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

NCT00826566 | Withdrawn

• 1 other identifier: STW6041
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• 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

Study Arms (2)

1

ACTIVE COMPARATOR

500 mg caffeine capsules per day

Dietary Supplement: Caffeine

2

PLACEBO COMPARATOR

500 mg placebo capsules

Dietary Supplement: placebo

Interventions

Caffeine DIETARY_SUPPLEMENT

2 times 250 mg caffeine per day

1

placebo DIETARY_SUPPLEMENT

2 times 250 mg per day

2

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Maastricht University Medical Center: lead
• Technologiestichting STW (NWO): collaborator

Study Sites (1)

Maastricht University Medical Centre (UMC+)

Maastricht, 6200 MD, Netherlands

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Caffeine

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Xanthines; Alkaloids; Heterocyclic Compounds; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

• Aalt Bast, PhD, Prof.

  Dept. of Pharmacology & Toxicology, UMC+, Maastricht, The Netherlands

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2009
• First Posted: January 22, 2009
• Study Start: January 1, 2009
• Primary Completion: June 1, 2009
• Study Completion: September 1, 2009
• Last Updated: September 23, 2015

Record last verified: 2009-09

Locations

NL (1)