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).
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
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.
Type d'étude
Inscription (Estimé)
Phase
- N'est pas applicable
Contacts et emplacements
Coordonnées de l'étude
- Nom: Saad Elzayat, PhD
- Numéro de téléphone: +201012788746
- E-mail: Samoz9@hotmail.com
Lieux d'étude
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Egypt
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Kafr ash Shaykh, Egypt, Egypte, 33155
- Recrutement
- Kafrelsheikh University
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Contact:
- Haitham Hassan Elfarargy
- Numéro de téléphone: 002 0473109590
- E-mail: Hitham_Elfarargy@med.kfs.edu.eg
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Contact:
- Hussein El-Shirbeny
- Numéro de téléphone: 002 01012788746
- E-mail: hassien.med_0127@med.kfs.edu.eg
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
- Adulte
- Adulte plus âgé
Accepte les volontaires sains
La description
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 d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Tripler
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
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Comparateur actif: 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.
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|
Expérimental: 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.
|
|
Expérimental: 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.
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
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
Délai: 6 months
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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
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6 months
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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
Délai: within six months
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within six months
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Collaborateurs et enquêteurs
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Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- EXO-DEX-SSNHL-02
Plan pour les données individuelles des participants (IPD)
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Description du régime IPD
Délai de partage IPD
Critères d'accès au partage IPD
Type d'informations de prise en charge du partage d'IPD
- CIF
- RSE
Informations sur les médicaments et les dispositifs, documents d'étude
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