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

This study has been withdrawn prior to enrollment.
(Suitable subjects could not be recruited within the estimated time frame and via the objected ways of recruitment.)
Sponsor:
Collaborator:
Technologiestichting STW (NWO)
Information provided by:
Maastricht University Medical Center
ClinicalTrials.gov Identifier:
NCT00826566
First received: January 21, 2009
Last updated: September 17, 2009
Last verified: September 2009
  Purpose

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 Intervention
Chronic Obstructive Pulmonary Disease
Dietary Supplement: Caffeine
Dietary Supplement: placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, 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)

Resource links provided by NLM:


Further study details as provided by Maastricht University Medical Center:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • Oxidative stress markers in plasma such as PGF2alpha [ Time Frame: at the start and the end of the intervention periods ] [ Designated as safety issue: No ]
  • Plasma concentrations of caffeine and metabolites [ Time Frame: at the start and the end of the interventions ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Cytokine concentrations in whole blood after ex vivo stimulation with LPS [ Time Frame: at the start and the end of the interventions ] [ Designated as safety issue: No ]

Estimated Enrollment: 12
Study Start Date: January 2009
Estimated Study Completion Date: September 2009
Estimated Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
caffeine
Dietary Supplement: Caffeine
2 times 250 mg caffeine per day
Placebo Comparator: 2
placebo
Dietary Supplement: placebo
2 times 250 mg per day

  Eligibility

Ages Eligible for Study:   40 Years to 70 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00826566

Locations
Netherlands
Maastricht University Medical Centre (UMC+)
Maastricht, Netherlands, 6200 MD
Sponsors and Collaborators
Maastricht University Medical Center
Technologiestichting STW (NWO)
Investigators
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
  More Information

No publications provided

Responsible Party: Ir. C.H. Kemper, Technologiestichting STW (NWO), PO Box 3021, 3502 GA Utrecht, The Netherlands
ClinicalTrials.gov Identifier: NCT00826566     History of Changes
Other Study ID Numbers: STW6041
Study First Received: January 21, 2009
Last Updated: September 17, 2009
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Maastricht University Medical Center:
COPD
caffeine
chronic systemic inflammation
oxidative stress
supplementation
stable COPD GOLD stage II with CRP levels ≥ 3 mg/l

Additional relevant MeSH terms:
Lung Diseases
Respiration Disorders
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Respiratory Tract Diseases
Anti-Inflammatory Agents
Caffeine
Therapeutic Uses
Pharmacologic Actions
Central Nervous System Stimulants
Physiological Effects of Drugs
Central Nervous System Agents
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Purinergic P1 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents

ClinicalTrials.gov processed this record on July 20, 2014