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.

Conflict of interest statement

Conflict of Interest Disclosures: Drs Matteis and Giovanni reported receiving grants from Fondation de l'Avenir pour la Recherche Médicale Appliquée and Fondation des Gueules Cassées during the conduct of the study. No other disclosures were reported.

Figures

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).