Effect of COX-2 Inhibition on Allergen-induced Airway Obstruction in Subjects With Asthma
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Allergen PD20 FEV1
研究概览
简要总结
The study is part of a research programme into mechanisms of asthmatic airway obstruction, focusing on the role of lipid mediators such as the prostaglandins.
To this end the effect of a non-steroidal anti-inflammatory drug, the selective COX-2 inhibitor etoricoxib, will be evaluated in the allergen challenge setting in twelve subjects with intermittent allergic asthma. Active treatment for 10 to 13 days will be compared with an identical study period with no treatment in a cross-over, randomised design. Rising dose allergen challenges will be performed on three occasions to assess possible changes in airways responsiveness. Sampling of blood, urine, saliva and sputum will be done to allow for analyses of the production of prostaglandins and other lipid mediators, of the efficacy of COX-2 inhibition as well as of regulation of immune cells.
It is hypothesized that inhibition of COX-2 by virtue of inhibition of bronchoprotective prostaglandin E2 leads to a slightly exaggerated airway response to allergen exposure.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Double (Investigator, Outcomes Assessor)
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
- •Female or male aged 18 to 55 years inclusive
- •A history of asthma for at least 6 months with at least one of the following:
- •response to standard asthma treatment
- •episodic wheezing
- •change in lung function over short periods of time
- •A positive methacholine challenge test as evidenced by a PD20 ≤7256 µg cumulated dose within 8 weeks prior to screening or at the screening visit.
- •Stable intermittent asthma, only using bronchodilator therapy as needed for the last 4 weeks.
- •FEV1 ≥ 75% of predicted.
- •A positive skin prick test to pollen (grass, birch, mugwort) or animal dander (dog, cat)
排除标准
- •Known or suspected hypersensitivity to coxibs
- •Any significant respiratory disease other than asthma
- •Respiratory tract infection within 4 weeks before inclusion.
- •Any significant disease or disorder which, in the opinion of the investigator, may put the patient at risk because of participation in the study. In particular previous or present history of cardiovascular disease, ie myocardial infarction, stroke, severe hypertension, left ventricular heart failure and/or pulmonary hypertension are strict exclusion criteria.
- •Current or former smoker within the last year and a smoking history of >4 packyears
- •Pregnancy/breastfeeding
- •inhaled glucocorticosteroid treatment or use of oral corticosteroids for the last 8 weeks prior to inclusion or during the study.
- •inhaled long-acting or oral beta2-agonists, anticholinergic bronchodilators, cromones, antihistamines, theophyllines and antileukotrienes within 2 weeks of screening or during the study.
- •paracetamol, NSAIDs or any other antiinflammatory drugs the last 2 weeks prior to inclusion or during the study.
- •need of any other regular drug treatment that may interfere with the study outcomes.
- •BMI >30 kg/m
- •Use of any beta-blocking agent
- •Any non-asthma-related, clinically significant abnormal finding in physical and/or vital signs, and/or in hematology or blood chemistry tests at visit 1, which in the opinion of the investigator, may put the patient at risk because of participation in the study.
研究组 & 干预措施
Etoricoxib
10-13 days treatment with etoricoxib
干预措施: Etoricoxib (Drug)
结局指标
主要结局
Allergen PD20 FEV1
时间窗: 10 to 13 days
次要结局
- Urinary prostaglandin E2 and D2 concentrations(10-13 days)
研究者
Barbro Dahlen
MD PhD
Karolinska University Hospital