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

Not Applicable

Withdrawn

• Conditions: Chronic Obstructive Pulmonary Disease
• Interventions: Dietary Supplement: Caffeine; Dietary Supplement: placebo

• Registration Number: NCT00826566
• Lead Sponsor: Maastricht University Medical Center

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2009-01
• Study First Submitted: 2009-01-21
• Study First Submitted QC: 2009-01-21
• Study First Posted: 2009-01-22
• Primary Completion: 2009-06
• Status Verified: 2009-09
• Study Completion: 2009-09
• Last Update Submitted: 2015-09-22
• Last Update Posted: 2015-09-23

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: Male
• Target Recruitment: Not specified

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
1	Caffeine	500 mg caffeine capsules per day
2	placebo	500 mg placebo capsules

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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
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

Trial Locations

Locations (1)

Maastricht University Medical Centre (UMC+); 🇳🇱 Maastricht, Netherlands