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

Chronic Obstructive Pulmonary Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00826566
• Other study ID #: STW6041
• Status: Withdrawn
• Phase: N/A
• First received: January 21, 2009
• Last updated: September 22, 2015
• Start date: January 2009
• Est. completion date: September 2009

Study information

• Verified date: September 2009
• Source: Maastricht University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: September 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 40 Years to 70 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Dietary Supplement:
• Caffeine
2 times 250 mg caffeine per day
• placebo
2 times 250 mg per day

Locations

Country	Name	City	State
Netherlands	Maastricht University Medical Centre (UMC+)	Maastricht

Sponsors (2)

Lead Sponsor	Collaborator
Maastricht University Medical Center	Technologiestichting STW (NWO)

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	Oxidative stress markers in plasma such as PGF2alpha		at the start and the end of the intervention periods	No
Secondary	Plasma concentrations of caffeine and metabolites		at the start and the end of the interventions	No
Secondary	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	No
Secondary	Cytokine concentrations in whole blood after ex vivo stimulation with LPS		at the start and the end of the interventions	No