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

Pilot Study to Investigate the Anti-inflammatory Effects of Caffeine in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

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.

Study Overview

• Status: Withdrawn
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Dietary supplement: Caffeine; Dietary supplement: placebo

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Maastricht, Netherlands, 6200 MD
    • Maastricht University Medical Centre (UMC+)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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
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

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Collaborators: 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

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (ANTICIPATED): June 1, 2009
• Study Completion (ANTICIPATED): September 1, 2009

Study Registration Dates

• First Submitted: January 21, 2009
• First Submitted That Met QC Criteria: January 21, 2009
• First Posted (ESTIMATE): January 22, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): September 23, 2015
• Last Update Submitted That Met QC Criteria: September 22, 2015
• Last Verified: September 1, 2009

More Information

Terms related to this study

• Keywords: COPD; caffeine; supplementation; oxidative stress; chronic systemic inflammation; stable COPD GOLD stage II with CRP levels ≥ 3 mg/l
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Purinergic Antagonists; Purinergic Agents; Phosphodiesterase Inhibitors; Purinergic P1 Receptor Antagonists; Central Nervous System Stimulants; Caffeine
• Other Study ID Numbers: STW6041