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Morphological and Serological Criteria of Plaque Vulnerability: Risk Assessment for Symptomatic and Asymptomatic Carotid Artery Stenosis (VUCAP)

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ClinicalTrials.gov Identifier: NCT02124928
Recruitment Status : Unknown
Verified September 2015 by Prim PD Dr Afshin Assadian, Wilhelminenspital Vienna.
Recruitment status was:  Recruiting
First Posted : April 28, 2014
Last Update Posted : September 21, 2015
Sponsor:
Collaborator:
Wilhelminenspital Vienna
Information provided by (Responsible Party):
Prim PD Dr Afshin Assadian, Wilhelminenspital Vienna

Tracking Information
First Submitted Date April 16, 2014
First Posted Date April 28, 2014
Last Update Posted Date September 21, 2015
Study Start Date September 2012
Estimated Primary Completion Date December 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: April 24, 2014)
serum levels of PEDF, VEGF, HIF-1 alpha, MMP-2, -8 and -9 compared to histomorphological classification of the plaque based on AHA classification and ultrasonographic data- grey scale median (GSM) [ Time Frame: ultrasonographical data are assessed a day before the surgery, carotid artery plaque will be taken during the surgery, whole blood on the day of operation, ]
Extended sonomorphological investigation will be performed by a sonographer blinded to patients' characteristics, for the assessment of grey scale median (GSM). After removal plaques will be fixated in RNAlater for further RNA-determinations. In addition, histomorphological characterization of the plaque will be performed and the plaque classified based on the American Heart Association (AHA) classification. RNA-determination will focus on the expression levels of PEDF. VEGF, HIF-1 alpha, MMP-2, -8 and -9. For that purpose we will perform RNA isolation from the tissue, transcription to cDNA and also a quantitative real-time PCR. Furthermore immunostaining of the plaque with PEDF, VEGF, HIF-1 alpha, MMP-2, -8 and -9 antibodies to determine the distribution of those proteins within the plaques will be done.
Original Primary Outcome Measures Same as current
Change History Complete list of historical versions of study NCT02124928 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures
 (submitted: April 24, 2014)
change in blood serum levels as well as protein level expression of PEDF, VEGF, HIF-1 alpha, MMP-2, -8 and -9 after plaque removal [ Time Frame: serum blood levels are evaluated from the whole blood twice: on the day of surgery and 6 weeks after removal of the plaque ]
enzyme-linked immunosorbent assay (ELISA) will be done for the determination of PEDF, VEGF, HIF-1 alpha, before and after surgery
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures
 (submitted: April 24, 2014)
composite end point of death, stroke, myocardial infarction [ Time Frame: From date of randomization until the date of first documented or date of death from any cause assessed up to 5 years ]
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title Morphological and Serological Criteria of Plaque Vulnerability: Risk Assessment for Symptomatic and Asymptomatic Carotid Artery Stenosis
Official Title Morphological and Serological Criteria of Plaque Vulnerability: Risk Assessment for Symptomatic and Asymptomatic Carotid Artery Stenosis
Brief Summary The aim of this study is to investigate the association of sonographic and histological features of the plaque among each other and with biomarkers of cardiovascular risk. The predictive value of these factors concerning the long-term clinical outcome after carotid endarterectomy will also be assessed. This may help to improve the identification of patients with carotid artery stenosis who will benefit most from carotid endarterectomy. The investigators major hypothesis is that the morphology of carotid plaques is associated with objectifiable sonographic parameters, in particular with the greyscale median. Second, the investigators hypothesize that sonographic and histological plaque morphology are associated with certain biomarkers of cardiovascular risk. Identification of 'vulnerable plaques' on the basis of a peripheral blood draw and a sonographic investigation may enable the treating physician to focus resources on patients who will benefit most form therapeutic interventions for primary prevention of ischemic stroke.
Detailed Description

The indication for revascularization of carotid artery stenoses is typically based on the degree of stenosis and the presence of symptoms. Recent evidence suggests that the risk of embolization from an atherosclerotic plaque may be associated with plaque density as assessed sonographically by determination of the greyscale median. Also, an association of serum proteins vascular endothelial growth factor (VEGF), hypoxia inducible factor (HIF) and pigment epithelium-derived factor (PEDF), matrix metalloproteinases 2, 8 and 9 with unstable plaques has been reported.

