Clinical trial NCT03790956: Silk Protein Microparticle-based Filler for Injection Augmentation
Official title: Safety and Efficacy of a Silk Protein Microparticle-based Filler for Injection Augmentation in Treating Unilateral Vocal Fold Paralysis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Vocal Cord Paralysis Unilateral
Dysphonia
Dysphagia, Oropharyngeal
Keywords: vocal fold paralysis
glottal insufficiency
vocal fold injection
augmentation
medialization
laryngoplasty
silk
Lead sponsor: University of Southern California
Sponsor class: OTHER
Collaborators: name: Sofregen Medical, Inc.
First posted: 2019-01-02
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single vocal fold injection of study material with possible booster injection, and follow-up of 12 months post injection.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events as assessed by FDA/CBER Adverse Event Severity Grading Scale
timeFrame: 12 months
Secondary outcomes:
measure: Quality of Life as assessed by Voice Handicap Index-10 (VHI-10)
timeFrame: 12 months
measure: Quality of Life as assessed by Vocal Fatigue Index (VFI)
timeFrame: 12 months
measure: Quality of Life as assessed by Dyspnea Index (DI)
timeFrame: 12 months
measure: Quality of Life as assessed by Eating Assessment Tool (EAT-10)
timeFrame: 12 months
measure: Objective Vocal Quality as assessed by experts using the Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) instrument
timeFrame: 12 months
measure: Vocal Fold Appearance as assessed by experts using a modified version of the Voice-Vibratory Assessment with Laryngeal Imaging (VALI) form
timeFrame: 12 months
measure: Objective Acoustic Testing as assessed by fundamental frequency
timeFrame: 12 months
measure: Objective Acoustic Testing as assessed by Sound Pressure Level (SPL)
timeFrame: 12 months
measure: Objective Acoustic Testing as assessed by Cepstral Peak Prominence (CPP)
timeFrame: 12 months
measure: Objective Aerodynamic Testing as assessed by Vital Capacity (VC)
timeFrame: 12 months
measure: Objective Aerodynamic Testing as assessed by Maximum Phonation Time (MPT)
timeFrame: 12 months
measure: Objective Aerodynamic Testing as assessed by Mean Glottal Flow Rate (MGFR)
timeFrame: 12 months
measure: Objective Aerodynamic Testing as assessed by Subglottal Pressure (SGP)
timeFrame: 12 months
measure: Objective Aerodynamic Testing as assessed by Cough Velocity (CV)
timeFrame: 12 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southern California
state: California
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.