Clinical Study of Moderate to Severe Persistent Allergic Rhinitis Therapy by Human Umbilical Cord Mesenchymal Stem Cells
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Severity and incidence of adverse events (SIAE) on the day of treatment
研究概览
简要总结
The investigators is now carrying out a clinical study of Umbilical cord Mesenchymal Stem Cells (UCMSCs) in the treatment of Allergic rhinitis (AR). UCMSCs is known to its multilineage differentiation potential, strong proliferation ability, low immunogenicity, convenient material acquisition, and fewer restrictions on ethical and moral issues. The investigators hope to find a novel, minimally invasive, effective and simple treatment for the large number of patients with persistent moderate to severe AR.
详细描述
Allergic rhinitis (AR), is a noninfectious inflammatory disease of nasal mucosa mediated by immunoglobulin E (IgE) antibody and involved in a variety of immune active cells and cytokines after the atopic body is exposed to allergens. The incidence of allergic rhinitis increases as people's living standards improves. It is estimated that about 1.4 billion people worldwide have been affected by the disease. Some patients with moderate to severe AR have no improvement in symptoms after drug treatment, which continues to affect daily life and work. Therefore, these patients urgently needs a new, minimally invasive, effective and simple treatment. Mesenchymal Stem Cells (MSCs) are pluripotent stem cells derived from the mesoderm, which can differentiate into bone, cartilage, fat and other cells. MSCs can also secrete a variety of bioactive molecules, which have the effects of regulating immunity and anti-inflammatory. Based on its immunomodulatory effect, MSCs is gradually becoming a new star in the treatment of allergic diseases. In pre-clinical studies on the treatment of AR, MSCs have shown good therapeutic effect in the treatment of allergic rhinitis.
This study is a prospective, open, single-center clinical study. Participants were recruited into three different dose groups. The cohort size of each dose group was 6 participants. The subjects of each group each will receive one course of treatment with a single injection. Subjects of group 1 will receive 0.5×10^6 cells/kg, with a total volume of 100 ml UCMSCs; group 2 will receive 1.0×10^6 cells/kg; with a total volume of 100 ml UCMSCs; group 3 will receive 2.0×10^6 cells/kg, with a total volume of 100 ml UCMSCs. One month after each injection, the Data and Safety Monitoring Committee (DSMC) will comprehensively evaluate the results of the phased clinical research, and after determining the safety and feasibility of the research, the enrollment of the next phase will start. The subjects will be followed up on the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment. The main outcome measures are the severity and incidence of adverse events. The secondary outcome measures are RQLQ score, VAS score, serum inflammatory factor detection, nasal secretion inflammatory factor detection, nasal function test and nasal endoscopy, etc. In addition, the investigators will also monitor safety indicators such as blood routine, urine routine, liver and kidney function, immunological indicators, tumor markers, etc. At the end of the study, according to the data obtained, the clinical safety and feasibility of intravenous infusion of UCMSCs in the treatment of moderate to severe persistent AR will be evaluated, so as to provide drug dose basis for the next stage of clinical research.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with moderate to severe persistent allergic rhinitis who meet the diagnostic criteria for allergic rhinitis (2015 Tianjin standard);
- •The results of allergen examination showed that the allergen was a single allergy of dust mite;
- •After more than 2 years of antihistamine, nasal glucocorticoid and other drug treatments, the curative effect is poor, and the symptoms seriously affect the patient's life;
- •Age 18-60 years old;
- •The patient refused to receive allergen-specific immunotherapy;
- •The patient is willing to receive stem cell therapy and sign an informed consent.
排除标准
- •The subject is accompanied by sinusitis, asthma and aspirin intolerance;
- •The subjects suffer from severe primary heart, liver, lung, kidney and blood diseases;
- •The subjects suffer from Malignant tumors;
- •The subjects suffer from severe immune diseases;
- •The subjects suffer from mental illness;
- •Female subjects who are or are about to become pregnant, pregnant or breastfeeding;
- •Patients who are participating in other clinical trials;
- •In addition to the above conditions, there are other reasons why researchers believe that they are not suitable to participate in this clinical study.
结局指标
主要结局
Severity and incidence of adverse events (SIAE) on the day of treatment
时间窗: Day 1 of treatment
The assessment was conducted according to the Common Adverse Event Evaluation Standard 4.0 (NCI-CTCAE v4.0) jointly issued by the U.S. Department of Health and Human Services, the National Institutes of Health, and the National Cancer Institute.
