Silk Protein Microparticle-based Filler for Injection Augmentation

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

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.

Study Overview

• Status: Completed
• Conditions: Dysphonia; Vocal Cord Paralysis Unilateral; Dysphagia, Oropharyngeal
• Intervention / Treatment: Procedure: Silk Microparticle Filler Injection

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Michael Johns, MD; Phone Number: 323-442-5577; Email: michael.johns@med.usc.edu
• Study Contact Backup: Name: Neel Bhatt, MD; Phone Number: 323-442-5579; Email: neel.bhatt@med.usc.edu

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Southern California
• Collaborators: Sofregen Medical, Inc.

Publications and helpful links

General Publications

• Spector BC, Netterville JL, Billante C, Clary J, Reinisch L, Smith TL. Quality-of-life assessment in patients with unilateral vocal cord paralysis. Otolaryngol Head Neck Surg. 2001 Sep;125(3):176-82. doi: 10.1067/mhn.2001.117714.
• Brown JE, Gulka CP, Giordano JEM, Montero MP, Hoang A, Carroll TL. Injectable Silk Protein Microparticle-based Fillers: A Novel Material for Potential Use in Glottic Insufficiency. J Voice. 2019 Sep;33(5):773-780. doi: 10.1016/j.jvoice.2018.01.017. Epub 2018 Mar 30.
• Etienne O, Schneider A, Kluge JA, Bellemin-Laponnaz C, Polidori C, Leisk GG, Kaplan DL, Garlick JA, Egles C. Soft tissue augmentation using silk gels: an in vitro and in vivo study. J Periodontol. 2009 Nov;80(11):1852-8. doi: 10.1902/jop.2009.090231.
• Bellas E, Panilaitis BJ, Glettig DL, Kirker-Head CA, Yoo JJ, Marra KG, Rubin JP, Kaplan DL. Sustained volume retention in vivo with adipocyte and lipoaspirate seeded silk scaffolds. Biomaterials. 2013 Apr;34(12):2960-8. doi: 10.1016/j.biomaterials.2013.01.058. Epub 2013 Jan 29.
• Kijanska M, Marmaras A, Hegglin A, Kurtcuoglu V, Giovanoli P, Lindenblatt N. In vivo characterization of the integration and vascularization of a silk-derived surgical scaffold. J Plast Reconstr Aesthet Surg. 2016 Aug;69(8):1141-50. doi: 10.1016/j.bjps.2016.01.017. Epub 2016 Feb 5.
• Rosen CA, Gartner-Schmidt J, Casiano R, Anderson TD, Johnson F, Remacle M, Sataloff RT, Abitbol J, Shaw G, Archer S, Zraick RI. Vocal fold augmentation with calcium hydroxylapatite: twelve-month report. Laryngoscope. 2009 May;119(5):1033-41. doi: 10.1002/lary.20126.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2020
• Primary Completion (Actual): March 15, 2023
• Study Completion (Actual): March 15, 2023

Study Registration Dates

• First Submitted: November 25, 2018
• First Submitted That Met QC Criteria: December 29, 2018
• First Posted (Actual): January 2, 2019

Study Record Updates

• Last Update Posted (Actual): May 10, 2023
• Last Update Submitted That Met QC Criteria: May 8, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: augmentation; silk; vocal fold paralysis; glottal insufficiency; vocal fold injection; medialization; laryngoplasty
• Additional Relevant MeSH Terms: Digestive System Diseases; Nervous System Diseases; Respiratory Tract Diseases; Neurologic Manifestations; Gastrointestinal Diseases; Pharyngeal Diseases; Otorhinolaryngologic Diseases; Esophageal Diseases; Cranial Nerve Diseases; Laryngeal Diseases; Vagus Nerve Diseases; Voice Disorders; Deglutition Disorders; Paralysis; Vocal Cord Paralysis; Dysphonia
• Other Study ID Numbers: APP-18-05229

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No