Effect of an Inhaled Glucocorticoid-long-acting Beta Adrenergic Agonist on Endothelial Function in COPD
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- long term effect of a glucocorticoid/long-acting beta-agonist on endothelial function in the bronchial artery.
研究概览
简要总结
In the present study, the investigators wish to address the effect of a glucocorticoid/long-acting beta-agonist preparation on endothelial function in COPD patients who do not currently smoke (ex-smokers) by measuring endothelium-dependent (albuterol response) and endothelium-independent (NTG response) vasodilation in the bronchial artery, reflecting endothelium-dependent and endothelium-independent vasodilation (drug-induced increase in Qaw, ΔQaw). With this approach the investigators will test the hypothesis that in stable ICS-naïve COPD patients, endothelium-dependent vasodilation is restored with a glucocorticoid/long-acting beta-agonist preparation, presumably resulting from the glucocorticoid component.
详细描述
To test the premise and to characterize the time dependence of the responses, the investigators propose the following two aims:
- To determine the effect of a medium dose glucocorticoid/long-acting beta-agonist preparation (250 μg fluticasone plus 50 μg salmeterol) administered for 3 weeks on inhaled albuterol and sub-lingual NTG induced vasodilation in the bronchial artery, as assessed by ΔQaw in stable glucocorticoid-naïve COPD patients, and to re-assess the responses after a 3 week glucocorticoid/long-acting beta-agonist washout period.
- To determine inhaled albuterol and sub-lingual NTG-induced vasodilation (ΔQaw) before, and 30 min and 120 min after a single medium dose of an ICS (220 μg fluticasone) in stable glucocorticoid- naïve COPD patients.
For both aims, the protocol design will be placebo-controlled and double-blind. For the second aim, only fluticasone pretreatment will be possible because the salmeterol component of the fluticasone/salmeterol combination preparation could influence albuterol responsiveness irrespective of any glucocorticoid effect. The timing of the endothelial function measurements in the long-term glucocorticoid/long-acting beta-agonist protocol and single dose ICS protocol is based on the past experience with ICS on airway vascular function. Single dose effects were seen within 15-30 min and waned by 90 min (25,26), while long-term treatment effects were no longer seen 3 weeks after ICS withdrawal (16).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 盲法
- Double (Participant, Investigator)
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
- 否
入选标准
- •Smoking history of at least 10 pack-years and to have quit smoking at least 1 year before the study. -Diagnosis of COPD
- •Post-bronchodilator FEV1 of less than 75% of predicted and FEV1/FVC ratio less than 0.7 (GOLD stage ≥2).
- •At entry into the study, the subjects will have to be clinically stable; they will be allowed to use short-acting and long-acting β2 - adrenergic agonists and cholinergic antagonists as their usual airway medication.
排除标准
- •Women of childbearing potential who do not use accepted birth control measures; pregnant and breast feeding women.
- •Use of cardiovascular medications that cannot be held on the study days
- •Use of oral airway medications or anti-inflammatory agents
- •Subjects with known beta-adrenergic agonist or NTG intolerance
- •Acute respiratory infection within four weeks prior to the study
- •A body mass index > 30
研究组 & 干预措施
Matching Placebo
Participants will be treated with placebo twice a day for 3 weeks.
干预措施: Placebo (Drug)
Matching Placebo
Participants will be treated with placebo twice a day for 3 weeks.
干预措施: Fluticasone /salmeterol (Drug)
Fluticasone/salmeterol
Participants will be assigned to inhaled fluticasone/salmeterol twice a day for 3 weeks.
干预措施: Fluticasone /salmeterol (Drug)
结局指标
主要结局
long term effect of a glucocorticoid/long-acting beta-agonist on endothelial function in the bronchial artery.
时间窗: 3 weeks
To determine the effect of a medium dose glucocorticoid/long-acting beta-agonist preparation (250 μg fluticasone plus 50 μg salmeterol) or placebo administered for 3 weeks on inhaled albuterol and sub-lingual NTG induced vasodilation in the bronchial artery, as assessed by ΔQaw in stable glucocorticoid-naïve COPD patients, and to re-assess the responses after a 3 week washout period.
次要结局
- acute effect of an ICS on bronchial endothelial function in stable glucocorticoid-naïve COPD patient.(30 minutes and 120 minutes after inhaled albuterol and sub-lingual NTG)
研究者
Adam Wanner
Professor of Medicine
University of Miami