to evaluate the anti-inflammatory effects of 3 months statin therapy on vessel wall inflammation by means of FDG PET/CT in patients with CKD
ID
Source
Brief title
Condition
- Renal disorders (excl nephropathies)
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Change in target-to-background ratio (TBR) in patients with CKD before and
after statin therapy
Secondary outcome
- Monocyte subtyping will be assessed by FACS analysis
- Monocyte expression of genes involved in inflammation
- Trans endothelial migration will be assessed according to standard procedures
at Sanquin as described in van Buul et al (16).
- In vitro cytokine production will be assessed using isolated monocytes of
subjects. Monocytes will be stimulized with LPS, assessing production of
inflammatory cytokines (Il6, TNF*)
- Epigenetic changes will be assessed by looking at H3K4 methylation at target
genes assessed in the previous steps.
Background summary
Atherosclerosis is the main cause of cardiovascular disease. It is an
progressive disease with an inflammatory component, characterized by the
formation of plaques in the arterial wall. After a long asymptomatic period,
patients with atherosclerosis can present with symptoms of impaired blood flow
due to stenosis or with acute complications due to plaque rupture (e.g.
myocardial infarction, ischemic stroke).
Subjects with chronic kidney disease (CKD) have an increased cardiovascular
mortality and acute-phase inflammation. Recently, we observed that patients
with chronic kidney disease (CKD) have a significant increase of arterial wall
inflammation compared with healthy controls matched for gender, age and BMI. A
study by Tawakol et al shows significant and rapid, dose-dependent reductions
in vessel wall FDG uptake, i.e. inflammation by use of statin therapy.
Therefore, our aim is to evaluate the anti-inflammatory effect of statin
therapy in patients with CKD and enhanced vessel wall inflammation. Eventually,
additional treatment or improved treatment of patients, specifically aimed on
the vessel wall inflammation may be justified to decrease mortality rates in
patients with CKD.
Study objective
to evaluate the anti-inflammatory effects of 3 months statin therapy on vessel
wall inflammation by means of FDG PET/CT in patients with CKD
Study design
This is a single centre intervention study. At baseline PET/CT measurements
will be performed. After baseline imaging, all patients with CKD will be
treated with statin therapy for 3 months, after which the PET/CT will be
repeated. Patients who were included in the flame study will start immediately
with statin treatment, since baseline imaging is already performed.
Intervention: All patients with CKD will receive statin therapy after baseline
imaging. Statin therapy will consist of a once daily dosis of 40 mg
Atorvastatine.
Intervention
3 months treatment with atorvastatin 40 mg 1 tablet daily
Study burden and risks
The study consists of 2 study visits and 1 scheduled telephonic appointment.
Patietns will undergo 2 x FDG PET/C scans and 2x venapuncture will be
performed.
Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
1. Aged 50 years or older
2. CKD stages 3 and 4 (eGFR: 15-60 ml min-1)
Exclusion criteria
1. Malignant diseases or any clinically significant medical condition that could interfere with the conduct of the study in the opinion of the investigator.
2. Standard contra-indications to 18F-FDG PET, and CT based on physicians experience and current practices
3. Inability or unwillingness to comply with the protocol requirements, or deemed by investigator to be unfit for the study.
4. Planned radiation exposure in the next year due to participation in a research project with radiation exposure or for clinical reasons.
5. Clinical signs of acute infection and/or CRP>10
6. History of MI/Stroke or known coronary artery disease
7. Already receiving lipid lowering treatment
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 | EUCTR2016-000478-39-NL |
| CCMO | NL56613.018.16 |