Nasal Allergen Challenge: Standardisation for House Dust Mite and Silver Birch Allergen Extracts
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- Total nasal symptom score, area under the curve, during nasal allergen challenge
研究概览
简要总结
This study aims to establish dose-responses to nasal allergen challenge using silver birch pollen and house dust mite allergen extracts in participants with allergic rhinitis, sensitised to either or both of these allergens. The allergen extracts used will be Itulazax tablets (silver birch pollen allergen sublingual tablets, ALK-Abello, Denmark) and Acarizax tablets (house dust mite allergen sublingual tablets, ALK-Abello, Denmark). The results will allow identification of the dose of each allergen typically producing a moderate severity response, which could then be used in future, interventional and investigational studies.
A control group - healthy individuals with no allergic rhinitis - will be recruited to demonstrate the absence of an irritant/non-allergic effect of the nasal allergen challenge procedure.
详细描述
Nasal allergen challenge (NAC) is a useful tool in the investigation of allergic rhinitis, including grass pollen-induced seasonal allergic rhinitis (hay fever). The investigators have experience in using NAC to investigate the clinical and immunological effects of allergen exposure and in using NAC as a surrogate outcome to assess the efficacy of treatments for allergic rhinitis. The procedure is safe and well tolerated.
For NAC to be a valid tool, it is essential that the allergen extracts used are standardised in terms of concentration and stability in solution. The investigators recently undertook a study comparing the effects of two different grass pollen allergen extracts when used for NAC. The investigators found that the use of a lyophilizate pollen tablet, designed for sublingual immunotherapy treatment, was a suitable alternative to using dissolved dry powder allergen, designed for subcutaneous immunotherapy treatment. The study was necessary because the dry powder product was being phased out by the manufacturer.
The investigators now intend to undertake a similar study using lyophilizate tablets for two further common environmental allergens, house dust mite and silver birch tree pollen. The products used will be as follows: Acarizax® House Dust Mite lyophilizate tablet and Itulazax® Silver Birch Pollen lyophilizate tablet, both manufactured by ALK-Abello, Denmark.
House dust mite (HDM) is the most common indoor allergen trigger in individuals with allergic rhinitis and allergic asthma in the UK; silver birch (SB) pollen is a common cause of springtime hay fever. This will allow us to determine the suitability of using lyophilizate tablets as an allergen source for NAC for these two allergens in future interventional studies.
In this study, the investigators will recruit 20 volunteers with house dust mite induced allergic rhinitis (+/- controlled asthma) and 20 volunteers with silver birch pollen induced allergic rhinitis (+/- controlled asthma); individuals allergic to both allergens will be eligible for both parts of the study. HDM allergic volunteers will undergo a graded, up-dosing NAC with HDM allergen tablet extract; SB allergic volunteers will undergo a graded, up-dosing NAC with SB allergen tablet extract; dual allergic individuals will be given the option of undergoing challenges to both allergens, at least 4 weeks apart.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Inclusion criteria (HDM allergic volunteers):
- •Adults aged 18 to 65 years
- •A clinical history of perennial allergic rhinitis for at least 2 years with house dust mite allergen a potential cause of symptoms
- •Positive skin prick test response, defined as wheal diameter ≥ 5 mm, to house dust mite allergen extract
- •For women of childbearing age, a negative urine pregnancy test at the time of screening and willingness to use an effective form of contraception for the duration of involvement in the study.
- •The ability to give informed consent and comply with study procedures.
- •Inclusion criteria (SB allergic volunteers):
- •Adults aged 18 to 65 years.
- •A clinical history of seasonal allergic rhinitis in February-May for at least 2 years.
- •Positive skin prick test response, defined as wheal diameter ≥ 5 mm, to silver birch pollen allergen extract.
- •For women of childbearing age, a negative urine pregnancy test at the time of screening and willingness to use an effective form of contraception for the duration of involvement in the study.
- •The ability to give informed consent and comply with study procedures.
- •Inclusion criteria for non-atopic controls
- •Adults aged 18 to 65 years.
- •The ability to give informed consent and comply with study procedures.
排除标准
- •Exclusion criteria (allergic volunteers):
- •History of previous allergen immunotherapy to the relevant allergen being tested in the past 10 years
- •Pre-bronchodilator FEV1 < 70% of predicted value at screening.
- •Perennial asthma requiring regular inhaled corticosteroids.
- •History of emergency visit or hospital admission for asthma in the previous 12 months.
- •History of chronic obstructive pulmonary disease
- •History of significant recurrent acute sinusitis, defined as 2 episodes per year for the last 2 years, all of which required antibiotic treatment.
- •History of chronic sinusitis, defined as sinus symptoms lasting greater than 12 weeks that includes 2 or more major factors or 1 major factor and 2 minor factors. Major factors are defined as facial pain or pressure, nasal obstruction or blockage, nasal discharge or purulence or discolored postnasal discharge, purulence in nasal cavity, or impaired or loss of smell. Minor factors are defined as headache, fever, halitosis, fatigue, dental pain, cough, ear pain, pressure, or fullness.
- •At screening visit, current symptoms of, or treatment for, upper respiratory tract infection, acute sinusitis, acute otitis media, or other relevant infectious process; serous otitis media is not an exclusion criterion. Participants may be re-evaluated for eligibility after symptoms resolve.
- •History of life-threatening anaphylaxis or angioedema.
- •Ongoing systemic immunosuppressive treatment.
- •The use of any investigational drug within 30 days of the screening visit.
- •The presence of any medical condition that the investigator deems incompatible with participation in the study.
- •Exclusion criteria for non-atopic controls
- •A history of hay fever, chronic rhinitis/rhinosinusitis other than symptoms experienced during viral colds or other respiratory tract infections.
- •A positive skin prick test to any of a panel of common aeroallergens including grass pollen (Timothy grass), silver birch (Betula verrucosa), house dust mite (Dermatophagoides pteronyssinus), cat hair (Felis domesticus), dog hair (Canis familiaris), and common moulds (Aspergillus fumigatus., Cladosporium sp., Alternaria sp.), with adequate positive and negative controls.
- •Pre-bronchodilator FEV1 < 70% of predicted value at screening.
- •Perennial asthma requiring regular inhaled corticosteroids.
- •History of emergency visit or hospital admission for asthma in the previous 12 months.
- •History of chronic obstructive pulmonary disease
- •At screening visit, current symptoms of, or treatment for, upper respiratory tract infection, acute sinusitis, acute otitis media, or other relevant infectious process; serous otitis media is not an exclusion criterion. Participants may be re-evaluated for eligibility after symptoms resolve.
- •History of life-threatening anaphylaxis or angioedema.
- •Ongoing systemic immunosuppressive treatment.
- •The use of any investigational drug within 30 days of the screening visit.
- •The presence of any medical condition that the investigator deems incompatible with participation in the study.
结局指标
主要结局
Total nasal symptom score, area under the curve, during nasal allergen challenge
时间窗: 0-90 minutes
0-12 scale
次要结局
- Peak nasal inspiratory flow, area under the curve, during nasal allergen challenge(0-90 minutes)