pacing.
  • Females who are pregnant or plan a pregnancy within 2 years. A pregnancy test will be done as part of the routine pre-operative assessment for all females of child-bearing potential.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04028674


Contacts
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Contact: Kate Von Wahlde, MJ, CCRP 615-322-0333 kate.vonwahlde@vumc.org

Locations
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United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Vanderbilt University Medical Center
National Institute on Deafness and Other Communication Disorders (NIDCD)
Investigators
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Principal Investigator: David L. Zealear, PhD Vanderbilt University Medical Center
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Responsible Party: David Zealear, Professor, Department of Otolaryngology, Vanderbilt University Medical Center
ClinicalTrials.gov Identifier: NCT04028674    
Other Study ID Numbers: 200932
5U01DC016033 ( U.S. NIH Grant/Contract )
First Posted: July 23, 2019    Key Record Dates
Last Update Posted: May 15, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Additional relevant MeSH terms:
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Paralysis
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms