Effect of Roflumilast on Airway Blood Flow as an Expression of Airway Inflammation in COPD
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 11
- 试验地点
- 1
- 主要终点
- Airway Blood Flow Reactivity (Delta Qaw)
研究概览
简要总结
The objectives of the proposed study are to determine 1) the effect of a single dose of Roflumilast on airway blood flow (Qaw) (study period 1) and 2) the effect of long-term Roflumilast treatment on airway blood flow reactivity delta Qaw)(study period 2) in patients with stable COPD who use ICS regularly.
详细描述
Participants will be enrolled in the study for three months There will be 6 study days (visits). The patients will be asked to come to the research laboratory in the morning of the study day. They will be instructed to abstain from ingesting alcoholic beverages or using PDE5 inhibitors the night before the study, and from consuming coffee or caffeinated drinks in the morning of the study day because of their potential acute cardiovascular actions. The patients will also be asked not to have a fatty breakfast on the study day to avoid potential effects of fat on the absorption of roflumilast.
The visits will be separated by at least 48 hours. Study period 1: The patients will be randomized into two arms: roflumilast or placebo. Qaw will be measured before and at 15, 30, 60, 120 and 240min in each arm (parallel design) Study period 2: Patients will be randomized to either roflumilast for 4 weeks or placebo for 4 weeks and airway blood flow reactivity will be measured at the end of the treatment period. The patients will then be taken off medication or placebo for 4 weeks and reassigned to the alternate treatment (roflumilast or placebo) for 4 weeks and airway blood flow reactivity will be measured after the this treatment period (cross-over design).
The treatments will be administered in a double-blind randomized design, using active roflumilast and identically appearing roflumilast placebo provided by Forest.
Visit 1
On this visit, a medical history will be obtained from the patients and they will undergo a physical examination and complete pulmonary function testing. If they meet entry criteria, Qaw will be measured before and 15 min after the inhalation of 180 µg albuterol using a spacer (ΔQaw). We have previously shown that vasodilation peaks between 5 and 30 min after inhaling this dose of albuterol in healthy non-smokers; in patients with COPD, who exhibit a vasodilatory response to inhaled albuterol, the peak effects also occur at the same time as in healthy subjects. Since all patients enrolled in the present study will be regular ICS users, we expect that all of them will have a vasodilator response to albuterol as previously shown.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 45 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Twenty-four patients with physician-diagnosed COPD (female and male, current smokers or ex-smokers) over the age of 45 years will be recruited for this study.
- •The patients will have to have a smoking history of at least 10 pack-years, and they must have been using an ICS regularly for at least 4 weeks at the time of screening.
- •Confirmation of the diagnosis of COPD will require the presence of persistent exertional dyspnea and a post-bronchodilator FEV1 of less than 80% of predicted and FEV1/FVC ratio less than 0.7 (GOLD stage ≥2). At entry into the study, the patients will have to be clinically stable; they will be allowed to remain on their regular COPD treatment regimen and use a LABA and/or LAMA until 24 hours before, and a SABA and/or short-acting muscarinic antagonist (SAMA) until 6 hours before coming to the laboratory. If using roflumilast, the subjects will have to discontinue it 4 weeks before entering into the study.-
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
- •Use of supplemental oxygen that cannot be discontinued during the laboratory visit
- •Subjects with known SABA or roflumilast intolerance
- •An acute COPD exacerbation within four weeks prior to the study
研究组 & 干预措施
SD placebo and MD roflumilast then MD placebo
Participants will receive placebo (single dose) followed by a 4 week treatment with 500ug roflumilast daily, followed by a 4 week washout period, followed by a 4 week treatment with placebo daily.
干预措施: Roflumilast Placebo (Drug)
SD placebo and MD roflumilast then MD placebo
Participants will receive placebo (single dose) followed by a 4 week treatment with 500ug roflumilast daily, followed by a 4 week washout period, followed by a 4 week treatment with placebo daily.
干预措施: Roflumilast (Drug)
SD placebo and MD placebo then MD roflumilast
Participants will receive placebo (single dose) followed by a 4 week treatment with placebo daily, followed by a 4 week washout period, followed by a 4 week treatment with 500ug roflumilast daily.
干预措施: Roflumilast Placebo (Drug)
SD placebo and MD placebo then MD roflumilast
Participants will receive placebo (single dose) followed by a 4 week treatment with placebo daily, followed by a 4 week washout period, followed by a 4 week treatment with 500ug roflumilast daily.
干预措施: Roflumilast (Drug)
SD roflumilast and MD placebo then MD roflumilast.
Participants will receive 500ug roflumilast (single dose) followed by a 4 week treatment with placebo daily, followed by a 4 week washout period, followed by a 4 week treatment with 500ug roflumilast daily.
干预措施: Roflumilast Placebo (Drug)
SD roflumilast and MD placebo then MD roflumilast.
Participants will receive 500ug roflumilast (single dose) followed by a 4 week treatment with placebo daily, followed by a 4 week washout period, followed by a 4 week treatment with 500ug roflumilast daily.
干预措施: Roflumilast (Drug)
SD roflumilast and MD roflumilast then MD placebo
Participants will receive 500ug roflumilast (single dose) followed by a 4 week treatment with 500ug roflumilast daily, followed by a 4 week washout period, followed by a 4 week treatment with placebo daily
干预措施: Roflumilast Placebo (Drug)
SD roflumilast and MD roflumilast then MD placebo
Participants will receive 500ug roflumilast (single dose) followed by a 4 week treatment with 500ug roflumilast daily, followed by a 4 week washout period, followed by a 4 week treatment with placebo daily
干预措施: Roflumilast (Drug)
结局指标
主要结局
Airway Blood Flow Reactivity (Delta Qaw)
时间窗: Immediate or 4 weeks
percentage of change on airway blood flow induced by albuterol.
次要结局
未报告次要终点
研究者
Adam Wanner
Professor of Medicine
University of Miami