A Randomized Trial of Intratympanic Drug Delivery: Evaluating the Efficacy and Safety of Dexamethasone-Loaded Exosomes Versus Standard Therapy in Acute Sensorineural Hearing Loss.

Официальное название

A Phase II, Randomized Trial of Intratympanic Drug Delivery: Evaluating the Efficacy and Safety of Dexamethasone-Loaded Exosomes Versus Standard Therapy in Acute Sensorineural Hearing Loss.

Обзор

Primary Objective To compare the efficacy of a single course of IT Exo-Dex versus conventional IT dexamethasone and exosome vehicle alone, as measured by the mean change in pure-tone average (PTA; 0.5, 1, 2, 4 kHz) from baseline to the 4-week post-treatment endpoint. Secondary Objectives 1. To determine the safety and tolerability profile of IT Exo-Dex. 2. To compare the rate of hearing recovery (defined as \>10 dB improvement in PTA or recovery to within 10 dB of contralateral ear) among the three treatment groups at 1, 4, and 12 weeks. 3. To assess changes in auditory function via Auditory Brainstem Response (ABR) thresholds and Otoacoustic Emissions (OAEs). 4. To characterize the pharmacokinetics and inner ear biodistribution of Exo-Dex using advanced imaging modalities (e.g., MRI with exosome-contrast agents in a sub-study cohort if applicable).

Подробное описание

SSNHL is defined as a rapid-onset hearing loss of ≥30 dB over at least three contiguous frequencies within a 72-hour period, with an incidence of 5-20 per 100,000 persons annually (1).

The idiopathic nature of most cases suggests multifactorial pathogenesis, including viral infections, autoimmune responses, and vascular ischemia, culminating in cochlear inflammation and oxidative stress (2).

The standard of care involves systemic corticosteroids, with salvage IT corticosteroid injections for non-responders. However, the blood-labyrinth barrier and the round window membrane pose significant anatomical and physiological barriers to effective drug delivery, resulting in sub-therapeutic inner ear drug levels and potential systemic toxicity (3, 4).

Exosomes (30-150 nm) are natural vesicles secreted by most cell types, playing crucial roles in intercellular communication via transport of proteins, lipids, and nucleic acids (5). As drug delivery vehicles, they offer intrinsic biocompatibility, low immunogenicity, and an innate ability to cross biological barriers.

Preclinical studies demonstrate that exosomes can be loaded with therapeutic agents, such as dexamethasone, and targeted to specific tissues, enhancing drug bioavailability and retention while minimizing off-target effects (6, 7).

The investigators hypothesize that IT administration of exosomes loaded with dexamethasone will result in superior therapeutic outcomes compared to conventional IT dexamethasone by improving perilymphatic pharmacokinetics, prolonging cochlear retention, and providing synergistic anti-inflammatory and cytoprotective effects via exosome-mediated signaling.

Вмешательства

• Препарат exosomes derived from human umbilical cord mesenchymal stem cells
  Exosomes (30-150 nm) are natural vesicles secreted by most cell types, playing crucial roles in intercellular communication via transport of proteins, lipids, and nucleic acids. As drug delivery vehicles, they offer intrinsic biocompatibility, low immunogenicity, and an innate ability to cross biological barriers.

Первичные конечные точки

• To compare the efficacy of a single course of Intratympanic Exosomes-Dexamethasone versus conventional IT dexamethasone and exosome vehicle alone As measured by the mean change in pure-tone average (PTA; 0.5, 1, 2, 4 kHz) from baseline to the 4-week post [Срок оценки: 6 months]
• Exosomes Efficacy As measured by the mean change in pure-tone average (PTA; 0.5, 1, 2, 4 kHz) from baseline to the 4-week post-treatment endpoint [Срок оценки: within six months]

Критерии участия

Критерии включения

• Adults aged 18-65 years.
• Diagnosis of idiopathic SSNHL (≥30 dB sensorineural loss at three consecutive frequencies) within 14 days of symptom onset.
• Failed initial standard systemic steroid therapy (e.g., oral prednisone 1 mg/kg/day for 7-14 days) or presented with contraindications to systemic steroids.
• Willing and able to provide written informed consent.

Критерии исключения

• Identifiable cause of hearing loss (e.g., acoustic neuroma, Meniere's disease, trauma).
• Pre-existing severe to profound hearing loss in the affected ear.
• Active middle ear infection or tympanic membrane perforation.
• History of autoimmune disease, coagulation disorders, or immunodeficiency.
• Pregnancy or lactation.
• Known hypersensitivity to dexamethasone or components of the exosome formulation.
• Participation in another interventional clinical trial within 30 days.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

Египет · 1 центр

• Kafrelsheikh University — Kafr ash Shaykh

Идентификаторы

NCT: NCT07568184 · EXO-DEX-SSNHL-02

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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