Feasibility of First Injection of Autologous Adipose Tissue-Derived Stromal Vascular Fraction in Human Scarred Vocal Folds: A Nonrandomized Controlled Trial

Abstract

Importance: Patients with scarred vocal folds, whether congenitally or after phonosurgery, often exhibit dysphonia that negatively affects daily life and is difficult to treat. The autologous adipose tissue-derived stromal vascular fraction (ADSVF) is a readily accessible source of cells with angiogenic, anti-inflammatory, immunomodulatory, and regenerative properties.

Objective: To evaluate the feasibility and tolerability of local injections of autologous ADSVF in patients with scarred vocal folds.

Design, setting, and participants: CELLCORDES (Innovative Treatment for Scarred Vocal Cords by Local Injection of Autologous Stromal Vascular Fraction) is a prospective, open-label, single-arm, single-center, nonrandomized controlled trial with a 12-month follow-up and patient enrollment from April 1, 2016, to June 30, 2017. Eight patients with severe dysphonia attributable to vocal fold scarring associated with a congenital malformation or resulting from microsurgical sequelae (voice handicap index score >60 of 120) completed the study. Data analysis was performed from September 1, 2018, to January 1, 2019.

Interventions: Injection of ADSVF into 1 or 2 vocal folds.

Main outcomes and measures: The primary outcomes were feasibility and the number and severity of adverse events associated with ADSVF-based therapy. The secondary outcomes were changes in vocal assessment, videolaryngostroboscopy, self-evaluation of dysphonia, and quality of life at 1, 6, and 12 months after cell therapy.

Results: Seven women and 1 man (mean [SD] age, 44.6 [10.4] years) were enrolled in this study. Adverse events associated with liposuction and ADSVF injection occurred; most of them resolved spontaneously. One patient received minor treatment to drain local bruising, and another experienced a minor contour defect at the liposuction site. At 12 months, the voice handicap index score was improved in all patients, with a mean (SD) improvement from baseline of 40.1 (21.5) points. Seven patients (88%) were considered to be responders, defined as improvement by 18 points or more in the voice handicap index score (the minimum clinically important difference).

Conclusions and relevance: The findings suggest that autologous ADSVF injection in scarred vocal folds is feasible and tolerable. The findings require confirmation in a randomized clinical trial with a larger population.

Trial registration: ClinicalTrials.gov Identifier: NCT02622464.

Figure 1.. CONSORT Flow Diagram for the Single-Arm, Open-Label, Phase 1 Clinical Trial

Figure 2.. Voice Handicap Index (VHI) Scores During 12-Month Follow-up After Adipose Tissue–Derived Stromal Vascular Fraction (ADSVF) Injection

A, Total mean (SD) VHI score during the 12-month follow-up after ADSVF injection. B, Mean (SD) physical, functional, and emotional VHI subscores. C, Changes in VHI scores from baseline during 12-month follow-up after ADSVF injection for each patient. The dotted blue line represents the minimal shift in the total VHI score required to be clinically significant (18 points). Sample sizes were 8 patients at baseline and months 6 and 12 and 7 patients at month 1 (data missing for patient 4).