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

• ClinicalTrials.gov Identifier: NCT00826566
• Recruitment Status: Withdrawn
• First Posted: January 22, 2009
• Last Update Posted: September 23, 2015
• Sponsor: Maastricht University Medical Center
• Collaborator: Technologiestichting STW (NWO)
• Information provided by (Responsible Party): Maastricht University Medical Center

Study Description

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

Study Design

• 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

Arms and Interventions

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

Outcome Measures

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 ]

Eligibility Criteria

• Ages Eligible for Study: 40 Years to 70 Years (Adult, Older Adult)
• Sexes 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

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

• Responsible Party: Maastricht University Medical Center
• ClinicalTrials.gov Identifier: NCT00826566
• Other Study ID Numbers: STW6041
• First Posted: January 22, 2009
• Last Update Posted: September 23, 2015
• Last Verified: September 2009

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; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Diseases; Caffeine; 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