To evaluate the potential attenuating effects of a one-week supplementation with 2 x 250 mg caffeine per day on blood biomarkers of systemic inflammation in COPD patients.
ID
Source
Brief title
Condition
- Respiratory disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objective of the present study is to investigate the effects of a
one-week daily supplementation of COPD patients with 2 x 250mg caffeine on
biomarkers of systemic inflammation in blood such as C-reactive protein (CRP)
and the cytokines TNF-a, IL-6, IL-8 and IL-10.
Secondary outcome
The secondary objectives of the study are
1) to investigate the effects of the one week caffeine supplementation on
activation of poly-(ADP-ribose) polymerase I (PARP-I) and DNA-repair in
peripheral blood lymphocytes by means of immune histochemical methods and the
COMET assay. The COMET assay determines the level of DNA strand breaks, and is
indicative for the amount of oxidative DNA lesions.
2) to investigate the effects of the one week caffeine supplementation on
oxidative stress markers in urine such as the ratio of uric acid/allantoin (the
oxidative metabolite of uric acid) and the creatinine levels
3) to determine the levels of caffeine and its metabolites in plasma and urine
4) to investigate the effects of the caffeine supplementation on organic
volatiles (e.g. ethane, pentane and other (unknown) compounds that might be
discriminatory for COPD patients) in exhaled air
5) to investigate the effects of the caffeine supplementation on the cytokine
levels (TNF-a, IL-6, IL-8 and IL-10) in whole blood stimulated ex vivo with
LPS.
6) to investigate the effects of the caffeine supplementation on the gene
expression levels of cytokines, redox enzymes and other proteins involved in
the inflammatory and oxidative stress response
Background 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 (and its metabolites).
Study objective
To evaluate the potential attenuating effects of a one-week supplementation
with 2 x 250 mg caffeine per day on blood biomarkers of systemic inflammation
in COPD patients.
Study design
Double blind, randomised placebo controlled cross-over study
Intervention
According to the cross-over design, the study comprises two intervention
periods of one week which are separated by a wash-out period of three weeks.
Subjects will participate in a one-week run-in period preceding the two
intervention periods, during which they will be asked to replace their usual
coffee consumed throughout the day by a decaffeinated coffee and tea provided
by the investigators. Furthermore, they will be requested to abstain from any
caffeine-containing foods and drinks. Maintenance of this dietary restriction
is also required during both intervention periods.
Generally subjects will be asked not to change their usual dietary and
lifestyle habits throughout the entire trial.
It will be determined by random in which order subjects will receive the verum
and the placebo treatment. Caffeine will be applied in hard gelatine capsules
containing 250 mg (plus an appropriate amount of bulking agent, ih required).
The placebo capsules will solely contain the bulking agent of the verum
medication.
Subjects will be instructed to take twice a day one capsule in the morning and
at lunchtime.
Prior to the beginning of the study subjects will be invited for an initial
visit with instructions on the implementation of a caffeine-free diet and the
supply of the decaffeinated coffee and tea.
During the study subjects will attend four further visits at the
investigational site, which take about 30 min. and will comprise an interview
with the investigator about all study related issues. In addition, on these
occasions 33 ml blood will be collected as well as a sample of exhaled air and
freshly voided urine.
Including the screening subjects will be requested to attend six study visits
at the investigational site.
Study burden and risks
No major risks will be associated with the intake of the investigational
products. Caffeine is a compound of the normal diet and will be administered in
a safe and responsible dose and manner.
There will be two periods each of two weeks during which the subjects will be
requested to replace their usual consumed coffee and tea by decaffeinated
coffee and tea provided by the investigator. However, subjects receive useful
tips and instructions how to avoid caffeine intake from other dietary sources
including caffeine-free alternatives. For this purpose they will be invited to
participate in an additional visit prior to the start of the study.
Throughout the study period (six weeks) subjects will attend in total four
visits at the investigational site of ca. 30 min. During these visits they will
have an interview with the investigator about their well-being, the occurrence
of any adverse events and any questions or problems related to their
participation in the trial. Then heart rate and blood pressure will be
controlled.
33 ml blood will be collected as well as a specimen of exhaled air and freshly
voided urine. Over the entire study period (incl. the screening) subjects will
attend six study visits. In total 138 ml blood will be collected per subject.
Altogether the investigators consider the burden of the subjects as low.
Whether the one-week consumption of caffeine may result in an improvement of
any individual symptoms of the disease cannot be predicted. Participation is
thus not related to any advantage or disadvantage for the individual subject's
health.
PO Box 3021
3502 GA Utrecht
Nederland
PO Box 3021
3502 GA Utrecht
Nederland
Listed location countries
Age
Inclusion criteria
Male subjects in an age of 40-70 years
BMI > 20 kg/m2 and < 30 kg/m2
Diastolic blood pressure (DBP)=60-90 mmHg, Systolic blood pressure (SBP)=100-150 mmHg
CRP-levels > 3mg/l
No acute and/or chronic inflammatory condition such as arthritis, arthrosis, chronic colitis, etc. during three months before entry of the study
No respiratory tract infection or exacerbation of COPD for at least 8 weeks prior to the start of the study
No change in treatment regime of the COPD subjects for at least 8 weeks prior to the start of the study
Normal constant dietary eating habits and a usual coffee consumption of at least 3 cups per day
Non-smokers and stopped smoking, respectively
Exclusion criteria
Women
age < 40 years or > 70 years old
BMI <= 20 kg/m2 and >= 30 kg/m2
Diastolic blood pressure (DBP) < 60 or > 90 mmHg, systolic blood pressure (SBP) <100 or >150 mmHg
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 during the last 8 weeks prior to the start of the study
Change in treatment regime of the COPD subjects during the last 8 weeks prior to the start of the study
Irregular eating habits, usual coffee consumption of less than 3 cups per day and current smoker
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL18785.068.07 |