Primary: 1. To demonstrate migration of circulating white blood cells into atherosclerotic lesions in subjects with atherosclerotic disease via quantification with SPECT.Secondary: 2. To evaluate the relation between FDG-PET signal (reflection of…
ID
Source
Brief title
Condition
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Main study parameters:
The assessment of SPECT images at the site of atherosclerosis, reported as
geometric mean counts per minute per 100 pixels divided by the injected dose of
radioactivity.
Secondary outcome
Secondary study parameters/endpoints
- Association between the degree of monocyte influx/tracer uptake at the site
of atherosclerosis and TBR as measured with FDG-PETCT.
- Association between the degree of monocyte influx/tracer uptake at the site
of atherosclerosis and DCE-MRI signal.
- Association between the degree of monocyte influx/tracer uptake at the site
of atherosclerosis and laboratory parameters; for example but not limited to
inflammatory parameters.
- To evaluate differences between SPECT signal in subjects with cardiovascular
disease and healthy controls.
Background summary
Inflammation has now been widely acknowledged as one of the driving factors
behind the development of (advanced) atherosclerotic plaque and/or clinical
events. Macrophages and T-cells have been shown to accelerate atherosclerotic
plaque development, but data is scarce on actual influx of immune cells into
atherosclerotic lesions in humans. In mice, atherosclerosis drives a rapid
influx of inflammatory monocytes and other immune cells. Once in the vessel
wall, subsets of mononuclear cells differentiate to a phenotype consistent with
inflammatory macrophages. Here, we propose to quantify the influx of
mononuclear cells with SPECT and 99m-Technetium labelling to enhance our
understanding on influx of immune cells into the vascular wall in humans.
Increasing our understanding of a *continuous* influx of new white blood cells
into the vessel wall will have profound implications for strategies aimed at
decreasing this influx of new white blood cells instead of reducing the
*resident* inflammatory cells.
Study objective
Primary:
1. To demonstrate migration of circulating white blood cells into
atherosclerotic lesions in subjects with atherosclerotic disease via
quantification with SPECT.
Secondary:
2. To evaluate the relation between FDG-PET signal (reflection of number and
metabolic activity of macrophages in the vessel wall) and the influx of
circulating white blood cells (SPECT).
3. To evaluate the relation between DCE-MRI (reflection of vessel wall
inflammation) and the influx of circulating white blood cells (SPECT).
4. To evaluate the relation between SPECT signal and plasma levels of
inflammatory markers (e.g. CRP, IL1b)
5. To evaluate differences between SPECT signal in subjects with cardiovascular
disease and healthy controls.
Study design
This study is designed as a single-center, cross-sectional and observational
study.
Patients will undergo a FDG-PETCT scan and DCE-MRI. Within three months after
PET-CT scan and DCE-MRI a scintigraphy of 99mTc-labeled autologous monocytes
will be performed. Subjects will undergo monocytes cell separation, isotopic
labelling with technetium-99m (99mTc) and re-infusion of labelled cells under
the investigator*s supervision. No investigational products will be used in
this study.
Study burden and risks
The results of this study contribute to the development of our understanding on
the roll of immune cells in atherosclerotic diseases. Also, it contributes to
the development of novel anti-inflammatory directed atherosclerotic treatment
strategies. Patients receive no direct benefits.
Meibergdreef 9
Amsterdam 1100DD
NL
Meibergdreef 9
Amsterdam 1100DD
NL
Listed location countries
Age
Inclusion criteria
Healthy controls
* Adults (either gender) * 18 years
* Willing and able to participate in study protocol
Cardiovascular patients
* Adult patients (either gender) * 18 years
* For patients using statins, angiotensin-converting enzyme (ACE) inhibitors (ACE-I) or angiotensin-receptor blockers (ARBs), non-statin lipid-modifying therapy, thiazolidinediones, inhaled steroids, or leukotriene modifying agents; use of a stable dose for at least 6 weeks prior to the first visit.
* Documented * atherosclerotic vascular disease (e.g., CAD, peripheral arterial disease, aortic atherosclerosis or abdominal aortic aneurysm (< 5 cm), carotid disease or cerebrovascular disease) and clinically stable for at least 3 months prior to screening, or or at elevated risk for CVD:
oBMI > 27.
oHDL < 1.0.
oMetabolic syndrome, as defined by the worldwide definition by the International Diabetes Federation criteria.
oDiabetes mellitus type II . ;* Documentation will include one or more of the following: history of myocardial infarction or stroke or, objective diagnostic testing. ( Examples include but are not limited to: Exercise treadmill test, Stress echocardiography, Myocardial perfusion scintigraphy, Right or left common carotid intima-media thickness (CIMT) by ultrasound > 75th percentile by American Society of Echocardiography, Presence of carotid plaque by carotid ultrasound (focal thickening > 50% or CIMT > 1.5 mm), Abdominal aortic aneurysm by CT or ultrasound, Coronary artery calcium score > 100 Agatston units in patients < 60 years of age, CT or conventional coronary or peripheral angiography with at least one moderate or severe luminal stenosis, CT coronary angiography with one or more atherosclerotic plaques demonstrating positive remodeling or hypodense plaque morphology, Moderate or severe aortic atherosclerosis by CT or Transesophageal echocardiography, History of revascularization procedure (e.g., coronary or peripheral arterial bypass grafting, percutaneous coronary or peripheral intervention, carotid endarterectomy).
Exclusion criteria
Healthy controls are not eligible if they meet one of the criteria listed below:
* Any known systemic chronic disorders/medical condition or chronic use of systemic medication that could interfere with the conduct of the study in the opinion of the investigator.
*Standard contra-indications to MRI, PET, and CT.
* Inability or unwillingness to comply with the protocol requirements, or deemed by investigator to be unfit for the study.
Cardiovascular patients are not eligible if they meet one of the criteria listed below:
*Auto-immune disease/vasculitis, other active inflammatory diseases, proven or suspected bacterial infections. Recent (<1 month prior to screening) or ongoing serious infection requiring IV antibiotic therapy that could interfere with the conduct of the study in the opinion of the investigator.
*Known systemic disorders such as hepatic, renal, hematologic, and malignant diseases or any clinically significant medical condition that could interfere with the conduct of the study in the opinion of the investigator.
*Recent (< 1 month prior to screening) or current treatment with medications that may have a significant effect on plaque inflammation as measured by plaque TBR, including: oral, rectal, or injectable corticosteroids or immunosuppressive medications (e.g., cyclosporine, methotrexate, tacrolimus, azathioprine, anti-thymocyte globulin, sirolimus, anti-TNF agents such as infliximab, anti-IL6 therapy such as tocilizumab, or anti-IL1 therapy such as anakinra).
*Poorly controlled diabetes defined as hemoglobin A1c (HbA1c) >7.5% due to inability to comply with recommended diabetes treatment.
*History of anaphylaxis, anaphylactoid (resembling anaphylaxis) reactions, or severe allergic responses.
*Planned cardiac surgery, PCI or carotid stenting, or major non-cardiac surgery during the course of the study period that could interfere with the conduct of the study in the opinion of the investigator.
*Standard contra-indications to MRI, PET, and CT.
*Inability or unwillingness to comply with the protocol requirements, or deemed by investigator to be unfit for the study.
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 | NL41040.018.12 |