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Local delivery of CER-001 in advanced plaques Proof-of-concept for apoA-1 as initiator of reverse cholesterol transport


- candidate number22174
- NTR NumberNTR5178
- ISRCTNISRCTN no longer applicable
- Date ISRCTN created
- date ISRCTN requested
- Date Registered NTR6-mei-2015
- Secondary IDsNL49081.018.14; 2014-001666-10 ABR; EudraCT
- Public TitleLocal delivery of CER-001 in advanced plaques Proof-of-concept for apoA-1 as initiator of reverse cholesterol transport
- Scientific TitleLocal delivery of CER-001 in advanced plaques Proof-of-concept for apoA-1 as initiator of reverse cholesterol transport
- ACRONYMLOCATION
- hypothesisTo demonstrate that 89Zr-CER-001 penetrates into atherosclerotic plaques in patients by means of PET imaging.
- Healt Condition(s) or Problem(s) studiedAtherosclerose, Cardiovascular disease
- Inclusion criteriaPatients must meet the following criteria for study entry:
- Adult patients (either gender) ≥ 50 years
- Documented atherosclerotic vascular disease; defined as either peripheral arterial disease or documented aortic or carotid atherosclerosis on clinical vascular MRI or ultrasound
- Clinically stable for at least 3 months prior to inclusion
- Very high CV-risk (based on Framingham risk engine)
- Exclusion criteriaPatients are not eligible if they meet one of the criteria listed below:
- Creatinine clearance < 50 ml/min (MDRD) 6 months prior to inclusion
- Auto-immune disease/vasculitis, other active inflammatory diseases, proven or suspected bacterial infections. Recent (<1 month prior to inclusion) 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
- 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
- mec approval receivedyes
- multicenter trialno
- randomisedno
- group[default]
- TypeSingle arm
- Studytypeobservational
- planned startdate 22-jul-2014
- planned closingdate1-jan-2016
- Target number of participants8
- InterventionsInfusion with (89Zr-)CER-001 and PET-CT imaging
- Primary outcomeThe CER-001 uptake in the plaque over time by means of PET imaging of the aorta and carotid arteries, reported as Standardized Uptake Value (SUV) of the plaque
- Secondary outcomeFurther quantification of CER-001 uptake at the plaque
- 89Zr-CER-001 uptake in the plaque over time assessed as the Target to Background Ratio (TBR), via PET imaging
- Difference between SUV and TBR at the level of the plaque and SUV and TBR of non-diseased arterial wall on PET

Relation between CER-001 uptake and plaque characteristics
- Relation between SUV and TBR of the plaque on PET and structural plaque dimensions on MRI i.e. normalized wall index, vessel wall area. - Relation between SUV and TBR of the plaque and plaque permeability on DCE-MRI, i.e. Ktrans

Relationship between the CER-001 uptake in the plaque by means of PET imaging reported as SUV of the plaque and the cholesterol efflux capacity.
- TimepointsPET/CT scans will be performed at timepoints 10 minutes, 24 hours and 72 hours after 89Zr-CER-001 infusion.
- Trial web siten/a
- statusstopped: trial finished
- CONTACT FOR PUBLIC QUERIESMD K.H. Zheng
- CONTACT for SCIENTIFIC QUERIESMD K.H. Zheng
- Sponsor/Initiator Academic Medical Center (AMC), Amsterdam
- Funding
(Source(s) of Monetary or Material Support)
Academic Medical Center (AMC)
- Publications
- Brief summaryAtherosclerosis is considered a chronic inflammatory disease in which macrophages play a major role by taking up (oxidized) low-density lipoprotein (LDL). The lipid-laden macrophages accumulate and undergo apoptosis leading to the formation of a necrotic core and eventually the vulnerable plaque. Cholesterol efflux from lipid-laden macrophages is a key atheroprotective mechanism, a process referred to as reverse cholesterol transport (RCT) in which apolipoprotein (apo)A-1 and HDL particles remove cholesterol from peripheral cells. In view of the abundant evidence for apoA-1 on stimulating efflux from macrophages in vitro, it is reasonable to assume that apoA-1 will also stimulate efflux from vessel wall macrophages in vivo if apoA-1 succeeds in getting into the proximity of plaque macrophages. The radio-isotope Zirconium-89 (89Zr) has emerged as a ‘gold-standard’ in the field of antibody-based PET imaging. The experience in oncology and the fact that 89Zr-labeling is a GMP-approved method makes this a suitable candidate for proving target delivery of apoA-1/HDL into advanced atherosclerotic plaques in humans using non-invasive imaging techniques. With this project we aim to show that exogenously infused apoA-1 (CER-001®) penetrates into advanced plaques in patients, making it ‘highly likely’ that efflux of cholesterol from macrophages to the apoA-1/HDL complex will occur.
- Main changes (audit trail)
- RECORD6-mei-2015 - 12-mrt-2016


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