Main objective is to test if the pharmacogenetic profile that is associated with a decreased response to ACE inhibitor therapy influences the bradykinin B1 receptor induced inflammatory response.
ID
Source
Brief title
Condition
- Coronary artery disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Change in gene-expression of inflammatory genes in response to bradykinin B1
receptor stimulation in human mononuclear cells in the presence or absence of
the rs12050217 minor allele.
Secondary outcome
Secondary study parameters are to test if the inflammatory response is
influenced by stimulation or inhibition of other components of the RAS or kinin
system and evaluation of the plasma for the presence of inflammatory cytokines
and RAS hormones. In addition, genetic analysis of other SNP*s in the RAS and
kinin system in relation to the inflammatory response is also a secondary
measurement.
Background summary
To better predict the treatment benefit of angiotensin converting enzyme (ACE)
inhibitor therapy our research group conducted a pharmacogenetic analysis of
genes selected from the renin angiotensin system (RAS) and kinin system in a
placebo controlled ACE inhibitor study with coronary heart disease (CHD)
patients. In this study an association was discovered between treatment benefit
from the ACE inhibitor Perindopril and a single nucleotide polymorphism (SNP)
in the bradykinin B1 receptor gene. The bradykinin B1 receptor is present on a
large variety of cells, including endothelial cells, smooth muscle cells and
leukocytes. Bradykinin B1 receptor expression is low in normal healthy tissue,
but is upregulated during inflammatory events. It has been shown that receptor
stimulation induces an increase in inflammatory cytokines and also that
inflammatory cytokines upregulate B1 receptor expression. Use of ACE inhibitors
is associated with a potentiation of the substrates for bradykinin receptors,
therefore we hypothesize that the presence of the pharmacogenetic profile
influences the inflammatory response to bradykinin B1 receptor stimulation.
To test this hypothesis we would like to investigate in mononuclear cells,
isolated from blood of healthy volunteers, if the pharmacogenetic profile
earlier discovered is of influence on the inflammatory response to bradykinin
B1 stimulation.
Study objective
Main objective is to test if the pharmacogenetic profile that is associated
with a decreased response to ACE inhibitor therapy influences the bradykinin B1
receptor induced inflammatory response.
Study design
Single blood donation of 20 ml to isolate human mononuclear cells, in which the
response to bradykinin B1 receptor stimulation will be tested.
Study burden and risks
Burden and risk for participating in the study are low, subjects are asked to
donate 4 tubes of blood (20ml in total) and a few general questions are asked
about age, gender and if the subjects use any medication.
Dr. Molewaterplein 50
3015 GE Rotterdam
NL
Dr. Molewaterplein 50
3015 GE Rotterdam
NL
Listed location countries
Age
Inclusion criteria
Healthy persons within the age group of 18-60 years.
Exclusion criteria
Use of ACE inhibitors, AT1 receptor blocker or renin inhibitor.
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 | NL38754.078.12 |