Autologous Blood Monocyte Vesicles for the Treatment of Sudden Deafness

A Pilot Study of Autologous Blood Monocyte Vesicles for the Treatment of Sudden Deafness

Sudden deafness is a common emergency in otorhinolaryngology. As the etiology and mechanism of sudden deafness remains unknown, there is no specific treatment. Therefore, to explore new treatments for sudden deafness is a urgent and challenging problem. Extracellular vesicles therapy has been proved to be effective for several diseases. From our previous study, extracellular vesicles from mesenchymal stem cell can effectively improve noise-induced sensorineural deafness in mice. While mesenchymal stem cell therapy faces immune rejection in clinical use, the investigators use autologous blood monocyte vesicles to avoid immune rejection and guarantee patients' safety. In this interventional study, the investigators aimed to study the clinical effects and adverse reactions of autologous blood monocyte vesicle therapy in the treatment of sudden deafness. A total of 30 patients with severe or worse sudden deafness will enroll in this study and randomly assigned to 3 group, which are control group (Intratympanic glucocorticoid injection), lower-dose apoVs group (lower dose of Intratympanic monocyte vesicles injection) and higher-dose apoVs group (higher dose of Intratympanic monocyte vesicles injection). This study will further promote new treatment for sudden deafness and improve the quality of life and prognosis of patients with sudden deafness, especially those with severe or extremely severe deafness.

Study Overview

• Status: Not yet recruiting
• Conditions: Sensorineural Hearing Loss; Sudden Deafness
• Intervention / Treatment: Drug: Methylprednisolone; Biological: autologous blood monocyte vesicles (lower dose); Biological: autologous blood monocyte vesicles (higher dose)

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Yang Haidi, Doctor; Phone Number: 13178821663; Email: yanghd@mail.sysu.edu.cn
• Study Contact Backup: Name: Huang Xiaotong; Email: huangxt26@mail2.sysu.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients aged between 18 and 65.
• Patients with severe and above unilateral hearing loss who meet the diagnostic criteria for sudden deafness.
• Patients who suffer sudden deafness within 3 weeks and do not receive intratympanic injection.
• Patients who fully understand the purpose and requirements of the trial, volunteer to participate in the clinical trial, sign a written informed consent, and is willing to complete the whole trial process according to the trial requirements.

Exclusion Criteria:

