Effect of Symbicort on GR (Glucocorticoid Receptor) Translocation in Induced Sputum in Comparison With Budesonide, Formoterol and Placebo. A Single Dose Exploratory Study in Patients With Mild Asthma
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Changes in MKP-1 mRNA
研究概览
简要总结
To investigate a possible interaction between formoterol and budesonide on GR-translocation and to compare the effect of different doses of Symbicort (80/4.5 and 2x80/4.5 mcg) with the effect of budesonide (200 mcg and 800 mcg) on GR translocation, and to investigate the effect of the study drugs on exhaled NO (bronchial and alveolar fraction.
详细描述
Combination therapy with inhaled corticosteroids (ICS) and long-acting β(2)-adrenergic agonists (LABA) is reported to have superior effects on controlling asthma symptoms to ICS alone; however, there is no molecular-based evidence to explain the clinical effects. Here, the effect of the ICS/LABA combination was compared with ICS on glucocorticoid receptor (GR) activation in sputum macrophage.
In a randomised, double-blind cross-over placebo-controlled 6-visit study, 10 patients with mild asthma were given placebo, formoterol (Oxis(®) 12 μg), budesonide (Pulmicort(®) 200 μg :BUD200, or 800 μg :BUD800), or budesonide/formoterol combination (Symbicort(®)) as a single 100/6 μg (SYM100) or double 200/12 μg (SYM200) dose. Sputum macrophages were separated by plate adhesion from induced sputum. GR binding to the glucocorticoid-response elements on oligonucleotides (GR-GRE binding) was evaluated by ELISA. mRNA expression of MAP-kinase phosphatase (MKP)-1 and IL-8 were measured by quantitative RT-PCR.
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 (Participant, Investigator)
入排标准
- 年龄范围
- 21 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with mild steroid-naïve asthma (ATS criteria) of either sex with FEV1 >70 % pred
- •Able to produce sputum after sputum induction
- •Exhaled NO (flow 50 ml/s) ≥ 20 ppb
- •Written informed consent
排除标准
- •Current upper respiratory tract infections
- •Use of inhaled and/or oral GCS within 4 weeks prior to visit 1
- •Treatment with antileukotrienes, theophylline, tiotropium and ipratropium within 2 weeks prior to screening visit
- •Hypersensitivity to any of the investigational drugs or lactose
- •Use of any beta blocking agent (including eye-drops)
- •Women who are pregnant, breast-feeding or planning a pregnancy during the study. Women must be postmenopausal (at least one year must have passed after the last menstruation), surgically sterile or using acceptable contraceptives, as judged by the investigator
- •Any significant disease or disorder (e.g. cardiovascular, pulmonary (other than asthma), gastrointestinal, liver, renal, neurological, musculoskeletal, endocrine, metabolic, malignant, psychiatric, major physical impairment) which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, or may influence the results of the study, or the subjects ability to participate in the study
- •Inability to tolerate temporary withdrawal of bronchodilatory therapy
- •Subjects not considered capable, as judged by the investigator, of following instructions of the study, e.g. because of a history of alcohol or drug abuse or any other reason
- •Previous randomization in this study
研究组 & 干预措施
Placebo
placebo
干预措施: Placebos (Drug)
Formoterol
Oxis(®) 12 μg
干预措施: Formoterol Inhalant Powder (Drug)
Budesonide low dose
Pulmicort(®) 200 μg
干预措施: Budesonide Powder (Drug)
Budesonide high dose
Pulmicort(®) 800 μg
干预措施: Budesonide Powder (Drug)
Budesonide/formoterol combination single
single 100/6 μg SYM100
干预措施: Budesonide and Formoterol Product (Drug)
Budesonide/formoterol combination double
double 200/12 μg SYM200
干预措施: Budesonide and Formoterol Product (Drug)
结局指标
主要结局
Changes in MKP-1 mRNA
时间窗: 1-2h
Changes in MKP-1 mRNA measured by PCR
Changes in GR-GRE Binding
时间窗: 1-2h
The GR-GRE binding is the glucocorticoid receptor (GR) DNA binding affinity. GR-GRE activity as assed by enzyme-immunosorbent assay
IL8 mRNA
时间窗: 1-2h
Measured by PCR
次要结局
未报告次要终点