Efficacy of Autologous Adipose-Derived Stromal Vascular Fraction Injection Versus Placebo in Patients with Scarred Vocal Folds

The primary objective of this study is to evaluate and compare the **efficacy** of fresh autologous adipose-derived stromal vascular fraction (ADSVF) injection against a placebo, which consists of saline solution and human serum albumin, in treating dysphonia associated with **scarred vocal folds**. This assessment is based on a self-evaluation using the Voice Handicap Index, with a significant improvement defined as an increase of 18 points or more, measured at 6 months post-treatment. This objective is clinically relevant as it aims to address the functional impairment caused by scarred vocal folds, potentially offering a novel therapeutic approach.

Secondary objectives include:

• Evaluating the safety and feasibility of stromal vascular fraction injection, whether fresh or thawed, based on per-operative and post-operative criteria.
• Assessing and comparing the efficacy of fresh ADSVF injection at 1 month and 6 months post-treatment in comparison to placebo.

The clinical trial involves participants diagnosed with **scarred vocal folds**, either congenital or resulting from phonosurgery. The study population includes both male and female subjects aged between 18 and 70 years, all of whom are in good general health. The trial does not involve a vulnerable population. Participants were selected based on specific criteria, including a Voice Handicap Index score greater than 50 out of 120 and a scarred middle third observed in videolaryngostroboscopy. Additionally, there is a requirement for a minimum six-month interval post-initial surgery if applicable. Women of child-bearing age must have a negative pregnancy test and use contraception. The sponsor has not provided information regarding the total number of participants. Lifestyle factors such as diet and physical activity are not specified in the trial details.

The clinical trial is designed as a **randomized, double-blind, controlled** study to evaluate the efficacy of autologous adipose tissue-derived stromal vascular fraction cells in treating **scarred vocal folds**. The trial will compare the active treatment against a placebo, which consists of a saline solution and human serum albumin. The study is set to run from September 22, 2022, to September 22, 2027, with recruitment having commenced on the start date. Participants will be involved in the trial for a maximum treatment period of one month, with the primary endpoint being a significant improvement in the Voice Handicap Index (VHI) score by 18 points or more at six months post-treatment.

Study visits are structured to include an initial screening visit, where eligibility is confirmed based on criteria such as age (18-70 years), a VHI score greater than 50/120, and a diagnosis of scarred vocal folds. Following the screening, participants will undergo the treatment phase, which involves local injection of either the active treatment or placebo. Follow-up visits will occur at one month and six months post-treatment to assess changes in VHI scores and other secondary endpoints, including self-evaluation of dysphonia, voice acoustic and aerodynamic measurements, and videolaryngostroboscopy. The end-of-study visit will mark the conclusion of participant involvement, where final assessments will be conducted.

Participants may be withdrawn from the study early if they experience adverse events related to the treatment, fail to comply with study procedures, or withdraw consent. The trial's design ensures that neither the participants nor the investigators are aware of the treatment allocations, maintaining the integrity of the double-blind methodology. The study aims to provide robust data on the efficacy of the treatment, contributing to the understanding and management of scarred vocal folds.

The clinical trial involves the administration of three distinct treatments, each delivered as a **suspension for injection** via local injection. The first treatment is the experimental medication "SVF 5 inj prep," which contains **autologous adipose tissue-derived stromal vascular fraction cells**. This advanced therapy medicinal product is administered at a maximum daily dose of 10 million organisms, with the same total dose amount, over a treatment period of one day. The cells are derived from the participant's own adipose tissue, ensuring a personalized approach to therapy. The administration is monitored to ensure compliance with the dosing schedule.

The second treatment, "thawed SVF 5 inj prep," also contains **autologous adipose tissue-derived stromal vascular fraction cells**. Similar to the first treatment, it is classified as an advanced therapy medicinal product and is administered at a maximum daily and total dose of 10 million organisms. The treatment period is limited to one day, and the route of administration is local injection. Participant compliance is closely monitored to ensure adherence to the protocol.

The third treatment is a placebo, "Placebo SVF inj prep," which consists of a **suspension for injection** containing **sodium chloride** and **human serum albumin 5%**. This placebo serves as the comparator treatment in the study, providing a baseline for evaluating the efficacy of the experimental therapies. The placebo is administered at a maximum daily and total dose of 2 ml, with a treatment period of one day. The administration is conducted via local injection, and participant compliance is monitored to maintain the integrity of the trial.

Efficacy in this clinical trial will be assessed by evaluating the impact of fresh autologous adipose-derived stromal vascular fraction injection compared to a placebo on **dysphonia** associated with scarred vocal cords. The primary endpoint for efficacy evaluation is the change from baseline in self-evaluation using the Voice Handicap Index (VHI). A clinically significant improvement is defined as a shift of 18 points or greater in the total VHI score, as per Jacobson's criteria. This assessment will be conducted at 6 months post-treatment.

Secondary endpoints include the VHI at 1 month, self-evaluation of dysphonia on a 0-10 scale, voice acoustic measurements, voice aerodynamic measurements such as maximum phonation time, perceptive analysis using the GRB scale, and videolaryngostroboscopy. Additionally, the incidence of related adverse events will be monitored. These parameters will be measured using validated scales and instruments at specified timepoints throughout the trial duration.