Silk Protein Microparticle-based Filler for Injection Augmentation

Study Overview
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Brief Summary
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This study will investigate the safety and efficacy of a silk protein microparticle-based filler for vocal fold injection augmentation to treat dysphonia/dysphagia secondary to vocal fold paralysis. Participants will receive one injection and follow-up for a planned period of 12 months.

Detailed Description
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Vocal fold paralysis is a clinical condition that arises commonly as a complication of surgery, endotracheal intubation, malignancy, or idiopathic etiologies. It often results in glottal insufficiency, which is the inability of the true vocal folds to meet and achieve complete closure during normal physiologic functions such as speech, swallowing, and coughing. The presence of vocal fold paralysis with glottal insufficiency can lead to decreased quality-of-life, as well as increase risks of complications such as aspiration pneumonia. Current treatments for vocal fold paralysis are based around techniques to medialize the paralyzed vocal fold. One manner in which this is done is via injection of a filler or bulking agent into the vocal fold in order to augment it. Injection augmentation has many advantages including its minimally invasive nature, overall safety and low risk/complication rate, immediate clinical effect, and ability to perform it at the bedside or in-office. Various materials are used for injection augmentation including autologous fat, hyaluronic acid, collagen, carboxymethylcellulose, and calcium hydroxyapatite. However, all of the current injection choices have individual limitations such as temporary effect, unpredictability due to variable resorption by the body, unfavorable mechanical properties, and challenging handling attributes. Silk is derived from the Bombyx mori silk worm and has a long history as a surgical biomaterial. Surgical scaffolds derived from silk have been used for reconstructive surgery, due to its ability to allow cellular infiltration and encourage tissue regeneration/remodeling. Given the potential advantages of such a material, Brown et al engineered and studied a novel silk protein microparticle-based filler material suitable for injection augmentation. Patients with unilateral vocal fold paralysis identified at the study sites will be offered participation in this study to receive injection augmentation of the paralyzed vocal fold with the filler material under investigation. Outcome measures evaluated pre- and post-injection and over follow-up visits will include various patient reported quality of life indices, objective clinical assessments of voice, laryngeal videostroboscopy examinations, and acoustic/aerodynamic testing. The investigators hypothesize that the novel silk protein microparticle-based filler will have a favorable safety profile for use as an injectable material in the human larynx and it will produce durable clinical benefit lasting up to 12 months.

Official Title
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Safety and Efficacy of a Silk Protein Microparticle-based Filler for Injection Augmentation in Treating Unilateral Vocal Fold Paralysis

Conditions
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Vocal Cord Paralysis Unilateral, Dysphonia, Dysphagia, Oropharyngeal

Intervention / Treatment
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* Procedure: Silk Microparticle Filler Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Unilateral vocal fold immobility with glottal insufficiency present for at least 2 weeks from onset Willingness to partake in study and follow-up as documented by signed informed consent Exclusion Criteria: History of allergy/hypersensitivity to silk or silk containing products History of allergy/hypersensitivity to hyaluronic acid (HA) or HA containing products History of allergy/hypersensitivity to lidocaine or amide-based anesthetics History of an autoimmune condition Significant immunocompromised state (i.e. immunosuppression s/p transplantation) Pregnancy Active infection or inflammation in the larynx Comorbid known laryngeal conditions including but not limited to vocal fold scar, vocal tremor, laryngeal dystonia, etc. that would warrant other interventions for optimal treatment History of laryngeal surgery Life expectancy of less than 6 months

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Single vocal fold injection of study material with possible booster injection, and follow-up of 12 months post injection.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Silk Microparticle Filler Injection<br>A silk protein microparticle-based filler will be injected deep to the thyroarytenoid muscle of the paralyzed vocal fold to augment/medialize its position. | Procedure: Silk Microparticle Filler Injection<br>* A silk protein microparticle-based filler will be injected deep to the thyroarytenoid muscle of the paralyzed vocal fold to augment/medialize its position.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events as assessed by FDA/CBER Adverse Event Severity Grading Scale | Adverse event severity grading scale from 1 to 4, with grade 1 as mild, grade 2 as moderate, grade 3 as severe, and grade 4 potentially life-threatening. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Life as assessed by Voice Handicap Index-10 (VHI-10) | VHI-10 is a patient questionnaire with 10 statements rated from 0 to 4 with overall scale 0-40. | 12 months | 
| Quality of Life as assessed by Vocal Fatigue Index (VFI) | VFI is a patient questionnaire with 19 statements rated from 0-4 with overall scale 0-76. | 12 months | 
| Quality of Life as assessed by Dyspnea Index (DI) | DI is a patient questionnaire with 10 statements rated from 0 to 4 with overall scale 0-40. | 12 months | 
| Quality of Life as assessed by Eating Assessment Tool (EAT-10) | EAT-10 is a patient questionnaire with 10 statements rated from 0 to 4 with overall scale 0-40. | 12 months | 
| Objective Vocal Quality as assessed by experts using the Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) instrument | Blinded evaluations of audio voice recordings will be performed by laryngologists and speech-language pathologists using the CAPE-V, which grades overall severity, roughness, breathiness, strain, pitch, and loudness from 0-100. | 12 months | 
| Vocal Fold Appearance as assessed by experts using a modified version of the Voice-Vibratory Assessment with Laryngeal Imaging (VALI) form | Blinded assessments of recorded laryngeal videostroboscopy exams will be performed by laryngologists and speech-language pathologists using a modified version of the VALI, which is a graphical rating form to grade various components seen on stroboscopy. | 12 months | 
| Objective Acoustic Testing as assessed by fundamental frequency | Measurement of fundamental frequency (F0) during sustained vowel phonation. | 12 months | 
| Objective Acoustic Testing as assessed by Sound Pressure Level (SPL) | Measurement of minimum/maximum SPL during phonation. | 12 months | 
| Objective Acoustic Testing as assessed by Cepstral Peak Prominence (CPP) | Measurement of CPP during phonation. | 12 months | 
| Objective Aerodynamic Testing as assessed by Vital Capacity (VC) | Measurement of VC. | 12 months | 
| Objective Aerodynamic Testing as assessed by Maximum Phonation Time (MPT) | Measurement of MPT. | 12 months | 
| Objective Aerodynamic Testing as assessed by Mean Glottal Flow Rate (MGFR) | Measurement of MGFR. | 12 months | 
| Objective Aerodynamic Testing as assessed by Subglottal Pressure (SGP) | Measurement of SGP. | 12 months | 
| Objective Aerodynamic Testing as assessed by Cough Velocity (CV) | Measurement of maximum CV. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vocal fold paralysis, glottal insufficiency, vocal fold injection, augmentation, medialization, laryngoplasty, silk