Immunological Analysis of Lymph Node Tissue After Intralymphatic Immunotherapy: A Prospective Case Control Study
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- Frequency of treatment-related immune cells in the blood samples sample
研究概览
简要总结
Allergy is a public health problem as more than 20% of western society is affected by it. Symptomatic treatment of allergy suffices with less severe allergy. Patients with more severe allergy should be treated with allergen immunotherapy (AIT). Present options of AIT are efficient but of long duration, associated with side effects and require much time from the patient. With Intralymphatic immunotherapy (ILIT), allergen is injected into the lymph node under ultrasound guidance. ILIT is complete after 3 treatment visits, may be more effective than and may have markedly fewer side effects than presently available methods of AIT.
The investigators plan a randomized, parallel group, open-label, prospective case-control study to assess immunological changes in lymph node and peripheral blood after intralymphatic (ILIT) or subcutaneous (SCIT) immunotherapy with POLVAC.
The intervention consists of one ultrasound-guided injection of allergen into inguinal lymph node or subcutaneous injection 1 cm next to the lymph node. Intervention quality (accuracy of injection) will be assessed by the administering physician during treatment and via video recording on the ultrasound device. Side effects associated with treatment will be recorded by the patients for 3 days after the injection.
The effect of intralymphatic or subcutaneous injection on lymph node tissue and immunoglobulins E and G4 in serum as well as cellular analyses of lymph node tissue and peripheral blood will be determined in samples taken during the trial.
The primary effect parameter is the effect of a single intralymphatic allergen injection on immunological parameters as well as allergen delivery to the lymph node as compared with a single subcutaneous injection.
详细描述
This is a prospective, comparative, clinical open label pilot study. From patients with grass pollen allergy who undergo a pre-seasonal SCIT scheme with Polvac™ Grass+RyeSCIT at the USZ Allergy Unit, 30 patients will be recruited for the study.
Four to six weeks after end of SCIT treatment (at maximal maintenance dose), the patients will be randomized to one out of two treatment groups and receive one additional allergen injection. Both treatment groups receives the same drug, but at different doses and routes of administration. Fifteen patients will be allocated to receive another subcutaneous injection with 0.5 ml (2000 U) Polvac Grass+Rye. The other 15 patients will be allocated to receive an intralymphatic injection of 0.1 ml Polvac Grass+Rye with 400 U allergen. Both SCIT and ILIT injections are performed by ultrasound-guidance as to assure injection into the lymph node (ILIT) or 1 cm next to the lymph node (SCIT).
The FNA of lymph node tissue will be conducted at 2, 6 or 24 hours after allergen injection. At the same time, FNA of a contralateral lymph nodes will be performed as baseline. Venous blood will be sampled at all visits: at baseline as well as after 2, 6 or 24 hours, after 7 days and after 28 days of the allergen ILIT or SCIT. The FNA is performed by ultrasound-guidance.
Drug preparation:
The 1 ml medication vial (4000 U/ml) is shaken for 10 seconds. The head of the vial is disinfected and 0.5 ml (for SCIT) or 0.1 ml (for ILIT) of the medication is drawn into a 1 ml syringe with 23G hypodermic needle assuring no air in the syringe or needle. The medication is used no later than 4 hours after the preparation. Replica of the dose are made if more than one injection is to be performed. The remaining medication is discarded.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients who have seasonal grass-pollen-induced rhinoconjunctivitis as confirmed by patient history and type-1-sensitization to grass-pollen in skin and/or serum.
- •Patients that undergo pre-seasonal short-term scheme with Polvac™ SCIT at the USZ Allergy Unit in autumn and winter 2023 for treatment of allergic rhinoconjunctivitis.
- •Informed Consent as documented by signature.
- •Patients are between 18 and 55 years of age when they sign the informed consent.
排除标准
- •Known or suspected allergy to additives to the study product
- •Known intolerance or allergy to phenol
- •Planned depot steroid injection for treatment of allergic rhinoconjunctivitis
- •Uncontrolled asthma or severe asthma with post bronchodilator FEV1<70%, decided by the investigator
- •Pulmonary disease with post bronchodilator FEV1 < 70 % of predicted
- •Pulmonary disease, perennial or seasonal, with daily use of more than 800 microgram inhaled budesonide/day (or equivalent)
- •Treatment with omalizumab or other biologics for allergy, AD, urticaria or asthma.
- •Allergic reaction within the last 4 days or anaphylaxis within last month before planned ILIT or SCIT injection.
研究组 & 干预措施
Subcutaneous immunotherapy
Subcutaneous injection of grass-rye pollen allergen extract and micro-crystalline tyrosine.
Single dose of 2000 U allergen in 0.5 ml. Dosage form: aqueous suspension.
干预措施: Polvac Grass+Rye (Biological)
Intralymphatic immunotherapy
Subcutaneous injection of grass-rye pollen allergen extract and micro-crystalline tyrosine.
Single dose of 400 U allergen in 0.1 ml. Dosage form: aqueous suspension.
干预措施: Polvac Grass+Rye (Biological)
结局指标
主要结局
Frequency of treatment-related immune cells in the blood samples sample
时间窗: First bleeding on day 0. Second bleeding at 2, 6 or 24 hours post allergen injection. Third and fourth bleeding on days 7 and 28.
Venous blood will be collected at first at baseline (day 0), then 2, 6 or 24 hours after allergen injection depending on the randomization, the on days 7 and 28 post allergen injection. The blood will be analysed by measuring cellular composition in whole blood by mass cytometry (CyTOF). Multiple measurements (ca. 30) will be aggregated and described in a heat map.
Frequency of treatment-related immune cells in the FNA sample
时间窗: At 2, 6 or 24 hours post allergen injection.
An FNA of an inguinal lymph node will be performed at either 2, 6 or 24 hours after allergen injection depending on the individual randomization. The lymph node tissue will be evaluated for changes in cellular composition by mass cytometry (CyTOF). Multiple measurements (ca. 30) will be aggregated and described in a heat map.
次要结局
- Concentration of leucocytes as a function of treatment(Day 0. Then 2, 4 or 24 hours post allergen injection. Then on days 7 and 28.)
- Concentration of allergen-specific antibodies as a function of treatment(Day 0, day 7 and day 28.)