A Double-blind, Placebo-controlled, Crossover Study to Evaluate the Effects of Tiotropium Bromide on Gas Exchange in Subjects With COPD During Exercise
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 20
- 主要终点
- Efficiency of gas exchange Ve/VO2 and Ve/VCO2 before and after 3 weeks treatment with tiotropium compared to placebo.
研究概览
简要总结
The purpose of this study is to determine the effect of treatment with tiotropium bromide on efficiency of gas exchange and exercise performance in COPD subjects during exercise.
详细描述
This study will investigate the effect of tiotropium on gas exchange during exercise. In addition, we hypothesize that bronchodilation by tiotropium will open functional lung units improving gas exchange in subjects with COPD. While other studies have shown that tiotropium improves exertional dyspnea and exercise tolerance, and reduces resistive and elastic work in subjects with COPD, there have been no investigations of the effects of anti-cholinergic bronchodilation on gas exchange. This study will confirm and extend earlier observations on exertional dyspnea and exercise tolerance.
Efficiency of gas exchange will be evaluated through assessments of metabolic demand (VO2) cardiac output (Q), ventilation (V) in overall terms i.e. Q/VO2, V/VO2.
Improved efficiency of gas exchange will reduce the ventilatory demand for a given workload, providing an alternate mechanism for the observed improvement in exertional dyspnea and exercise tolerance in subjects with COPD. The overall ventilation required to meet metabolic demands is dependent on the alveolar volume which can be easily measured using inert gases. This is conveniently measured during the DLco maneuver which will be measured. In general, ventilation increases with metabolic demand but increases progressively as the VA and KCO decline in patients with COPD. These factors may be amenable to improvement using anticholinergic agents. In addition the recruitment of additional alveolar volume provides an additional pathway for blood flow through the lung increasing overall cardiac output and enhancing the responsiveness of peripheral muscle in these patients. These have not been considered and exploited as potential therapeutic goals.
Study Evaluations:
Treatment Period: Visits 2, 3, 5 and 6
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must be current or ex-smokers with a cigarette smoking history of > 10 pack years.
- •All patients must have a diagnosis of COPD.
- •Patients maintained on a daily dose of inhaled corticosteroids need to be at a constant dose at 4 weeks prior to study entry.
排除标准
- •Patients with significant diseases other than COPD.
- •Patients with a history of a recent (i.e. six months or less) myocardial infarction.
- •Patients with unstable or life threatening cardiac arrhythmias including any patient with a newly diagnosed, clinically relevant arrhythmia on the ECG performed on Visit
- •Patients who have been hospitalized for heart failure (NYHA class III or IV) within the past year.
- •Patients with a history of life threatening pulmonary obstruction, or history of cystic fibrosis or clinically evident bronchiectasis.
- •Patients who have undergone thoracotomy with pulmonary resection.
- •Patients with any respiratory infection or exacerbation in the six weeks prior to Visit
- •Patients who regularly use daytime oxygen therapy for more than one hour per day and who in the investigator's opinion, will be unable to abstain from the use of oxygen therapy during testing.
- •Patients who are currently in a pulmonary rehabilitation program or who have completed a pulmonary rehabilitation program within four weeks of Visit
- •Patients with known active tuberculosis.
- •Patients with a history of cancer within the past five years.
- •Pregnant or breastfeeding women or women of childbearing potential not using a medically approved means of contraception.
- •Patients with known hypersensitivity to anti-cholinergic drugs, lactose or any other components of the inhalation capsule delivery system.
- •Patients with a history of significant alcohol or drug abuse in the previous year.
- •Patients with have taken an investigational drug within 30 days or 6 half lives (whichever is greater) prior to Visit
- •Patients using oral corticosteroid medication and unstable doses (i.e. less than six weeks on a stable dose) or at doses in excess of the equivalent of 10 mg prednisone per day or 20 mg every other day.
- •Patients who use rescue medication (Salbutamol) more than 8 puffs/day.
- •Patients who have used tiotropium (Spiriva) within 4 weeks prior to Visit
- •Patients who have frequent exacerbations which could be expected to interfere with participation in the trial.
研究组 & 干预措施
1
Tiotropium
干预措施: tiotropium bromide (Drug)
2
Placebo
干预措施: Placebo (Other)
结局指标
主要结局
Efficiency of gas exchange Ve/VO2 and Ve/VCO2 before and after 3 weeks treatment with tiotropium compared to placebo.
时间窗: Before and after 3 weeks treatment with tiotropium compared to placebo.
次要结局
- Intensity of dyspnea(Before and after 3 weeks treatment with tiotropium compared to placebo.)
- Effort during incremental and steady state exercise(Before and after 3 weeks treatment with tiotropium compared to placebo.)
- Exercise endurance capacity(Before and after 3 weeks treatment with tiotropium compared to placebo.)
- Dyspnea and leg effort(Before and after 3 weeks treatment with tiotropium compared to placebo.)
- Ventilatory capacity(Before and after 3 weeks treatment with tiotropium compared to placebo.)
- Alveolar volume(Before and after 3 weeks treatment with tiotropium compared to placebo.)
- Kco(Before and after 3 weeks treatment with tiotropium compared to placebo.)
- Cardiac output at rest and during steady state exercise before and after 3 weeks treatment with tiotropium compared to placebo.(Before and after 3 weeks treatment with tiotropium compared to placebo.)
- Ventilation/perfusion before and after 3 weeks treatment with tiotropium compared to placebo(Before and after 3 weeks treatment with tiotropium compared to placebo.)
- Ventilation during incremental and steady state exercise before and after 3 weeks treatment with tiotropium compared to placebo.(Before and after 3 weeks treatment with tiotropium compared to placebo.)