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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00826566
Recruitment Status : Withdrawn (Suitable subjects could not be recruited within the estimated time frame.)
First Posted : January 22, 2009
Last Update Posted : September 23, 2015
Technologiestichting STW (NWO)
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Chronic Obstructive Pulmonary Disease Dietary Supplement: Caffeine Dietary Supplement: placebo Not Applicable

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Pilot Study to Investigate the Anti-inflammatory Effects of Caffeine in Subjects With Chronic Obstructive Pulmonary Disease (COPD)
Study Start Date : January 2009
Estimated Primary Completion Date : June 2009
Estimated Study Completion Date : September 2009

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: 1
500 mg caffeine capsules per day
Dietary Supplement: Caffeine
2 times 250 mg caffeine per day

Placebo Comparator: 2
500 mg placebo capsules
Dietary Supplement: placebo
2 times 250 mg per day

Primary Outcome Measures :
  1. Plasma concentrations of C-reactive protein (CRP) and the cytokines TNF-a, IL-6, IL-8 and IL-10. [ Time Frame: at the start and at the end of the intervention periods ]

Secondary Outcome Measures :
  1. Activation of poly-(ADP-ribose) polymerase (PARP)-1 activation and DNA repair in peripheral lymphocytes [ Time Frame: at the start and the end of the intervention periods ]
  2. Oxidative stress markers in plasma such as PGF2alpha [ Time Frame: at the start and the end of the intervention periods ]
  3. Plasma concentrations of caffeine and metabolites [ Time Frame: at the start and the end of the interventions ]
  4. Gene transcription levels of cytokines, redox enzymes and other proteins involved in inflammatory and oxidative stress response [ Time Frame: at the start and the end of the interventions ]
  5. Cytokine concentrations in whole blood after ex vivo stimulation with LPS [ Time Frame: at the start and the end of the interventions ]

Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00826566

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Maastricht University Medical Centre (UMC+)
Maastricht, Netherlands, 6200 MD
Sponsors and Collaborators
Maastricht University Medical Center
Technologiestichting STW (NWO)
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Principal Investigator: Geja J Hageman, PhD Dept. of Health Risk Analysis and Toxicology, UMC+, Maastricht, The Netherlands
Principal Investigator: Antje R Weseler, PhD Dept. of Pharmacology & Toxicology, UMC+, Maastricht, The Netherlands
Study Director: Aalt Bast, PhD, Prof. Dept. of Pharmacology & Toxicology, UMC+, Maastricht, The Netherlands
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Responsible Party: Maastricht University Medical Center Identifier: NCT00826566    
Other Study ID Numbers: STW6041
First Posted: January 22, 2009    Key Record Dates
Last Update Posted: September 23, 2015
Last Verified: September 2009
Keywords provided by Maastricht University Medical Center:
chronic systemic inflammation
oxidative stress
stable COPD GOLD stage II with CRP levels ≥ 3 mg/l
Additional relevant MeSH terms:
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Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases
Central Nervous System Stimulants
Physiological Effects of Drugs
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Purinergic P1 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents