The main objective of this study is to assess the effect of elevated remnant cholesterol levels on arterial wall inflammation.
ID
Source
Brief title
Condition
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameters are arterial wall inflammation (target-to-background
ratio) measured by 18F-FDG PET/CT and vessel wall dimensions measured by MRI.
Secondary outcome
- Trans endothelial migration (TEM) of monocytes
- Monocyte subtyping by FACS analysis using a CD14, CD16 and HLA-DR backbone.
- In vitro cytokine production by using isolated monocytes of subjects.
- Epigenetic changes in genes identified with FACS or in vitro stimulation
assays.
Background summary
Recent data show that elevated levels of remnant cholesterol are causally
associated with ischemic heart disease. Remnant cholesterol is the cholesterol
content of triglyceride rich lipoproteins, derived from chylomicrons and very-
low-density-lipoproteins (VLDL). A pathophysiological explanation for the
relationship with ischemic heart disease is that remnants, only slightly bigger
in size than LDL, yet with a higher cholesterol load, can get trapped in the
arterial wall and give rise to foam cell formation and local inflammation.
Importantly, remnants, in contrast to LDL, do not require to be oxidized prior
to macrophage engulfment. Recognizing the key role of systemic inflammation in
atherosclerosis, these particles are also associated with elevated C-reactive
protein (CRP) levels.
18F-FDG PET/CT is a nucleair imaging technique which measures metabolic
activity by labelling glucose with a PET tracer (18-fluor), and is used at a
read-out for the atherosclerotic plaque inflammation.
Study objective
The main objective of this study is to assess the effect of elevated remnant
cholesterol levels on arterial wall inflammation.
Study design
This study is designed as a single centre, observational, case-control study.
After screening for eligibility, all subjects will undergo cardiovascular risk
assessment and laboratory testing. Thereafter, all subjects will undergo
subsequently an 18F-FDG PET/CT scan and MRI scan. Furthermore, trans
endothelial migration (TEM) and monocyte activation will be assessed.
Study burden and risks
The results of this study contribute to better understanding of the mechanism
by which elevated remnant cholesterol causes IHD. This helps us to comprehend
the role of this lipid fraction in cardiovascular disease and the effects of
current treatments in this state as well as design new treatments in the
future. Individual subjects will gain no direct benefit from this study. The
risk of participating in this study is estimated to be low. MRI is a safe
imaging technique without radiation exposure. The exposure to radiation related
to 18F-FDG PET/CT scan is 4.1 mSv.
Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
- Subjects with diagnosis of Familial dysbetalipoproteinemia (type III hyperlipoproteinemia)
- Aged 50 years or older
- No treatment with lipid lowering drugs or willing to stop lipid lowering therapy for 6 weeks prior to baseline measurements
Exclusion criteria
1 . Malignant diseases or any other clinically significant medical condition that could interfere with the conduct of the study in the opinion of the investigator
2 . Standard contra-indications to MRI and 18F-FDG PET/CT based on physicians experience and current practices: Claustrophobia, metal in the body, as a result of e.g. osteosynthetic material, pacemaker implantation of artificial cardiac valves.
3. Clinical signs of acute infection and/or CRP > 10
4 . Participation in a scientific study with radiation exposure in the year prior to inclusion or
planned radiation exposure in the next year due to participation in a research project with radiation exposure or for clinical reasons
5. Recent (< 1 month prior to screening) or current treatment with medications that
may have a significant effect on plaque inflammation, including: oral, rectal, or injectable corticosteroids or immunosuppressive medications
6. Use of lipid lowering drugs in the last 6 weeks prior to baseline measurements
7. Cardiovascular event in the last 3 months prior to baseline measurements
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 | NL52205.018.15 |