Anti-inflammatory Effects of Caffeine in Chronic Obstructive Pulmonary Disease (COPD) Subjects

Study Overview
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Brief Summary
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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.

Official Title
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Pilot Study to Investigate the Anti-inflammatory Effects of Caffeine in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Dietary Supplement: Caffeine
* Dietary Supplement: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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).

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>500 mg caffeine capsules per day | Dietary Supplement: Caffeine<br>* 2 times 250 mg caffeine per day<br>|
| Placebo Comparator: 2<br>500 mg placebo capsules | Dietary Supplement: placebo<br>* 2 times 250 mg per day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentrations of C-reactive protein (CRP) and the cytokines TNF-a, IL-6, IL-8 and IL-10. |  | at the start and at the end of the intervention periods | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, caffeine, chronic systemic inflammation, oxidative stress, supplementation, stable COPD GOLD stage II with CRP levels ≥ 3 mg/l