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

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).

Study Overview

• Status: Recruiting
• Conditions: Exosomes; Sensori-Neural Deafness
• Intervention / Treatment: Drug: exosomes derived from human umbilical cord mesenchymal stem cells

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Saad Elzayat, PhD; Phone Number: +201012788746; Email: Samoz9@hotmail.com

Study Locations

• Egypt
  • Egypt
    • Kafr ash Shaykh, Egypt, Egypt, 33155
      • Recruiting
      • Kafrelsheikh University
      • Contact: Haitham Hassan Elfarargy; Phone Number: 002 0473109590; Email: Hitham_Elfarargy@med.kfs.edu.eg
      • Contact: Hussein El-Shirbeny; Phone Number: 002 01012788746; Email: hassien.med_0127@med.kfs.edu.eg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Adults aged 18-65 years.
2. Diagnosis of idiopathic SSNHL (≥30 dB sensorineural loss at three consecutive frequencies) within 14 days of symptom onset.
3. 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.
4. Willing and able to provide written informed consent.

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control Group; Participants treated with dexamethasone	Drug: 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.
Experimental: Intervention Group; participants treated with exosomes	Drug: 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.
Experimental: Intervention Group 2; participants treated with exosomes loaded with dexamethasone	Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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		within six months

Collaborators and Investigators

• Sponsor: Kafrelsheikh University
• Collaborators: National Research Centre, Egypt; Al-Azhar University

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2026
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): August 1, 2027

Study Registration Dates

• First Submitted: April 25, 2026
• First Submitted That Met QC Criteria: May 4, 2026
• First Posted (Actual): May 5, 2026

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: May 4, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Exosomes; SNHL; Dexamethasone
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Otorhinolaryngologic Diseases; Sensation Disorders; Ear Diseases; Hearing Loss; Hearing Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Hearing Loss, Sensorineural
• Other Study ID Numbers: EXO-DEX-SSNHL-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: the final results
• IPD Sharing Time Frame: within 1 year
• IPD Sharing Access Criteria: Scientists in the study field
• IPD Sharing Supporting Information Type: ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No