Clinical trial NCT05151133: Clinical Study of Allergic Rhinitis Therapy by Stem Cells
Official title: Clinical Study of Moderate to Severe Persistent Allergic Rhinitis Therapy by Human Umbilical Cord Mesenchymal Stem Cells
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Allergic Rhinitis
Keywords: Umbilical cord
Mesenchymal Stem Cells
Allergic Rhinitis
Therapy
Lead sponsor: Yantai Yuhuangding Hospital
Sponsor class: OTHER
First posted: 2021-12-09
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Patients with moderate to severe persistent allergic rhinitis who meet the diagnostic criteria for allergic rhinitis (2015 Tianjin standard);
2. The results of allergen examination showed that the allergen was a single allergy of dust mite;
3. 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;
4. Age 18-60 years old;
5. The patient refused to receive allergen-specific immunotherapy;
6. The patient is willing to receive stem cell therapy and sign an informed consent.

Exclusion Criteria:

1. The subject is accompanied by sinusitis, asthma and aspirin intolerance;
2. The subjects suffer from severe primary heart, liver, lung, kidney and blood diseases;
3. The subjects suffer from Malignant tumors;
4. The subjects suffer from severe immune diseases;
5. The subjects suffer from mental illness;
6. Female subjects who are or are about to become pregnant, pregnant or breastfeeding;
7. Patients who are participating in other clinical trials;
8. In addition to the above conditions, there are other reasons why researchers believe that they are not suitable to participate in this clinical study.

Primary outcomes:
measure: Severity and incidence of adverse events (SIAE) on the day of treatment
timeFrame: Day 1 of treatment
measure: 3rd day SIAE
timeFrame: 3 days after treatment
measure: 1 week SIAE
timeFrame: 1 week after treatment
measure: 1 month SIAE
timeFrame: 1 month after treatment
measure: 3 months SIAE
timeFrame: 3 months after treatment
measure: 6 months SIAE
timeFrame: 6 months after treatment
measure: 12 months SIAE
timeFrame: 12 months after treatment
measure: 24 months SIAE
timeFrame: 24 months after treatment
Secondary outcomes:
measure: RQLQ score
timeFrame: The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.
measure: VAS score
timeFrame: The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.
measure: Nasal function test
timeFrame: The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.
measure: Nasal endoscopy
timeFrame: The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.
measure: U-HCG
timeFrame: The day of enrollment screening, 3 months, 6 months, 12 months, and 24 months after the treatment.
measure: Detection of Serum Interferon γ (IFN-γ)
timeFrame: The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.
measure: Detection of Serum Interferon α (IFN-α)
timeFrame: The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.
measure: Detection of Serum Interleukin 1β (IL-1β)
timeFrame: The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.
measure: Detection of Serum Interleukin 2 (IL-2)
timeFrame: The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.
measure: Detection of Serum Interleukin 4 (IL-4)
timeFrame: The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.
measure: Detection of Serum Interleukin 5 (IL-5)
timeFrame: The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.
measure: Detection of Serum Interleukin 6 (IL-6)
timeFrame: The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.
measure: Detection of Serum Interleukin 8 (IL-8)
timeFrame: The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.
measure: Detection of Serum Interleukin 10 (IL-10)
timeFrame: The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.
measure: Detection of Serum Interleukin 12P70 (IL-12P70)
timeFrame: The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.
measure: Detection of Serum Interleukin 17A (IL-17A)
timeFrame: The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.
measure: Detection of Serum Tumor necrosis factor-α（TNF-α）
timeFrame: The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.
measure: Detection of inflammatory factor Interferon γ (IFN-γ) in nasal secretions
timeFrame: The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.
measure: Detection of inflammatory factor Interferon α (IFN-α) in nasal secretions
timeFrame: The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.
measure: Detection of inflammatory factor Interleukin 1β (IL-1β) in nasal secretions
timeFrame: The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.
measure: Detection of inflammatory factor Interleukin 2 (IL-2) in nasal secretions
timeFrame: The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.
measure: Detection of inflammatory factor Interleukin 4 (IL-4) in nasal secretions
timeFrame: The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.
measure: Detection of inflammatory factor Interleukin 5 (IL-5) in nasal secretions
timeFrame: The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.
measure: Detection of inflammatory factor Interleukin 6 (IL-6) in nasal secretions
timeFrame: The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.
measure: Detection of inflammatory factor Interleukin 8 (IL-8) in nasal secretions
timeFrame: The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.
measure: Detection of inflammatory factor Interleukin 10 (IL-10) in nasal secretions
timeFrame: The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.
measure: Detection of inflammatory factor Interleukin 12P70 (IL-12P70) in nasal secretions
timeFrame: The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.
measure: Detection of inflammatory factor Interleukin 17A (IL-17A) in nasal secretions
timeFrame: The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.
measure: Detection of inflammatory factor Tumor necrosis factor-α（TNF-α） in nasal secretions
timeFrame: The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.
Other outcomes:
measure: Blood routine
timeFrame: The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.
measure: Urine routine
timeFrame: The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.
measure: Liver and kidney function
timeFrame: The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.
measure: Immunological indicators
timeFrame: The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.
measure: Tumor markers
timeFrame: The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.
measure: Total Protein Concentration of Nasal Secretions
timeFrame: The day of enrollment screening, the 3rd day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after the treatment.
Locations:
city: Yantai
country: China
facility: Yantai Yuhuangding Hospital
state: Shandong
Study officials:
affiliation: Yantai Yuhuangding Hospital
name: Xicheng Song, MD
role: PRINCIPAL_INVESTIGATOR
References: