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

Primary Purpose

Chronic Obstructive Pulmonary Disease

Status

Withdrawn

Phase

Not Applicable

Locations

Netherlands

Study Type

Interventional

Intervention

Caffeine

placebo

About this trial

This is an interventional prevention trial for Chronic Obstructive Pulmonary Disease focused on measuring COPD, caffeine, chronic systemic inflammation, oxidative stress, supplementation, stable COPD GOLD stage II with CRP levels ≥ 3 mg/l

Eligibility Criteria

40 Years - 70 Years (Adult, Older Adult)MaleDoes not accept healthy volunteers

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).

Sites / Locations

Maastricht University Medical Centre (UMC+)

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Arm Description

500 mg caffeine capsules per day

500 mg placebo capsules

Outcomes

Primary Outcome Measures

Plasma concentrations of C-reactive protein (CRP) and the cytokines TNF-a, IL-6, IL-8 and IL-10.

Secondary Outcome Measures

Activation of poly-(ADP-ribose) polymerase (PARP)-1 activation and DNA repair in peripheral lymphocytes

Oxidative stress markers in plasma such as PGF2alpha

Plasma concentrations of caffeine and metabolites

Gene transcription levels of cytokines, redox enzymes and other proteins involved in inflammatory and oxidative stress response

Cytokine concentrations in whole blood after ex vivo stimulation with LPS

Full Information

NCT ID

NCT00826566

First Posted

January 21, 2009

Last Updated

September 22, 2015

Sponsor

Maastricht University Medical Center

Collaborators

Technologiestichting STW (NWO)

1. Study Identification

Unique Protocol Identification Number

NCT00826566

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2009

Overall Recruitment Status

Withdrawn

Why Stopped

Suitable subjects could not be recruited within the estimated time frame.

Study Start Date

January 2009 (undefined)

Primary Completion Date

June 2009 (Anticipated)

Study Completion Date

September 2009 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Maastricht University Medical Center

Collaborators

Technologiestichting STW (NWO)

4. Oversight

Data Monitoring Committee

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Obstructive Pulmonary Disease

Keywords

COPD, caffeine, chronic systemic inflammation, oxidative stress, supplementation, stable COPD GOLD stage II with CRP levels ≥ 3 mg/l

7. Study Design

Primary Purpose

Prevention

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Active Comparator

Arm Description

500 mg caffeine capsules per day

Arm Title

Arm Type

Placebo Comparator

Arm Description

500 mg placebo capsules

Intervention Type

Dietary Supplement

Intervention Name(s)

Caffeine

Intervention Description

2 times 250 mg caffeine per day

Intervention Type

Dietary Supplement

Intervention Name(s)

placebo

Intervention Description

2 times 250 mg per day

Primary Outcome Measure Information:

Title

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 Measure Information:

Title

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

Title

Oxidative stress markers in plasma such as PGF2alpha

Time Frame

at the start and the end of the intervention periods

Title

Plasma concentrations of caffeine and metabolites

Time Frame

at the start and the end of the interventions

Title

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

Title

Cytokine concentrations in whole blood after ex vivo stimulation with LPS

Time Frame

at the start and the end of the interventions

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

40 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility 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).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Geja J Hageman, PhD

Organizational Affiliation

Dept. of Health Risk Analysis and Toxicology, UMC+, Maastricht, The Netherlands

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Antje R Weseler, PhD

Organizational Affiliation

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

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Aalt Bast, PhD, Prof.

Organizational Affiliation

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

Official's Role

Study Director

Facility Information:

Facility Name

Maastricht University Medical Centre (UMC+)

City

Maastricht

ZIP/Postal Code

6200 MD

Country

Netherlands

12. IPD Sharing Statement

Learn more about this trial

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

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