Clinical Study of the Safety and Efficacy of Umbilical Cord Mesenchymal Stem Cell Exosomes in Treating Chronic Cough After COVID-19 Infection
试验速览
- 阶段
- 早期 1 期
- 状态
- 招募中
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Cough Evaluation Test
研究概览
简要总结
This clinical trial aims to evaluate the safety and effectiveness of umbilical cord mesenchymal stem cell (UCMSC)-derived extracellular vesicle nebulization inhalation therapy for the treatment of chronic cough after COVID-19 infection. The main objective is to assess whether UCMSC-derived exosome nebulization inhalation therapy alleviates chronic cough after COVID-19.
Participants will be asked to complete a questionnaire to help researchers evaluate their cough severity and to record their scores before nebulization inhalation of UCMSC-derived exosomes. Participants will receive either continuous nebulized inhalation of UCMSC-derived exosomes for 5 days, twice daily, or no treatment. Researchers will compare the experimental and control groups to evaluate the safety and efficacy of UCMSC-derived exosomes for the treatment of chronic cough after COVID-19 infection.
详细描述
- Background 1.1 Post-COVID-19 Syndrome, also known as Long Covid, is still causing great trouble to the public despite China having successfully passed the first wave of infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for over three years, which has resulted in over 5 million deaths globally.
Long Covid is a multiple-system disease that includes a variety of severe symptoms that persist after infection with COVID-19, such as (1) heart-related symptoms: chest pain, palpitations; (2) respiratory symptoms: cough, shortness of breath, loss of taste or smell; (3) pancreatic symptoms: diabetes, pancreatic injury; (4) immune system: autoimmunity, mast cell activation syndrome MCAS; (5) neurological symptoms: cognitive impairment (brain fog), fatigue, sleep disorders, memory loss, tinnitus; (6) vascular symptoms: fatigue, coagulation disorders, deep vein thrombosis, endothelial dysfunction, microvascular disease, stroke; (7) reproductive symptoms: erectile dysfunction, menstrual disorders, etc., which severely affect the patient's daily life. Long Covid can occur in people of all ages, and the likelihood of developing it is closely related to the severity of acute COVID-19 infection. The main high-risk factors that can trigger Long Covid include (1) type II diabetes, (2) high viral load during COVID-19 infection, (3) previous infection with EB virus, and (4) excessive specific autoantibodies. Treatment strategies for COVID-19 mainly involve using antiviral drugs to block the replication cycle of the virus and various methods to suppress host inflammation to improve symptoms. Currently, the conventional immunotherapy methods used in clinics mainly involve the use of hormones, monoclonal antibody drugs, etc., but they are mainly targeted at more severe inflammatory reactions and suffer from low bioavailability, high cost, and significant side effects, making them unsuitable for the treatment of long COVID. Therefore, developing new immune-regulating methods with low side effects and costs would be significant for the treatment of long COVID.
1.2 Mesenchymal stem cells (MSCs) MSCs have been shown to have comprehensive and powerful immune-regulatory and regenerative functions. MSCs can counteract cell death related to the pathogenesis of chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis, asthma, ARDS, and pulmonary hypertension, and promote cell regeneration. Exosomes are one of the key paracrine effectors secreted by MSCs, and they are considered powerful candidates for alternative treatment of various diseases because their biological material is like that of progenitor cells, and they have the ability to maintain healing properties. Under physiological and pathological conditions, exosomes play a critical role in intercellular communication by transporting various biomolecules (such as miRNA and proteins) into target cells.
1.3 the mechanism of MSC-derived exosomes MSC-derived exosomes inherit immunosuppressive properties from their source cells. MSC-EVs may use multiple mechanisms to balance the function of the immune system. One key mechanism is reprogramming and changing the phenotype of various immune cells.
In multiple models, MSC-exosomes have therapeutic properties similar to MSCs and are easier to prepare, store, and transport to the bedside, while avoiding some limitations of cell therapy, such as the risk of pulmonary embolism and tumor formation. Exosomes secreted by MSCs can regulate immunity through an interaction with immune cells and inhibit inflammatory reactions through cytokines. Numerous studies have shown that exosomes secreted by MSCs can be used to treat immunodeficiency, inflammation, ARDS, and other lung diseases, so exosomes secreted by MSCs may also be effective in treating COVID-19 infections and pneumonia. The conventional method of stem cell therapy is an intravenous injection, and exosomes are one of the main active components secreted by stem cells with a size of 30-150 nm. After nebulization, exosomes can directly reach the bronchioles and alveoli, which is conducive to maximizing drug absorption.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Investigator)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Trial participants voluntarily participate in this study and sign an informed consent form.
- •At the time of signing the informed consent form, the age of the subject should be ≥18 or ≤80 years old, with no gender restrictions.
- •The subject has been diagnosed with COVID-19 (confirmed by positive nucleic acid or antigen test) and has symptoms that have lasted for more than 4 weeks.
- •Negative nucleic acid or antigen test at the time of screening.
- •The subject has had continuous or intermittent coughing, or loss of taste/smell for ≥4 weeks, which did not occur before the onset of COVID-19 infection.
- •No prior treatment with umbilical cord mesenchymal stem cell-derived extracellular vesicles.
- •The patient fully understands the purpose and requirements of this clinical study and is willing to complete all trial procedures according to the study requirements.
排除标准
- •Age ≤18 or ≥80 years old.
- •Acute COVID-19 patients.
- •Suspected or confirmed to have severe, active bacterial, fungal, or other infections that may pose a risk when intervention measures are taken, as determined by the researcher.
- •Patients with a history of diagnosed bronchial asthma, cough variant asthma, or chronic cough; patients with other pulmonary diseases such as chronic obstructive pulmonary disease, bronchiectasis, tuberculosis, lung cancer, etc.
- •Any of the following during the screening period: 1) ALT or AST > 3 times the upper limit of normal; 2) eGFR <60 mL/min.
- •Patients with a history of severe allergies.
- •Patients with uncontrolled severe cardiovascular, cerebrovascular, liver, kidney, endocrine, blood system diseases, and mental illness.
- •Patients with active immunosuppression, immunodeficiency, and use of immunosuppressive drugs.
- •Pregnant and lactating women.
- •Other factors that the researcher deems unsuitable for participation in the study based on clinical considerations.
结局指标
主要结局
Cough Evaluation Test
时间窗: 6-14days
This score is to evaluate the relief of cough symptoms. Higher scores mean worse outcome. Minimum score is 5, maximum score is 25.
次要结局
- Improvement or relief time of symptoms(6th, 15th, 28th day)
研究者
Jihui Du
Professor
Huazhong University of Science and Technology