A Randomized Trial of Intratympanic Drug Delivery: Evaluating the Efficacy and Safety of Dexamethasone-Loaded Exosomes Versus Standard Therapy in Acute Sensorineural Hearing Loss. (EXO-DEX-SNHL)
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.
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
- To determine the safety and tolerability profile of IT Exo-Dex.
- 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.
- To assess changes in auditory function via Auditory Brainstem Response (ABR) thresholds and Otoacoustic Emissions (OAEs).
- 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).
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
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.
Tipo de estudio
Inscripción (Estimado)
Fase
- No aplica
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Saad Elzayat, PhD
- Número de teléfono: +201012788746
- Correo electrónico: Samoz9@hotmail.com
Ubicaciones de estudio
-
-
Egypt
-
Kafr ash Shaykh, Egypt, Egipto, 33155
- Reclutamiento
- Kafrelsheikh University
-
Contacto:
- Haitham Hassan Elfarargy
- Número de teléfono: 002 0473109590
- Correo electrónico: Hitham_Elfarargy@med.kfs.edu.eg
-
Contacto:
- Hussein El-Shirbeny
- Número de teléfono: 002 01012788746
- Correo electrónico: hassien.med_0127@med.kfs.edu.eg
-
-
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Descripción
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Triple
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Comparador activo: Control Group
Participants treated with dexamethasone
|
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.
|
|
Experimental: Intervention Group
participants treated with exosomes
|
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.
|
|
Experimental: Intervention Group 2
participants treated with exosomes loaded with dexamethasone
|
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.
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
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
Periodo de tiempo: 6 months
|
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
|
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
Periodo de tiempo: within six months
|
within six months
|
Colaboradores e Investigadores
Patrocinador
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- EXO-DEX-SSNHL-02
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan IPD
Marco de tiempo para compartir IPD
Criterios de acceso compartido de IPD
Tipo de información de apoyo para compartir IPD
- CIF
- RSC
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
producto fabricado y exportado desde los EE. UU.
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .