Clinical trial NCT00826566: Anti-inflammatory Effects of Caffeine in Chronic Obstructive Pulmonary Disease (COPD) Subjects
Official title: Pilot Study to Investigate the Anti-inflammatory Effects of Caffeine in Subjects With Chronic Obstructive Pulmonary Disease (COPD)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: COPD
caffeine
chronic systemic inflammation
oxidative stress
supplementation
stable COPD GOLD stage II with CRP levels ≥ 3 mg/l
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
Collaborators: name: Technologiestichting STW (NWO)
First posted: 2009-01-22
Enrollment: 0
Sex: MALE
Minimum age (years): 40
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

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.


Eligibility criteria: 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).

Primary outcomes:
measure: Plasma concentrations of C-reactive protein (CRP) and the cytokines TNF-a, IL-6, IL-8 and IL-10.
timeFrame: at the start and at the end of the intervention periods
Secondary outcomes:
measure: Activation of poly-(ADP-ribose) polymerase (PARP)-1 activation and DNA repair in peripheral lymphocytes
timeFrame: at the start and the end of the intervention periods
measure: Oxidative stress markers in plasma such as PGF2alpha
timeFrame: at the start and the end of the intervention periods
measure: Plasma concentrations of caffeine and metabolites
timeFrame: at the start and the end of the interventions
measure: Gene transcription levels of cytokines, redox enzymes and other proteins involved in inflammatory and oxidative stress response
timeFrame: at the start and the end of the interventions
measure: Cytokine concentrations in whole blood after ex vivo stimulation with LPS
timeFrame: at the start and the end of the interventions
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Centre (UMC+)
Study officials:
affiliation: Dept. of Health Risk Analysis and Toxicology, UMC+, Maastricht, The Netherlands
name: Geja J Hageman, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dept. of Pharmacology & Toxicology, UMC+, Maastricht, The Netherlands
name: Antje R Weseler, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dept. of Pharmacology & Toxicology, UMC+, Maastricht, The Netherlands
name: Aalt Bast, PhD, Prof.
role: STUDY_DIRECTOR
References: