Autologous Circulating Extracellular Vesicles for Total-Type Sudden Sensorineural Hearing Loss

Total-type sudden sensorineural hearing loss (defined in this study as severe-to-profound sudden sensorineural hearing loss with pure-tone average (PTA) \>70 dB HL) represents one of the poorer-prognosis subtypes of sudden sensorineural hearing loss (SSNHL). It is characterized by severe or profound sensorineural hearing decline occurring within 72 hours, frequently accompanied by tinnitus, aural fullness, vertigo and other symptoms. Although glucocorticoid-based comprehensive therapy has been widely applied in clinical practice, overall prognosis remains unsatisfactory for patients with total-type SSNHL, with low hearing recovery rates. Long-term hearing loss impairs verbal communication, sound source localization and quality of life, and is also associated with anxiety, depression and cognitive decline. Some patients further require hearing rehabilitation with hearing aids or auditory implantation, imposing substantial psychological and economic burdens on individuals and families. Therefore, exploring safer and more innovative therapeutic strategies carries important clinical significance. Extracellular vesicles (EVs) therapy is an emerging cell-free therapeutic technology. Previous pre-clinical studies have demonstrated that EVs can ameliorate inner-ear injury via anti-inflammatory, anti-oxidative-stress and neuroprotective effects, showing promising therapeutic potential in animal models of noise-induced and ototoxic drug-induced hearing loss. The investigators' prior research revealed that EV treatment effectively preserved hearing and alleviated cochlear damage in noise-deafened mice. Meanwhile, the investigators have completed a prospective, randomized exploratory clinical trial (NCT06707389). Its results indicated that intratympanic injection of extracellular vesicles (EVs) yielded favorable safety profiles in total-type SSNHL, without serious adverse events observed, and demonstrated a trend toward superior clinical benefits over conventional therapy in terms of hearing recovery and speech recognition improvement. Based on the above evidence, the investigators intend to conduct a multicenter, prospective, superiority-design randomized controlled clinical trial enrolling 146 patients with total-type SSNHL. This study will systematically evaluate the efficacy and safety of intratympanic autologous circulating extracellular vesicles (C-EVs) combined with glucocorticoid therapy, so as to provide new evidence-based medical data and therapeutic options for total-type SSNHL.