Does antagonism of the adenosine receptor by caffeine lead to an increased LPS-induced inflammatory reaction and an increase in (subclinical) tissuedamage?Does the C34T-polymorphism of the enzyme AMP-deaminase lead to a decreased inflammatory…
ID
Source
Brief title
Condition
- Chromosomal abnormalities, gene alterations and gene variants
- Ancillary infectious topics
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Effect on inflammation (temperature, C-reactive protein (crp), white blood
count)
- concentrations of pro- and anti-inflammatory cytokines and adenosine
- vascular (dys)function:
- effects on norepinephrine
- effects on endothelial function
- circulation endothelial cells.
- Renal failure (specific markers for tissue damage)
Secondary outcome
adenosine concentrations
Background summary
Despite maximal antibiotic and supportive therapy the moratality of septic
shock remains 30-50%. Therefore new therapeutic options are needed.
Pathophysiological insights are needed to explore new pharmacotherapeutic
targets. The adnosine receptor is known for its anti-inflammatory actions and
could therefore be a potential target in the treatment of septic shock.
Stimulation of the adenosine receptor could potentially lead to a decrease in
inflammation and tissue damage.
Study objective
Does antagonism of the adenosine receptor by caffeine lead to an increased
LPS-induced inflammatory reaction and an increase in (subclinical) tissuedamage?
Does the C34T-polymorphism of the enzyme AMP-deaminase lead to a decreased
inflammatory respons and thereby a decrease of LPS-induced tissuedamage?
Study design
doubleblind placebo controlled
Intervention
LPS (endotoxin) in three groups
1 group will be treated with caffeine, the other with placebo.
The AMPD1 group will be treated the same way as the placebo group
Study burden and risks
LPS-infusion: Intravenous injection of endotoxin (= LPS) in healthy subjects is
a general accepted model to study inflammation. Worldwide thousands of
volunteers had LPS injected without reports of serious adverse events or
hospitalisation.
Caffeine will be infused in a concentration of 4 mg/kg. There are no health
risks involved in the infusion of caffeine.
Local infusion of norepinephrine, acetylcholine and nitroprusside does not lead
to systemic effects. There are no health risks involved in this infusion.
Total bloodcollection: approximately 350 ml, maximally 400 ml.
Postbus 9101
6500 HB Nijmegen
Nederland
Postbus 9101
6500 HB Nijmegen
Nederland
Listed location countries
Age
Inclusion criteria
Healthy male volunteers (no relevant medical history, no medication)
no history of syncope
age 18-35 years
non-smokers
Exclusion criteria
History of syncope
Design
Recruitment
Medical products/devices used
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 |
|---|---|
| EudraCT | EUCTR2007-002860-86-NL |
| CCMO | NL17473.091.07 |