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

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

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 Overview

• Status: Not yet recruiting
• Conditions: Sudden Hearing Loss; Extracellular Vesicles
• Intervention / Treatment: Drug: Standard treatment for sudden deafness+hUC-MSC-sEV-003 at an appropriate dose as determined by stage I trial; Drug: Standard treatment for sudden deafness+dexamethasone; Drug: Tympanic injection of hUC-MSC-sEV-003 (small extracellular vesicles) at low doses; Drug: Tympanic injection of hUC-MSC-sEV-003 (small extracellular vesicles) at moderate doses; Drug: Tympanic injection of hUC-MSC-sEV-003 (small extracellular vesicles) at high doses

• Study Type: Interventional
• Enrollment (Estimated): 9
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Yan Jiang; Phone Number: +86-532-82915920; Email: jiangyanoto@qdu.edu.cn
• Study Contact Backup: Name: Caili Ji; Phone Number: +86-532-82915920; Email: haidecai@163.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • The First Affiliated Hospital of Sun Yat-sen University
      • Contact: Qingling Fu; Phone Number: +8613699726862; Email: fuqingl@mail.sysu.edu.cn
      • Principal Investigator: Qingling Fu
    • Guangzhou, Guangdong, China, 519041
      • Guangdong General Hospital
      • Principal Investigator: Hao Xiong
      • Contact: Hao Xiong; Phone Number: +86 13725130384; Email: xiongh@gdph.org.cn
  • Shandong
    • Qingdao, Shandong, China, 266100
      • The Affiliated Hospital of Qingdao University
      • Contact: Yan Jiang; Phone Number: +86-532-82915920; Email: jiangyanoto@qdu.edu.cn
      • Contact: Caili Ji; Email: haidecai@163.com
      • Principal Investigator: Yan Jiang, MD
    • Tai’an, Shandong, China, 271000
      • he Second Affiliated Hospital of Shandong First Medical University
      • Contact: Deli Wang; Phone Number: +8615621335297; Email: WDLWNY@163.com
      • Principal Investigator: Deli Wang
  • Sichuan
    • Chongqing, Sichuan, China, 401121
      • Chongqing General Hospital
      • Principal Investigator: Wei Yuan
      • Contact: Wei Yuan; Phone Number: +8613368228269; Email: yuanwei@ucas.ac.cn

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Group--Clinical Phase II; Standard treatment for sudden deafness+hUC-MSC-sEV-003 at an appropriate dose as determined by the stage I trial	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.
Experimental: Low-dose Treatment group-Clinical Phase I; Standard treatment for sudden deafness+hUC-MSC-sEV-003 at low-dose treatment in clinical phase I	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.
Experimental: Moderate-dose Treatment Group--Clinical Phase I; Standard treatment for sudden deafness+hUC-MSC-sEV-003 at moderate-dose treatment in clincal phase I	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.
Experimental: High-dose treatment in Clincal Phase I; Standard treatment for sudden deafness+hUC-MSC-sEV-003 at high-dose treatment in clincal phase I	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.
Active Comparator: Control Group--Clinical Phase II; Standard treatment for sudden deafness+dexamethasone injected into the tympanic cavity	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	Baseline,7 days,1 month, and 3 months after clinical phase II treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline, 2 weeks after intratympanic injection in the first-phase clinical
Heart rate	The investigators also monitor vital signs heart rate. The unit of heart rate is beats per minute with the normal range 60 to 100 beats per minute at rest.	Baseline, 2 weeks after intratympanic injection in the first-phase clinical
Oxygen saturation	The investigators also monitor vital signs oxygen saturation. The unit of oxygen saturation is percent with the normal range of 95% to 100%.	Baseline, 2 weeks after intratympanic injection in the first-phase clinical
Blood pressure	The investigators also monitor vital signs blood pressure. The unit of blood pressure is mmHg. The normal range is that the systolic pressure should not exceed 140 mmHg, the diastolic pressure should not exceed 90 mmHg, and the blood pressure level should be no less than 90/60 mmHg.	Baseline, 2 weeks after intratympanic injection in the first-phase clinical
tympanic membrane healing status	The investigators observe the healing status of the eardrum. There are two possible outcomes: the eardrum heals or it does not heal.	Baseline, 2 weeks after intratympanic injection in the first-phase clinical
Haematological index on liver function	The investigators assess the changes in haematological index on liver function and kidney function levels compared to the baseline. The indicators for evaluating liver function include biochemical indicators such as albumin, transaminases, and bilirubin.	Baseline, 2 weeks after intratympanic injection in the first-phase clinical
Haematological index on kidney function	The investigators assess the changes in haematological index on kidney function levels compared to the baseline. The indicators for evaluating kidney function include biochemical parameters such as serum creatinine, urea nitrogen, uric acid, glomerular filtration rate, and urine protein.	Baseline, 2 weeks after intratympanic injection in the first-phase clinical
Tinnitus Handicap Inventory	The assessment of the tinnitus symptoms of the participants is conducted using the Tinnitus Handicap Inventory at both the baseline and different post-treatment periods. This scale classifies tinnitus into four grades as follows: Grade 1 (mild), corresponding to a Tinnitus Handicap Inventory score of 1 to 16. The tinnitus sound is faint and sometimes present, sometimes absent. Grade 2 (moderate), with a Tinnitus Handicap Inventory score of 18 to 36. The tinnitus sound is relatively obvious but generally has a minor impact. Grade 3 (moderately severe), with a Tinnitus Handicap Inventory score of 38 to 56. The tinnitus sound is moderate and begins to cause some interference in daily life. Grade 4 (severe), with a Tinnitus Handicap Inventory score of 58 to 76. A higher score means a worse result.	Baseline,7 days,1 month, and 3 months after clinical phase II treatment
Visual Analogue Scale	The psychological assessment of the participants is carried out using the Visual Analogue Scale.The VAS scoring standard uses a straight line or ruler approximately 10 centimeters long, with the two ends marked as 0 and 10 respectively. 0 indicates no pain, and 10 indicates severe pain. Participants mark the corresponding position according to the degree of pain. 2. Pain grading: 0 indicates no pain; 1-3 indicates mild pain; 4-6 indicates moderate pain; 7-9 indicates severe pain; 10 indicates extreme pain. In this scale，a higher score means a worse result.	Baseline,7 days,1 month, and 3 months after clinical phase II treatment

Collaborators and Investigators

• Sponsor: The Affiliated Hospital of Qingdao University

Study record dates

Study Major Dates

• Study Start (Estimated): February 28, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: December 23, 2025
• First Submitted That Met QC Criteria: February 8, 2026
• First Posted (Actual): February 11, 2026

Study Record Updates

• Last Update Posted (Actual): March 25, 2026
• Last Update Submitted That Met QC Criteria: March 21, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• 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, Sudden
• Other Study ID Numbers: QYFYEC2025-196

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The informed consent form of this study does not include clauses authorizing IPD sharing. As a Phase I/II exploratory study, the data involves sensitive medical information and preliminary research results. To protect participants' privacy and comply with ethical and regulatory requirements, the data will not be shared.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No