24 months SIAE
时间窗: 24 months after treatment
The assessment was conducted according to the Common Adverse Event Evaluation Standard 4.0 (NCI-CTCAE v4.0) jointly issued by the U.S. Department of Health and Human Services, the National Institutes of Health, and the National Cancer Institute.
1 week SIAE
时间窗: 1 week after treatment
The assessment was conducted according to the Common Adverse Event Evaluation Standard 4.0 (NCI-CTCAE v4.0) jointly issued by the U.S. Department of Health and Human Services, the National Institutes of Health, and the National Cancer Institute.
1 month SIAE
时间窗: 1 month after treatment
The assessment was conducted according to the Common Adverse Event Evaluation Standard 4.0 (NCI-CTCAE v4.0) jointly issued by the U.S. Department of Health and Human Services, the National Institutes of Health, and the National Cancer Institute.
3rd day SIAE
时间窗: 3 days after treatment
The assessment was conducted according to the Common Adverse Event Evaluation Standard 4.0 (NCI-CTCAE v4.0) jointly issued by the U.S. Department of Health and Human Services, the National Institutes of Health, and the National Cancer Institute.
6 months SIAE
时间窗: 6 months after treatment
The assessment was conducted according to the Common Adverse Event Evaluation Standard 4.0 (NCI-CTCAE v4.0) jointly issued by the U.S. Department of Health and Human Services, the National Institutes of Health, and the National Cancer Institute.
3 months SIAE
时间窗: 3 months after treatment
The assessment was conducted according to the Common Adverse Event Evaluation Standard 4.0 (NCI-CTCAE v4.0) jointly issued by the U.S. Department of Health and Human Services, the National Institutes of Health, and the National Cancer Institute.
12 months SIAE
时间窗: 12 months after treatment
The assessment was conducted according to the Common Adverse Event Evaluation Standard 4.0 (NCI-CTCAE v4.0) jointly issued by the U.S. Department of Health and Human Services, the National Institutes of Health, and the National Cancer Institute.
次要结局
- Nasal function test(The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.)
- Detection of Serum Interleukin 12P70 (IL-12P70)(The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.)
- RQLQ score(The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.)
- VAS score(The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.)
- U-HCG(The day of enrollment screening, 3 months, 6 months, 12 months, and 24 months after the treatment.)
- Detection of Serum Interferon γ (IFN-γ)(The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.)
- Detection of Serum Interferon α (IFN-α)(The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.)
- Detection of Serum Interleukin 5 (IL-5)(The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.)
- Detection of Serum Interleukin 10 (IL-10)(The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.)
- Detection of Serum Interleukin 17A (IL-17A)(The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.)
- Nasal endoscopy(The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.)
- Detection of Serum Interleukin 1β (IL-1β)(The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.)
- Detection of Serum Interleukin 6 (IL-6)(The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.)
- Detection of inflammatory factor Interleukin 1β (IL-1β) in nasal secretions(The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.)
- Detection of inflammatory factor Interleukin 12P70 (IL-12P70) in nasal secretions(The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.)
- Detection of inflammatory factor Interleukin 17A (IL-17A) in nasal secretions(The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.)
- Detection of inflammatory factor Tumor necrosis factor-α（TNF-α） in nasal secretions(The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.)
- Detection of Serum Interleukin 4 (IL-4)(The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.)
- Detection of inflammatory factor Interferon γ (IFN-γ) in nasal secretions(The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.)
- Detection of Serum Interleukin 2 (IL-2)(The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.)
- Detection of Serum Interleukin 8 (IL-8)(The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.)
- Detection of Serum Tumor necrosis factor-α（TNF-α）(The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.)
- Detection of inflammatory factor Interferon α (IFN-α) in nasal secretions(The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.)
- Detection of inflammatory factor Interleukin 4 (IL-4) in nasal secretions(The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.)
- Detection of inflammatory factor Interleukin 10 (IL-10) in nasal secretions(The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.)
- Detection of inflammatory factor Interleukin 2 (IL-2) in nasal secretions(The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.)
- Detection of inflammatory factor Interleukin 5 (IL-5) in nasal secretions(The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.)
- Detection of inflammatory factor Interleukin 6 (IL-6) in nasal secretions(The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.)
- Detection of inflammatory factor Interleukin 8 (IL-8) in nasal secretions(The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.)