Anti-inflammatory Effects of Caffeine in Chronic Obstructive Pulmonary Disease (COPD) Subjects
This study has been withdrawn prior to enrollment.
(Suitable subjects could not be recruited within the estimated time frame and via the objected ways of recruitment.)
Sponsor:
Maastricht University Medical Center
Collaborator:
Technologiestichting STW (NWO)
Information provided by:
Maastricht University Medical Center
ClinicalTrials.gov Identifier:
NCT00826566
First received: January 21, 2009
Last updated: September 17, 2009
Last verified: September 2009
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Purpose
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 | Intervention |
|---|---|
|
Chronic Obstructive Pulmonary Disease |
Dietary Supplement: Caffeine Dietary Supplement: placebo |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Caregiver, 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) |
Resource links provided by NLM:
Further study details as provided by Maastricht University Medical Center:
Primary Outcome Measures:
- 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 ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- 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 ] [ Designated as safety issue: No ]
- Oxidative stress markers in plasma such as PGF2alpha [ Time Frame: at the start and the end of the intervention periods ] [ Designated as safety issue: No ]
- Plasma concentrations of caffeine and metabolites [ Time Frame: at the start and the end of the interventions ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
- Cytokine concentrations in whole blood after ex vivo stimulation with LPS [ Time Frame: at the start and the end of the interventions ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 12 |
| Study Start Date: | January 2009 |
| Estimated Study Completion Date: | September 2009 |
| Estimated Primary Completion Date: | June 2009 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: 1
caffeine
|
Dietary Supplement: Caffeine
2 times 250 mg caffeine per day
|
|
Placebo Comparator: 2
placebo
|
Dietary Supplement: placebo
2 times 250 mg per day
|
Eligibility| Ages Eligible for Study: | 40 Years to 70 Years |
| Genders 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00826566
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
No publications provided
| Responsible Party: | Ir. C.H. Kemper, Technologiestichting STW (NWO), PO Box 3021, 3502 GA Utrecht, The Netherlands |
| ClinicalTrials.gov Identifier: | NCT00826566 History of Changes |
| Other Study ID Numbers: | STW6041 |
| Study First Received: | January 21, 2009 |
| Last Updated: | September 17, 2009 |
| Health Authority: | Netherlands: The Central Committee on Research Involving Human Subjects (CCMO) |
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 Respiration Disorders Pulmonary Disease, Chronic Obstructive Lung Diseases, Obstructive Respiratory Tract Diseases Anti-Inflammatory Agents Caffeine Therapeutic Uses Pharmacologic Actions Central Nervous System Stimulants |
Physiological Effects of Drugs Central Nervous System Agents Phosphodiesterase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Purinergic P1 Receptor Antagonists Purinergic Antagonists Purinergic Agents Neurotransmitter Agents |
ClinicalTrials.gov processed this record on May 23, 2013