Double Blind, Randomized, Placebo-controlled, Two-way Crossover, Pilot Study to Assess the Effect of High Dose N-acetylcysteine on Small Airways and on Inflammation and Oxidative Stress in COPD Patients.
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- To assess the effect of high dose NAC (1800 mg)on small airways by measuring the total and peripheral airway resistance calculated with CFD
研究概览
简要总结
Studies suggest that N-acetylcysteine (NAC) potentially reduces inflammation and hyperinflation in patients with COPD.
In this pilot study the efficacy, safety and tolerability of high dose NAC in 12 patients with moderate COPD will be examined. These patients will receive a placebo for 12 weeks and NAC for 12 weeks in a dosage of 3 times 600 mg a day on top of their usual medication in a randomized crossover design. All subjects will be followed for 28 weeks.
The effect of high dose NAC on small airways will be assessed by measuring the total and peripheral airway resistance calculated with Computational Fluid Dynamics (CFD). The effect on oxidative stress will be assessed by measuring exhaled NO and specific markers (CRP, erythrocyte sedimentation rate, IL-6, 8-isoprostane, H2O2, TNF-alfa, glutathione, GPX, SOD and IL-8) in blood and Exhaled Breath Condensate (EBC). Dynamic and static lung volumes will be assessed by spirometry, body plethysmography and diffusion. Quality of life and symptoms will be assessed by the St George Respiratory Questionnaire.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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 with documented COPD based on the following criteria:
- •Smoking history of at least 10 pack-years
- •Decreased Tiffeneau index (FEV1/(FVC < 0.70)
- •Patients aged ≥ 40 years
- •Patients who stopped smoking since more than 1 month
- •Patients who present moderate COPD with an FEV1 between 50 and 80% of predicted (GOLD 2)
- •Patients should be treated according to GOLD guidelines
排除标准
- •Unstable patients who developed an exacerbation during the last 8 weeks
- •Patients who are current smokers or stopped less than 1 month
- •Patients who are allergic to acetylcysteine or to another element of the product
- •Patients with phenylketonuria or an untreated active peptic ulcer
- •Patients with any stage kidney and/or heart insufficiency or hypertension
- •Patients already treated with NAC for more than 6 months or during the last 3 months
- •Patients on continuous treatment with oral, inhalation, intravenous or intramuscular corticosteroids
- •Patients who are pregnant or are breast-feeding
- •Patients who are treated with orally administered cephalosporins
- •Patients using supplements containing antioxidants as vitamins C or E
研究组 & 干预措施
1
干预措施: N-acetylcysteine (Drug)
2
干预措施: placebo (Drug)
结局指标
主要结局
To assess the effect of high dose NAC (1800 mg)on small airways by measuring the total and peripheral airway resistance calculated with CFD
时间窗: at baseline, after 12 weeks of placebo and after 12 weeks of NAC
To assess the effect of high dose NAC (1800 mg)on oxidative stress by measuring exhaled NO and oxidative stress markers in blood and EBC
时间窗: at baseline, after 12 weeks of placebo and after 12 weeks of NAC.
次要结局
- To assess the tolerability and safety of high dose NAC(all visits)
- To assess dynamic and static lung volumes by spirometry, body plethysmography and diffusion(will be assessed at all visits)
- To assess quality of life by the SGRQ(will be assessed at all visits)
研究者
Wilfried De Backer
MD PhD
University Hospital, Antwerp