Pilot Study to Investigate the Anti-inflammatory Effects of Caffeine in Subjects With Chronic Obstructive Pulmonary Disease (COPD)
试验速览
- 阶段
- 不适用
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Plasma concentrations of C-reactive protein (CRP) and the cytokines TNF-a, IL-6, IL-8 and IL-10.
研究概览
简要总结
Nowadays it has become evident that a chronic systemic inflammation is present in patients suffering from chronic obstructive pulmonary disease (COPD).
The role of the nuclear enzyme poly(adenosine diphosphate-ribose)polymerase (PARP) as a key mediator within these systemic inflammatory processes as well as in COPD associated exercise intolerance and muscle weakness could recently been identified. The attenuating effect of dietary ingredients with PARP inhibiting activity on systemic inflammation was supported by data from in vitro and in vivo studies, from other groups as well as from our own lab. We identified several caffeine metabolites as potent inhibitors of the most abundant PARP-isoform PARP-1 in-vitro, in animal models as well as in ex-vivo experiments with whole blood from COPD patients.
However, clinical data with respect to their anti-inflammatory effects in COPD patients are currently not available for none of these substances. Therefore, the current clinical pilot study is intended to establish for the first time clinical data (proof of principle) on the anti-inflammatory potential of caffeine metabolites.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 70 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •COPD GOLD stage II (50% ≤ FEV1< 80%)
- •CRP plasma levels ≥ 3 mg/l
- •BMI > 20 kg/m2 and < 30 kg/m2
- •Diastolic blood pressure (DBP)=60-90 mmHg, Systolic blood pressure (SBP)=100 150 mmHg
排除标准
- •Physical and/or mental disease or major surgery in the present or the past that might limit participation in or completion of the study
- •Reported current or previous metabolic (e.g. diabetes), cardiovascular and/or renal diseases
- •Known presence of a carcinoma
- •Acute and/or chronic inflammatory condition such as arthritis, arthrosis, chronic colitis, etc. during three months before entry of the study
- •Respiratory tract infection or exacerbation of COPD for at least 8 weeks prior to the start of the study
- •Change in treatment regime of the COPD subjects for at least 8 weeks prior to the start of the study
- •Use of laxatives, anti-diarrhoeal drugs and any other medication that can influence the uptake of the investigational products and/or influence their metabolism during the trial
- •During the month prior to the start of the study and during the study the use of antibiotics and/or local and systemic steroidal (glucocorticoids) and non-steroidal anti-inflammatory drugs (NSAID)
- •Abnormal constant dietary eating habits and a coffee consumption of less than 3 cups per day (i.e. a usual daily intake of <400 mg caffeine).
研究组 & 干预措施
2
500 mg placebo capsules
干预措施: placebo (Dietary Supplement)
1
500 mg caffeine capsules per day
干预措施: Caffeine (Dietary Supplement)
结局指标
主要结局
Plasma concentrations of C-reactive protein (CRP) and the cytokines TNF-a, IL-6, IL-8 and IL-10.
时间窗: at the start and at the end of the intervention periods
次要结局
- Activation of poly-(ADP-ribose) polymerase (PARP)-1 activation and DNA repair in peripheral lymphocytes(at the start and the end of the intervention periods)
- Oxidative stress markers in plasma such as PGF2alpha(at the start and the end of the intervention periods)
- Plasma concentrations of caffeine and metabolites(at the start and the end of the interventions)
- Gene transcription levels of cytokines, redox enzymes and other proteins involved in inflammatory and oxidative stress response(at the start and the end of the interventions)
- Cytokine concentrations in whole blood after ex vivo stimulation with LPS(at the start and the end of the interventions)