MedPath

Silk Protein Microparticle-based Filler for Injection Augmentation

Not Applicable
Completed
Conditions
Vocal Cord Paralysis Unilateral
Dysphagia, Oropharyngeal
Dysphonia
Interventions
Procedure: Silk Microparticle Filler Injection
Registration Number
NCT03790956
Lead Sponsor
University of Southern California
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
11
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Silk Microparticle Filler InjectionSilk Microparticle Filler InjectionA silk protein microparticle-based filler will be injected deep to the thyroarytenoid muscle of the paralyzed vocal fold to augment/medialize its position.
Primary Outcome Measures
NameTimeMethod
Incidence of Treatment-Emergent Adverse Events as assessed by FDA/CBER Adverse Event Severity Grading Scale12 months

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.

Secondary Outcome Measures
NameTimeMethod
Objective Acoustic Testing as assessed by Cepstral Peak Prominence (CPP)12 months

Measurement of CPP during phonation.

Objective Acoustic Testing as assessed by fundamental frequency12 months

Measurement of fundamental frequency (F0) during sustained vowel phonation.

Quality of Life as assessed by Voice Handicap Index-10 (VHI-10)12 months

VHI-10 is a patient questionnaire with 10 statements rated from 0 to 4 with overall scale 0-40.

Quality of Life as assessed by Vocal Fatigue Index (VFI)12 months

VFI is a patient questionnaire with 19 statements rated from 0-4 with overall scale 0-76.

Vocal Fold Appearance as assessed by experts using a modified version of the Voice-Vibratory Assessment with Laryngeal Imaging (VALI) form12 months

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.

Objective Aerodynamic Testing as assessed by Vital Capacity (VC)12 months

Measurement of VC.

Objective Aerodynamic Testing as assessed by Maximum Phonation Time (MPT)12 months

Measurement of MPT.

Quality of Life as assessed by Eating Assessment Tool (EAT-10)12 months

EAT-10 is a patient questionnaire with 10 statements rated from 0 to 4 with overall scale 0-40.

Objective Acoustic Testing as assessed by Sound Pressure Level (SPL)12 months

Measurement of minimum/maximum SPL during phonation.

Objective Aerodynamic Testing as assessed by Subglottal Pressure (SGP)12 months

Measurement of SGP.

Quality of Life as assessed by Dyspnea Index (DI)12 months

DI is a patient questionnaire with 10 statements rated from 0 to 4 with overall scale 0-40.

Objective Vocal Quality as assessed by experts using the Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) instrument12 months

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.

Objective Aerodynamic Testing as assessed by Mean Glottal Flow Rate (MGFR)12 months

Measurement of MGFR.

Objective Aerodynamic Testing as assessed by Cough Velocity (CV)12 months

Measurement of maximum CV.

Trial Locations

Locations (1)

University of Southern California

🇺🇸

Los Angeles, California, United States

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