Yue Ma1, Jennifer Long1, Milan R Amin2, Ryan C Branski2, Edward J Damrose3, Chih-Kwang Sung3, Stratos Achlatis2, Ann Kearney3, Dinesh K Chhetri1. 1. Department of Head and Neck Surgery, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California. 2. Department of Otolaryngology-Head and Neck Surgery, New York University Voice Center, New York University School of Medicine, New York, New York. 3. Department of Otolaryngology-Head and Neck Surgery, Stanford School of Medicine, Stanford University, Stanford, California, U.S.A.
Abstract
OBJECTIVES/HYPOTHESIS: To assess the safety and efficacy of autologous cultured fibroblasts (ACFs) to treat dysphonia related to vocal fold scar and age-related vocal atrophy (ARVA). STUDY DESIGN: Randomized, double-blinded, placebo-controlled, multi-institutional, phase II trial. METHODS: ACFs were expanded from punch biopsies of the postauricular skin in each subject; randomization was 2:1 (treatment vs. placebo). Three injections of 1-2 × 107 cells or placebo saline was performed at 4-week intervals for each vocal fold. Follow-up was performed at 4, 8, and 12 months. The primary outcome was improved mucosal waves. Secondary outcomes included Voice Handicap Index (VHI)-30, patient reported voice quality outcomes, and perceptual analysis of voice. RESULTS: Fifteen subjects received ACF and six received saline injections. At 4, 8, and 12 months after ACF treatments, a significant improvement in mucosal wave grade relative to baseline was observed in both vocal scar and ARVA groups. Relative to control group, mucosal waves were significantly improved in the ARVA group at 4 and 8 months. Perceptual analysis significantly improved in the vocal scar group 12 months after ACF treatments compared to controls. Vocal scar group reported significantly improved vocal quality from baseline. VHI and expert rater voice grade improved in both groups, but did not achieve significance. No adverse events related to fibroblast injections were observed. CONCLUSIONS: In this cohort, injection of ACFs into the vocal fold lamina propria (LP) was safe and significantly improved mucosal waves in patients with vocal scar and ARVA. ACF may hold promise to reconstruct the LP. LEVEL OF EVIDENCE: 1 Laryngoscope, 130:2650-2658, 2020.
RCT Entities:
OBJECTIVES/HYPOTHESIS: To assess the safety and efficacy of autologous cultured fibroblasts (ACFs) to treat dysphonia related to vocal fold scar and age-related vocal atrophy (ARVA). STUDY DESIGN: Randomized, double-blinded, placebo-controlled, multi-institutional, phase II trial. METHODS: ACFs were expanded from punch biopsies of the postauricular skin in each subject; randomization was 2:1 (treatment vs. placebo). Three injections of 1-2 × 107 cells or placebo saline was performed at 4-week intervals for each vocal fold. Follow-up was performed at 4, 8, and 12 months. The primary outcome was improved mucosal waves. Secondary outcomes included Voice Handicap Index (VHI)-30, patient reported voice quality outcomes, and perceptual analysis of voice. RESULTS: Fifteen subjects received ACF and six received saline injections. At 4, 8, and 12 months after ACF treatments, a significant improvement in mucosal wave grade relative to baseline was observed in both vocal scar and ARVA groups. Relative to control group, mucosal waves were significantly improved in the ARVA group at 4 and 8 months. Perceptual analysis significantly improved in the vocal scar group 12 months after ACF treatments compared to controls. Vocal scar group reported significantly improved vocal quality from baseline. VHI and expert rater voice grade improved in both groups, but did not achieve significance. No adverse events related to fibroblast injections were observed. CONCLUSIONS: In this cohort, injection of ACFs into the vocal fold lamina propria (LP) was safe and significantly improved mucosal waves in patients with vocal scar and ARVA. ACF may hold promise to reconstruct the LP. LEVEL OF EVIDENCE: 1 Laryngoscope, 130:2650-2658, 2020.
Authors: A Mattei; J Magalon; B Bertrand; C Philandrianos; J Veran; A Giovanni Journal: Eur Ann Otorhinolaryngol Head Neck Dis Date: 2017-07-06 Impact factor: 2.080
Authors: William E Karle; Samuel N Helman; Amy Cooper; Yuan Zhang; Michael J Pitman Journal: Ann Otol Rhinol Laryngol Date: 2018-01-17 Impact factor: 1.547
Authors: Eric K Tran; Yazeed Alhiyari; Kevin Juarez; Bhavani Shankara Gowda; Feng Schrader; Dipti P Sajed; Jennifer L Long Journal: Laryngoscope Investig Otolaryngol Date: 2022-09-26