The main objectives of this study is to see if changes in the innate immune system can be found in diseases associated with increased risk for atherosclerosis
ID
Source
Brief title
Condition
- Diabetic complications
- Autoimmune disorders
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameters are the trans endothelial migration capability and
subtyping of monocytes in relation to underlying disease (activity).
Secondary outcome
Other important study parameters include epigenetic changes of monocytes and
differences in cytokine production after stimuli.
Background summary
Atherosclerosis is the main cause of cardiovascular disease. It is a
progressive disease, characterized by the formation of plaques in the vessel
wall. After a long asymptomatic period, patients with atherosclerosis can
present with symptoms of impaired blood flow due to stenosis (e.g. stable
angina pectoris, claudicatio intermittens) or with acute complications due to
plaque rupture (e.g. myocardial infarction, ischemic stroke). Many diseases
affecting the immune system are associated with enhanced atherosclerosis,
independent of traditional risk factors. Recent findings indicate the
importance of the innate immune system and monocytes in the development and
progression of atherosclerosis. Several disease entities with a
pro-inflammatory phenotype, such as chronic kidney disease, diabetes,
rheumatoid artritis, Crohn*s disease and psoriasis, are marked by an increased
association with cardiovascular morbidity and mortality. Interestingly, in some
of these diseases, the suggestion has already been made that prolonged activity
of monocytes can be found, even when the stimulus is evaded. Moreover, Recent
data highlights the ability of LDL cholesterol to cause arterial wall
inflammation and monocyte hyperreactivity. Recently, it has been shown that
infection with candida albicans can lead to epigenetic changes on monocytes,
rendering them with increased cytokine production, even when the infection is
long gone.
Study objective
The main objectives of this study is to see if changes in the innate immune
system can be found in diseases associated with increased risk for
atherosclerosis
Study design
This study is designed as a single center, observational study. After screening
for eligibility, all subjects will undergo cardiovascular risk assessment and
laboratory testing. Thereafter assement of transendothelial migration and
monocyte activation will be assessd, as well as epigenetics and in vitro
stimulation assays.
Study burden and risks
The results of this study contribute to the understanding of the involvement of
the innate immune system in atherosclerosis, thereby contributing to risk
stratification in individual patients and testing of new anti-atherosclerotic
treatment. Individual subjects will gain no direct benefit from this study. The
risk of participating in this study is estimated to be low. The patients will
visit the hospital on 1 occasions for medical history, cardiovascular risk
assessment and blood withdrawal with a maximum of 156 ml.
Meibergdreef 9
Amsterdam Zuid Oost 1105 AZ
NL
Meibergdreef 9
Amsterdam Zuid Oost 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
Group A: 40 Healty control subjects
- Aged 18 years or older;Group B: 40 Chronic kidney disease (CKD) patients
- Aged 18 years or older
- 20 CKD stages 3 and 4 (GFR: 15-60 ml min-1) and
- 20 Kidney transplant donors with GFR: 15-60 ml min-1 for a duration of at least 3 months
- Non inflamed (CRP <10);Group C: 20 patients with rheumathoid artritis, currently in remission as assessed by disease activity score <2,6
- Aged 18 years or older
- Non inflamed (CRP <10);Group D: 30 patients with peripheral artery disease defined as: EA-index < 0,9 and validated PAD with echo duplex, divided into 3 groups:
- 10 patients without DM2
- 10 patients with DM2 on oral glucose lowering therapy only
- 10 patients with DM2 on oral glucose lowering therapy and insulin
- Aged 18 years or older
- Non inflamed (CRP <10);Group E:
60 patients with a diagnosis of hypercholesterolemia, consisting of 3 subgroups
- 20 subjects currently not on statin therapy
- 20 subjects on stable statin therapy (at least 3 months) with LDL levels on target
- 20 subjects on stable statin therapy (at least 3 months) with LDL levels not on target
- Aged 18 years or older
- Non inflamed (CRP <10)
Exclusion criteria
Exclusion criteria for all subjects
- Known malignant disorders or any clinically significant medical condition that could interfere with the conduct of the study in the opinion of the investigator.
- Inability or unwillingness to comply with the protocol requirements, or deemed by investigator to be unfit for the study.
- Clinical signs of acute infection and/or CRP>10;Exclusion criteria for group B: Chronic Kidney Disease
- Diabetic nephropathy
- History of MI/Stroke;Exclusion criteria for group C: Rheumatoid artitis
- History of MI/Stroke;Exclusion criteria for group D: Peripheral artery disease
- MI/Stroke in the last 12 months;Exclusion criteria for group E: Hypercholesterolemia
- MI/Stroke in the last 12 months
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 | NL47204.018.13 |