Study on the Safety and Efficacy of Intratympanic Injection of Small Extracellular Vesicles Derived From Mesenchymal Stem Cells in Severe and Profound Sudden Sensorineural Hearing Loss

Official title

Clinical Phase I and IIa Trials of Intratympanic Injection of Small Extracellular Vesicles Derived From Mesenchymal Stem Cells in Severe and Profound Sudden Sensorineural Hearing Loss

Overview

The goal of this clinical trial is to learn if small extracellular vesicles derived from mesenchymal stem cells work to treat severe and above sudden sensorineural hearing loss. It will also learn about the safety of small extracellular vesicles. The main questions it aims to answer are: 1. Does small extracellular vesicles combined with traditional drug treatment improve hearing even better in severe and above sudden deafness participants? 2. What medical problems do participants have with intratympanic injection of small extracellular vesicles? Researchers will compare small extracellular vesicles to dexamethasone to see if small extracellular vesicles work to treat severe and above sudden sensorineural hearing loss. In clinical Phase I trial, the investigators will complete the safety check and dose exploration. Participants will: 1. Receive traditional drug treatment in accordance with the "Guidelines for the Diagnosis and Treatment of Sudden Deafness (2015) 2. Receive small extracellular vesicles or a placebo tympanic injection additionally 3. Visit the clinic once every 2 weeks for checkups and tests 4. Receive tympanic injections of small extracellular vesicles ranging from low concentration to high concentration 5. Be evaluated for any adverse reactions In clinical Phase II trial, participants were randomly divided into a control group and an experimental group. Participants will: 6. Received intratympanic injections of small extracellular vesicles 3 times together with traditional drug treatment in experimental group 7. Received intratympanic injections of 5mg dexamethasone 3 times together with traditional drug treatment in control group, also for a total of 3 times Visit the clinic once 7 days , 1month and 3 months after treatment for checkups and tests of pure tone audiometry, speech audiometry, tinnitus disability scale and visual analogue scale assessment

Interventions

• Drug Tympanic injection of hUC-MSC-sEV-003 (small extracellular vesicles) at low doses
  In Clinical Phase I, three participants were first injected with small extracellular vesicles at low doses (2×108particles/mL) together with traditional drug treatment. The intratympanic injection of small extracellular vesicles was given every other day for a total of 3 times for every participants.
• Drug Tympanic injection of hUC-MSC-sEV-003 (small extracellular vesicles) at moderate doses
  In Clinical Phase I, if no adverse reactions were observed for 2 weeks after the low-dose group was injected, three participants were then injected with small extracellular vesicles at moderat doses (1×109particles/mL) together with traditional drug treatment. The intratympanic injection of small extracellular vesicles was given every other day for a total of 3 times for every participants.
• Drug Tympanic injection of hUC-MSC-sEV-003 (small extracellular vesicles) at high doses
  n Clinical Phase I, if no adverse reactions were observed for 2 weeks after the moderate-dose group was injected, three participants were then injected with small extracellular vesicles at high doses (5×109particles/mL) together with traditional drug treatment. The intratympanic injection of small extracellular vesicles was given every other day for a total of 3 times for every participants.
• Drug Standard treatment for sudden deafness+hUC-MSC-sEV-003 at an appropriate dose as determined by stage I trial
  After the safety verification and dose determination of the Phase I clinical trial were completed, about 20 participants received standard treatment in accordance with the "Guidelines for the Diagnosis and Treatment of Sudden Deafness (2015)", and at the same time, they were administered intratympanic injections of small extracellular vesicles every other day, for a total of 3 times.
• Drug Standard treatment for sudden deafness+dexamethasone
  Participants in the control group received standard treatment in accordance with the "Guidelines for the Diagnosis and Treatment of Sudden Deafness (2015)", and during their hospitalization, they received intratympanic injections of dexamethasone at a dose of 5mg every other day for a total of 3 times.

Primary outcome measures

• Pure tone test [Time frame: Baseline,7 days,1 month, and 3 months after clinical phase II treatment]
• speech audiometry [Time frame: Baseline,7 days,1 month, and 3 months after clinical phase II treatment]

Secondary outcome measures (9)

• Respiration [Time frame: Baseline, 2 weeks after intratympanic injection in the first-phase clinical]
• Heart rate [Time frame: Baseline, 2 weeks after intratympanic injection in the first-phase clinical]
• Oxygen saturation [Time frame: Baseline, 2 weeks after intratympanic injection in the first-phase clinical]
• Blood pressure [Time frame: Baseline, 2 weeks after intratympanic injection in the first-phase clinical]
• tympanic membrane healing status [Time frame: Baseline, 2 weeks after intratympanic injection in the first-phase clinical]
• Haematological index on liver function [Time frame: Baseline, 2 weeks after intratympanic injection in the first-phase clinical]
• Haematological index on kidney function [Time frame: Baseline, 2 weeks after intratympanic injection in the first-phase clinical]
• Tinnitus Handicap Inventory [Time frame: Baseline,7 days,1 month, and 3 months after clinical phase II treatment]
• Visual Analogue Scale [Time frame: Baseline,7 days,1 month, and 3 months after clinical phase II treatment]

Eligibility criteria

Inclusion criteria

• Sudden unilateral hearing loss that occurs within 72 hours, with a decrease of at least 30 decibels in at least 3 frequency ranges compared to the healthy ear, and an average pure tone threshold of ≥ 65 decibels.
• Enrollment must be completed within 7 days after the onset of sudden deafness.
• Men or women aged 18 to 65
• Not treated in any other hospital and not taking any treatment medication on one's own
• Be able to understand the trial protocol and undergo regular follow-up visits and check-ups

Exclusion criteria

• Pregnant or lactating women
• With a history of chronic ear diseases, ear surgery, autoimmune hearing loss or a confirmed diagnosis of Meniere's syndrome in the past
• Having received steroid treatment for any reason within the past 30 days
• There are autoimmune diseases or chronic inflammatory diseases.
• Severe damage to liver and kidney functions
• Patients with a previous history of cerebral hemorrhage or those currently taking anticoagulant medications
• Other cases in which the researchers judged the candidates to be unsuitable for inclusion

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

China · 5 centers

• The First Affiliated Hospital of Sun Yat-sen University — Guangzhou
• Guangdong General Hospital — Guangzhou
• The Affiliated Hospital of Qingdao University — Qingdao
• he Second Affiliated Hospital of Shandong First Medical University — Tai’an
• Chongqing General Hospital — Chongqing

Identifiers

NCT: NCT07404709 · QYFYEC2025-196

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