The Effect of Montelukast Therapy on mRNA Profile of Matrix Metalloproteinases and Their Inhibitors in the Sputum of Patients With Asthma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Primary endpoint is the MMP and TIMP mRNA profile relative to a housekeeping gene
研究概览
简要总结
Matrix metalloproteinases (MMPs) are a group of 24 zinc containing enzymes in man. These enzymes were originally described as cleaving extracellular matrix (ECM) substrates with a predominant role in ECM homeostasis, but it is now clear that they have much wider functionality. An imbalance between MMP activity and that of their inhibitors (tissue inhibitors of metalloproteinases, TIMPs) is considered to play a critical role in the synthesis or degradation of the extracellular matrix of the airway architecture which results in fixed airflow obstruction in both asthma and chronic obstructive pulmonary disease (COPD). Using quantitative real time polymerase chain reaction (RT-PCR) the investigators have identified a difference between the level of steady state mRNA for MMP-9, MMP-14 and MMP-2 in 2 patients with asthma compared to 4 healthy controls using our method. However the investigators require further refinement of the process in order to optimise RNA quality and to evaluate the effect of montelukast across the entire family of MMPs and their inhibitors (TIMPs).
详细描述
The following measurements will be performed at screening:
- Informed consent
- Clinical examination
- Spirometry
- Induced sputum
The following will be performed after 8 weeks of study medication:
- Clinical examination
- Spirometry
- Induced sputum
- Diary Card
Spirometry:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, aged 18 to 60 years.
- •Diagnosed with asthma, defined as episodic chest tightness, wheezing and dyspnoea, cough.
- •Non-Smoker or Ex-Smoker for at least 10 years and a smoking history of less than 5 pack years.
- •History of asthma symptoms for more than 10years.
- •Receiving as required short acting bronchodilators.
- •Post bronchodilator FEV1 50 to 100 % predicted
- •Evidence of airway calibre reversibility within the previous 12 months: reversibility to salbutamol of 12% following 400mcg inhaled salbutamol, histamine PC20 < 8mg/ml, diurnal variation in peak expiratory flow of 20%.
- •Able to produce sputum after induction with saline.
- •Exclusion criteria:
- •Cardiac or pulmonary disease other than asthma.
- •Respiratory infection defined as fever, nasal/sinus congestion, fatigue, cough, antibiotic use or yellow/green sputum within 4 weeks prior to study.
- •Receiving inhaled or oral corticosteroid therapy, long acting Beta2 agonist therapy or leukotriene modifying therapy for the previous 1 month.
- •Severe or uncontrolled co-morbid disease.
- •Pregnancy or breastfeeding.
- •Unable to give written informed consent
排除标准
- 未提供
研究组 & 干预措施
montelukast group
Identified patients with asthma to recieve Montelukast 10 mg (Merck Sharp & Dohme Ltd, Herts, UK) at 0800 am once daily for 8 weeks.
干预措施: montelukast (Drug)
结局指标
主要结局
Primary endpoint is the MMP and TIMP mRNA profile relative to a housekeeping gene
时间窗: 8 weeks
次要结局
- The difference between treatment with montelukast for 8 weeks and placebo for mRNA for MMP and TIMP(8 weeks)
- The difference between treatment with montelukast for 8 weeks and placebo for Spirometry - FEV1, FVC, FEV1/FVC ratio(8 weeks)
- The difference between treatment with montelukast for 8 weeks and placebo for Induced sputum differential cell count(8 weeks)