• Patients with conductive deafness and mixed deafness;
• Patients with other otologic diseases;
• Those who have doubts about the treatment plan or have obvious mental and psychological disorders;
• Patients with severe heart, lung, liver and kidney dysfunction;
• Patients with severe hematological diseases or tumors (especially those with acoustic neuromas);
• Those with positive HIV antibody, HBsAg, HCV antibody, or serological examination results for syphilis;
• Patients with a history of infection within 1 month prior to screening, requiring hospitalization and / or antibiotics, or currently using systemic hormones (corticosteroids), immunosuppressants or cytotoxicity;
• Patients with a history of immune system diseases or hematological system diseases;
• Patients with abnormal blood findings, such as abnormal number and morphology of red blood cells, white blood cells and platelets;
• Patients with severe or unstable cardiovascular, respiratory, liver, kidney, blood, endocrine, and central nervous system diseases;
• Women during lactation, pregnancy, or possibly pregnancy;
• Patients with contraindications or allergies to the treatment of this study;
• Those who have participated in any clinical drug trial in the past 3 months;
• Patients that the Investigator considers unsuitable to participate in the trial;
• Patients not suitable for tympanic injection therapy.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: control; Intratympanic injection of methylprednisolone (methylprednisolone succinic acid for injection) at a dose of 40mg/mL, three times a week. 40mg of methylprednisolone was dissolved in 0.2 ml of lidocaine injection and 0.8 ml of sterilized injection water.	Drug: Methylprednisolone; 40mg of methylprednisolone was dissolved in 0.2 ml of lidocaine injection and 0.8 ml of sterilized injection water. Intratympanic injection of methylprednisolone was performed three times a week.
Experimental: apoVs(lower dose); Intratympanic injection of autologous blood monocyte vesicles, three times a week. Autologous blood monocyte vesicles were extracted from 20 ml peripheral blood from patients and dissolved in 0.2 ml of lidocaine injection and 0.8 ml of sterilized injection water.	Biological: autologous blood monocyte vesicles (lower dose); 20 ml peripheral venous blood was extracted from each patient, anticoagulated with heparin and diluted with PBS. Peripheral blood mononuclear cells were isolated by Ficoll stratified solution. Extracellular vesicles of mononuclear cells were extracted by gradient centrifugation (800g centrifugation at 4 ℃ for 10 minutes, then 2000g centrifugation at centrifuged at 4 ℃ for 10 minutes and then 16000g centrifugation at 4 ℃ for 30 minutes. The precipitate was taken as monocyte vesicle and stored in refrigerator at 4 ℃. For intratympanic injection, precipitate was dissolved in 0.2 ml of lidocaine and 0.8 ml of sterilized injection water. Intratympanic injection of apoVs was performed three times a week.
Experimental: apoVs(higher dose); Intratympanic injection of autologous blood monocyte vesicles, three times a week. Autologous blood monocyte vesicles were extracted from 50 ml peripheral blood from patients and dissolved in 0.2 ml of lidocaine injection and 0.8 ml of sterilized injection water.	Biological: autologous blood monocyte vesicles (higher dose); 50 ml peripheral venous blood was extracted from each patient, anticoagulated with heparin and diluted with PBS. Peripheral blood mononuclear cells were isolated by Ficoll stratified solution. Extracellular vesicles of mononuclear cells were extracted by gradient centrifugation (800g centrifugation at 4 ℃ for 10 minutes, then 2000g centrifugation at centrifuged at 4 ℃ for 10 minutes and then 16000g centrifugation at 4 ℃ for 30 minutes. The precipitate was taken as monocyte vesicle and stored in refrigerator at 4 ℃. For intratympanic injection, precipitate was dissolved in 0.2 ml of lidocaine and 0.8 ml of sterilized injection water. Intratympanic injection of apoVs was performed three times a week.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Audiometry	Pure tone audiometry.	4 weeks after intervention.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Audiometry	Pure tone audiometry	1 week, 2 weeks after intervention
THI scale	THI (tinnitus handicap inventory) is one of the most widely used tinnitus self-rating scales in the world.It consists of three dimensions: functional, emotional and severity and effect of decreased tinnitus on patients' daily life. The THI score is totally 100 points. The more score participants get, the severer tinnitus symtoms they suffer from. According to the total score, paticipants were divided into five grades, Grade I (0-16, light) , Grade II (18-36, mild) , Grade III (38-56, moderate) , grade IV (58-76, severe) , grade V (78-100, catastrophic).	1 week, 2 weeks, 4 weeks after intervention.
Tinnitus VAS	The VAS(visual analogue scale) for subjective severity of tinnitus focuses on the subjective assessment of general sensation. The VAS has a scale score of 0 to 10, with 0 being completely unaffected and 10 being very severely affected.	1 week, 2 weeks, 4 weeks after intervention.
SAS	The SAS(Self-Rating Anxiety Scale) consists of 20 items which reflect the subjective and feeling of Anxiety. The more score paticipants get, the more anxiety they suffer. The SAS score can be divided into 4 levels: normal(less than 50 score), mild anxiety(50-59 score), moderate anxiety(60-69 score) and severe anxiety(more than 69 score).	1 week, 2 weeks, 4 weeks after intervention.
Adverse Events	Local adverse events include hearing loss, otitis media, and unperforation of tympanic membrane. Systemic adverse events include vital signs instability, new-onset anemia, liver and kidney dysfunction and so on. The severity of adverse events was graded according to the Common Adverse Event Evaluation Criteria (CTCAE) 5.0, Grade 1: mild; asymptomatic or mild; clinical or diagnostic only; treatment free. Grade 2: Moderate; requiring small, local, or non-invasive treatment; limited instrumental daily living activities comparable to age. Grade 3: serious or medically significant but not immediately life threatening; hospitalization or prolonged hospitalization; disability; limited activities of daily life. Grade 4: life-threatening; requiring urgent treatment. Grade 5: Death related to AEs.	1 week, 2 weeks, 4 weeks after intervention.

Collaborators and Investigators

• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Study record dates

Study Major Dates

• Study Start (Estimated): December 25, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: July 11, 2024
• First Submitted That Met QC Criteria: November 26, 2024
• First Posted (Actual): November 27, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 24, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Otorhinolaryngologic Diseases; Sensation Disorders; Ear Diseases; Hearing Disorders; Hearing Loss; Deafness; Hearing Loss, Sensorineural; Hearing Loss, Sudden; Antineoplastic Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protective Agents; Neuroprotective Agents; Methylprednisolone Acetate; Prednisolone; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate
• Other Study ID Numbers: SYSKY-2023-1250-02

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