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

Phase 2Not Yet RecruitingNCT07404709

The Affiliated Hospital of Qingdao University18 enrolled

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Interventions

Tympanic injection of hUC-MSC-sEV-003 (small extracellular vesicles) at three different dosesDRUG

In Clinical Phase I, nine participants were additionally injected with small extracellular vesicles at three different doses (low to high concentration，3 participants for each dose) 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.

Standard treatment for sudden deafness+hUC-MSC-sEV-003 mimeticsDRUG

In Clinical Phase I, on the basis of receiving standard treatment for sudden deafness, participants were respectively administered intratympanic injections of hUC-MSC-sEV-003 mimics every other day, with each injection volume being 0.5 ml, for a total of three times.

Standard treatment for sudden deafness+hUC-MSC-sEV-003 at an appropriate dose as determined by stage I trialDRUG

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.

Standard treatment for sudden deafness+dexamethasoneDRUG

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. 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. 2. Enrollment must be completed within 7 days after the onset of sudden deafness. 3. Men or women aged 18 to 65 4. Not treated in any other hospital and not taking any treatment medication on one's own 5. Be able to understand the trial protocol and undergo regular follow-up visits and check-ups Exclusion Criteria: 1. Pregnant or lactating women 2. With a history of chronic ear diseases, ear surgery, autoimmune hearing loss or a confirmed diagnosis of Meniere's syndrome in the past 3. Having received steroid treatment for any reason within the past 30 days 4. There are autoimmune diseases or chronic inflammatory diseases. 5. Severe damage to liver and kidney functions 6. Patients with a previous history of cerebral hemorrhage or those currently taking anticoagulant medications 7. Other cases in which the researchers judged the candidates to be unsuitable for inclusion

Locations (5)

The First Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, China

Guangdong General Hospital

Guangzhou, Guangdong, China

The Affiliated Hospital of Qingdao University

Qingdao, Shandong, China

he Second Affiliated Hospital of Shandong First Medical University

Tai’an, Shandong, China

Chongqing General Hospital

Chongqing, Sichuan, China

Outcomes

Primary Outcomes

Pure tone test

The hearing recovery status is evaluated based on the changes in pure tone threshold from the baseline at enrollment to 3 months of follow-up. The pure tone threshold is the average of air conduction thresholds at 0.25, 0.5, 1, 2, 4 kHz, and 8 kHz.

Time frame: Baseline,7 days,1 month, and 3 months after clinical phase II treatment

speech audiometry

The hearing recovery status is also evaluated based on the changes in speech recognition rate from the baseline at enrollment to 3 months of follow-up. The speech audiometry results use the speech recognition rates at the baseline and after treatment of the subjects.

Time frame: Baseline,7 days,1 month, and 3 months after clinical phase II treatment

Secondary Outcomes

Respiration

The investigators monitor vital signs respiration. The unit of respiratory rate is breaths per minute with the normal range 12 to 20 beats per minute.