Anti-inflammatory Effects of Tiotropium in Patients With Stable COPD- A Multicenter Randomized Controlled Double-blind Study
试验速览
- 阶段
- 4 期
- 入组人数
- 50
- 试验地点
- 2
- 主要终点
- Change in concentration of TNF-alpha (mRNA level) in induced sputum
研究概览
简要总结
This study aims to assess the anti-inflammatory effects after 6 weeks treatment with tiotropium compared to placebo in patients with stable COPD
详细描述
Rationale: Acetylcholine is the primary parasympathetic neurotransmitter in the airways, and induces bronchoconstriction. Since the cholinergic tone appears to be the major reversible component of obstruction, muscarinic receptor antagonism and bronchodilation represent the primary goal of anticholinergic therapy in patients with chronic obstructive pulmonary disease (COPD). Long-acting anticholinergic therapy is central in GOLD stage B-D, because of improvements in lung function, quality of life, and especially reduction of exacerbations. The elicited reduction in exacerbations with the long-acting muscarinic antagonist (LAMA) tiotropium appears larger than that of the long-acting beta agonist (LABA) salmeterol even when the bronchodilation is similar. In asthma too, it has been shown that the addition of the tiotropium to inhaled corticosteroids (ICS)+LABA combination therapy reduces the number of severe exacerbations. These effects on exacerbation frequency suggest that tiotropium might exert anti-inflammatory effects in the airways next to bronchodilatory effects. There are multiple animal and in vivo studies to indeed suggest an anti-inflammatory effect of anticholinergics.
Such an anti-inflammatory effect of anticholinergic intervention could be clinically relevant; however it has not been previously demonstrated in patients with COPD.
The investigators hypothesize that tiotropium bromide reduces the ongoing inflammation in patients with COPD compared to placebo. The investigators expect a decrease of TNF-alpha mRNA in sputum after treatment with tiotropium bromide.
Objective: This research proposal aims to assess the anti-inflammatory effects after 6 weeks treatment with tiotropium compared to placebo in patients with stable COPD.
Study design: This will be a multicenter parallel design randomized controlled double-blinded study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double-blind
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
- •• Men or women, age >= 40 years.
- •A diagnosis of COPD according to the criteria of the GOLD organization
- •Post-bronchodilator FEV1 / FVC ratio < 70% (ERS equations) and post-bronchodilator FEV1 < 80%pred.
- •A smoking history of > 10 pack years.
- •post-bronchodilator FEV1 > 1.5 Litres and ability to produce sputum after hypertonic saline induction.
- •No upper or lower respiratory tract infection in the last 4 weeks necessitating antibiotic treatment or consisting of quite probable viral etiology.
- •Being in a stable phase of COPD, as judged by the investigator. No courses of systemic steroids or antibiotics for respiratory problems last 4 weeks
- •The participant needs to be able to understand the Dutch language
- •Signed and dated informed consent obtained before any study related procedures (including withdrawal of concomitant medication) are conducted.
排除标准
- •• Treatment with immune-modulating agents for any disease, including leuktriene receptor antagonists,
- •Treatment with long-acting anticholinergics <4 weeks before the start of the study.
- •Treatment with corticosteroids <4 weeks before the start of the study.
- •Targeted lung denervation therapy in the past.
- •Concomitant diagnosis of asthma.
- •Any significant other pulmonary disease or disorder (e.g. known alpha1-antitrypsine deficiency, significant bronchiectasis), as judged by the investigator.
- •Narrow angle glaucoma.
- •Azithromycine maintenance treatment.
- •Active malignant disease (at least 5 years malignant disease-free)
- •Other significant disease or disorder (like cardiovascular, gastrointestinal, liver, renal, neurological, musculoskeletal, endocrine, metabolic (including diagnosed diabetes), malignant, psychiatric, major physical impairment), which, in the opinion of the investigators may either put the patient at risk because of participation in the study, or may influence the results of the study, or the patient's ability to participate in the study.
- •Females of childbearing potential without an efficient contraception unless they meet the following definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH >40 mIU/mL or the use of one or more of the following acceptable methods of contraception:
- •Surgical sterilization (e.g. bilateral tubal ligation, hysterectomy).
- •Hormonal contraception (implantable, patch, oral, injectable).
- •Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/cream/suppository.
- •Continuous abstinence.
研究组 & 干预措施
Tiotropium respimat
Tiotropium respimat 2.5mcg two actuations once daily
干预措施: Tiotropium Bromide (Drug)
Placebo respimat
Placebo respimat two actuations once daily
干预措施: Tiotropium Bromide (Drug)
结局指标
主要结局
Change in concentration of TNF-alpha (mRNA level) in induced sputum
时间窗: 6 week treatment duration
To assess whether 6 weeks treatment with tiotropium elicts anti-inflammatory effects compared to placebo in patients with stable COPD, as measured by a change in TNF-alpha mRNA level in induced sputum
次要结局
- Change in concentration of sputum cell differentials in induced sputum(6 week treatment duration)
- Change in concentration cytokine protein level in blood serum(6 week treatment duration)
- Change in concentration of LTB4 level in induced sputum(6 week treatment duration)
- Change in concentration of cytokine protein level in induced sputum(6 week treatment duration)
- Change in concentration of cytokine mRNA level in induced sputum(6 week treatment duration)
- Change in health related quality of life (CCQ, CAT questionnaires)(6 week treatment duration)
- Change in concentration of cell differentials + CRP in blood serum(6 week treatment duration)
研究者
Huib A.M. Kerstjens
Full professor pulmonology; Head of department of Pulmonology and Tuberculosis; Principal Investigator
University Medical Center Groningen