To assess the degree of arterial wall inflammation as measured by 18F-FDG PET/CT in subjects with OSAS and to further elucidate the pathophysiological mechanisms responsible for the increase in atherosclerosis in these patients.
ID
Source
Brief title
Condition
- Coronary artery disorders
- Upper respiratory tract disorders (excl infections)
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameter is the measurement of arterial wall inflammation
(target-to-background ratio).
Secondary outcome
* To assess the degree of splenic and bone-marrow metabolic activity as
measured by 18F-FDG PET/CT in subjects with severe OSAS compared to matched
controls with mild OSAS
* To determine the quantity of *intermediate* monocytes in subjects with severe
OSAS compared to matched controls with mild OSAS
* To assess the results of pulse wave velocity (PWV) measurement using
SphygmoCor and MAP, CO, SV, SVR and xBRS values measured with Nexfin® in
subjects with severe OSAS compared to matched controls with mild OSAS and to
assess these variables for potential correlations with 18F-FDG PET/CT data or
data from other measurements
* To assess the correlation between the 18F-FDG PET/CT measurements and
circulating markers of inflammation
* To assess the correlation between the (relative) quantity and phenotype of
circulation blood monocytes
* To assess the difference in priming of NETosis of isolated circulating
neutrophils in subjects with severe OSAS compared to matched controls with mild
OSAS and potential correlations with other outcomes
* To assess the difference in epigenetic modifications in isolated monocytes
and/or other cell types in subjects with severe OSAS compared to matched
controls with mild OSAS and potential correlations with other outcomes
Background summary
Atherosclerosis, the main cause of cardiovascular disease, is a progressive
disease, 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 (e.g. stable angina pectoris,
claudicatio intermittens) or with acute complications due to plaque rupture
(e.g. myocardial infarction, ischemic stroke). OSAS has been associated with
both a higher cardiovascular disease incidence and the metabolic syndrome. In
addition, patients with OSAS are at an increased risk of *stroke and death*.
Earlier studies have shown that patients with OSAS present with higher
sympathetic activity as well as systemic inflammation, the later reflected in
higher levels of CRP. In mice, an increase in sympathetic activity has been
linked to an increased atherosclerotic burden, through an increase in specific
subsets of monocytes. Finally, in humans, 18F-FDG PET/CT has been used to
determine both atherosclerotic burden as well as activation of the bone-marrow
post-myocardial infarction.
Therefore, we expect the sympathetic hyperactivity in these OSAS patients to
lead to an increase in specific cells responsible for the accelerated
generation of atherosclerosis. We expect to visualise this by measurements of
arterial wall inflammation by 18F-FDG PET/CT and expressed as
target-to-background ratios. Additionally, by measuring sympathetic activity,
peripheral blood cells and their phenotype, and the activity of the bone-marrow
and spleen by 18F-FDG-PET/CT, we expect to further validate our hypothesis.
Study objective
To assess the degree of arterial wall inflammation as measured by 18F-FDG
PET/CT in subjects with OSAS and to further elucidate the pathophysiological
mechanisms responsible for the increase in atherosclerosis in these patients.
Study design
This study is designed as a multicentre, observational study. After screening
for eligibility, all subjects will undergo cardiovascular risk assessment,
Nexfin® and pulse-wave velocity measurement and laboratory testing. Afterwards,
subjects will undergo an 18F-FDG PET/CT scan.
Study burden and risks
Radiation exposure, minor discomfort due to extra testing. Given the low risks
of this study and the valuable information which can be obtained relating to
the pathophysiology of cardiovascular disease in this population at a higher
risk of cardiovascular disease, the risks/burden of this study are in
proportion to the intended goals of this study, in my opinion.
Meibergdreef 9
Amsterdam-Zuidoost 1105 AZ
NL
Meibergdreef 9
Amsterdam-Zuidoost 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
1. Age >50 years
2. AHI>30 or AHI <15 depending on group
3. Symptoms matching the diagnosis of OSAS for at least 6 months
4. OSAS as diagnosed by polysomnography
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. Chronic or recent (<1 month) infections and/or clinical signs of acute
infection and/or CRP >10 mg/L
3. Auto-immune diseases
4. Recent or chronic immunosuppressant or antibiotic usage
5. Type I or II diabetes mellitus
6. Smoking or alcohol abuse
7. Sleeping disorder other than OSAS
8. Standard contra-indications to 18F-FDG PET, and CT based on physicians
experience and current practices
9. Exposure to radiation in a different study
10. History of MI/Stroke or known coronary artery diseas
11. BMI >40 kg/m2
12. Weight above 190kg, diameter >69cm (limits CT scanner)
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 | NL58237.018.16 |