Changes in Adaptive Immune Responses and Effector Cell Responses Upon Nasal Allergen Exposure - a Pilot Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 2
- 主要终点
- Allergen Specific IgE Rise
研究概览
简要总结
IgE-associated allergy is a hypersensitivity disease affecting more than 25% of the population in industrialised countries. The recognition of allergen by immunoglobulin E (IgE) plays a central role in the cause of allergic diseases. Both seasonal and nasal provocation studies have demonstrated the rise in specific IgE after allergen exposure. Additionally changes in other clinical and immunological parameters (e.g. nasal blockage, mast cell and basophil sensitivity, various cytokines or T cell profiles) in response to allergen exposure have been described. However the time sensitive interplay of these various factors such as the relationship between rise in IgE levels and change in basophils sensitivity or cytokine profiles is not yet fully understood. Clarifying how these various factors interact and contribute to immunological responses to allergen, is crucial for the development of new therapeutic approaches.
The investigators aim to address these questions through a study following 36 Birch allergic patients after provocation with allergen or placebo over a peroid of 6 weeks to 1 year.
详细描述
Rational of the Study
Previous studies on the dynamics of the in vivo clinical and immunological responses to nasal allergen have focused on particular parameters but have not addressed the kinetics of the interplay between the different factors (i.e. allergen-specific IgE levels, local IgE and mediator production, basophil sensitivity, cutaneous sensitivity). The investigators therefore propose a randomized double-blind placebo controlled study where The investigators challenge patients intranasally with allergen extract and then closely monitor both clinical and immunological immune responses over a period of 4 months. After this a further 4 visits will take place before and after the birch season.
The investigators will look at immediate and late phase immune responses to birch pollen extract nasal challenge outside the pollen season. Study participants will initially undergo 3 consecutive days of nasal allergen challenge and then be closely followed up for a period of 1 year. To assess clinical response to allergen exposure, The investigators will make use of the skin prick test (SPT), total nasal symptom score (TNSS), nasal endoscopy and Peak Inspiratory Nasal Flow Meter (PNIF). To assess immunological responses samples including blood, nasal mucosal sampling and nasal secretions will be taken.
Study Design
In this single-center, randomized, placebo-controlled, double-blind study a total of 36 (6 for a pre study) patients will be recruited into this study on a voluntary basis and will be randomised to receive a nasal challenge with either birch pollen extract or placebo. Randomisation will be stratified according to Bet v 1 specific IgE levels to allow for equal distribution in both groups. 30 Study participants will receive nasal provocation outside of the birch pollen season with either birch pollen extract or placebo on three consecutive days and will thereafter be followed up at a regular basis for up to four months.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male or female
- •18 to 60 years of age
- •Birch pollen sensitized subjects
- •Moderate to severe allergic rhinitis to birch pollen for at least two seasons according to medical history
- •Sensitization to Bet v 1 (3.5 kU/L Bet v 1 specific IgE or higher as determined by UniCAP-FEIA)
- •CD203c or CD63 upregulation or histamine release upon challenge with Bet v 1 in basophil activation tests (at least 20% increase in upregulated CD63 or CD203c expression or histamine release on basophils upon stimulation compared to unstimulated controls measured by flow cytometry)
- •Willingness to comply with the study protocol and written informed consent
- •Subjects must have a standard health care insurance
- •Subjects must be available during the study period to complete all treatments and assessments
排除标准
- •History of anaphylaxis
- •Any severe chronic, malignant or general disease
- •Treatment with systemic or topical (intranasal, inhaled, external) corticosteroids within the previous 2 months before the start of the study
- •Treatment with antihistamines 3 days prior to the screening visit of the study
- •Treatment with other immunosuppressant drugs within the previous 6 months prior to the start of the study
- •Arterial hypertension or use of anti-hypertensive therapy, including beta-blockers
- •Contra-indications to skin prick testing such as: skin inflammation in the test area, urticaria facticia
- •Sensitisation to an allergen which is relevant during the birch pollen season (e.g., ash tree pollen, house dust mite etc)
- •Pregnant, lactating or sexually active women with childbearing potential who are not using a medically accepted birth control method
- •A mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study, and/or evidence of an uncooperative attitude
- •Participation in another clinical trial within one month prior to the study; however participation during the previous month solely in the form of blood donation and/or without other interventions will be accepted
- •Known alcohol or drug addiction or abuse
- •Risk of non-compliance with the study procedure
- •Active asthma currently necessitating treatment
- •Previous immunotherapy with birch pollen
- •Nasal polyps, history of chronic sinusitis or substantial deviation of the nasal septum
研究组 & 干预措施
Nasal Provocation with Birch Extract
Birch allergic patient receiving 3 consecutive nasal challenges with birch extract (Allergopharma). Total dose of 1.5ug of Bet v 1 per challenge
干预措施: Nasal Provocation with Birch Extract (Diagnostic Test)
Nasal Provocation with NaCl 0.9%
Birch allergic patient receiving 3 consecutive nasal challenges with sterile NaCl 0.9%. Total dose of 100ul per nostril per challenge
干预措施: Nasal Provocation with NaCl 0.9% (Other)
结局指标
主要结局
Allergen Specific IgE Rise
时间窗: 1 Year
To assess changes of allergen specific IgE levels after challenge with Birch pollen extract
次要结局
- IgE Levels in Nasal Secretions(1 Year)
- Total IgE Levels(1 Year)
- Assessing Immunoglobin Isotypes(1 Year)
- Changes in TH2 Cytokine patterns.(1 Year)
- IgE Production(1 Year)
- Subjective Symptom Assessment(1 Year)
- Nasal Blockage(1 Year)
- Skin Response(1 Year)
研究者
Ass.Prof.Dr.med. Josef Toth
Associate Professor, Doctor of Medicine
Medical University of Vienna