The VUCAP study will include patients undergoing carotid endarterectomy for symptomatic or asymptomatic carotid artery disease. Sonographic and serological markers of plaque vulnerability will be compared with histological features of the plaque and clinical presentation (symptomatic vs. asymptomatic). Preoperatively, the greyscale median of the plaque is assessed. Histomorphological investigation of the carotid plaques will be performed. Serological investigations will include markers of inflammation, thrombo-modulatory factors, lipid fractions and other parameters that have been associated with unstable plaques.

The aim of the present study is to assess the ability of pigment epithelium-derived factor (PEDF), vascular endothelial growth factor (VEGF), hypoxia-induced factor 1 alpha (HIF 1-α), matrix metalloproteinases 2, 8 and 9 to differentiate between vulnerable and stable carotid artery plaques. Identification of 'vulnerable plaques' on the basis of a peripheral blood draw and a sonographic investigation may enable the treating physician to focus resources on patients who will benefit most form therapeutic interventions for primary prevention of ischemic stroke.

Study Type Observational
Study Design Observational Model: Case-Only
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
whole blood serum carotid artery plaque
Sampling Method Probability Sample
Study Population Four hundred patients with symptomatic or asymptomatic carotid artery stenosis undergoing carotid endarterectomy, after written informed consent will be included in this study. The inclusion would be done through our ambulatory care clinic.
Condition
  • Atherosclerosis
  • Carotid Artery Disease
Intervention Procedure: Carotid endarterectomy
Carotid endarterectomy is a surgery used to reduce the risk of stroke, by correcting stenosis in the carotid artery. Endarterectomy is the removal of material on the inside (end-) of an artery.An incision is made on the midline side of the Sternocleidomastoid muscle. The incision is between 5 and 10 cm in length. Then the patients get 5000 IU heparin by the anesthesia. The internal, common and external carotid arteries are carefully identified, controlled with vessel loops, and clamped. The lumen of the internal carotid artery is opened, and the atheromatous plaque removed. The artery is closed using suture. The procedure is performed under local anesthesia. Local anesthesia, opposite to general, allows for direct monitoring of neurological status by intra-operative verbal contact and testing of grip strength.
Study Groups/Cohorts carotid artery stenosis
Patients with symptomatic or asymptomatic carotid artery stenosis indicated for carotid endarterectomy, who provide written informed consent, will be included in this study. The investigators will compare patients ultrasonographic data, serum laboratory analyses and histomorphological preferances to look for biomarkers for the plaque instability.
Intervention: Procedure: Carotid endarterectomy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Unknown status
Estimated Enrollment
 (submitted: April 24, 2014)
400
Original Estimated Enrollment Same as current
Estimated Study Completion Date December 2017
Estimated Primary Completion Date December 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • asymptomatic stenosis of internal carotid artery >70%
  • symptomatic stenosis of internal carotid artery >60%
  • planed surgical treatment of the stenosis

Exclusion Criteria:

  • pregnancy
  • symptomatic coronary heart disease
  • myocardial infarction or acute coronary syndrome in the past 3 months
  • acute peripheral artery occlusion in the past 3 months
  • immaturity
  • existence of a guardianship
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries Austria
Removed Location Countries  
 
Administrative Information
NCT Number NCT02124928
Other Study ID Numbers VUCAP
EK-11-208-VK ( Other Identifier: Ethics committee Vienna )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Prim PD Dr Afshin Assadian, Wilhelminenspital Vienna
Study Sponsor Prim PD Dr Afshin Assadian
Collaborators Wilhelminenspital Vienna
Investigators
Principal Investigator: Afshin Assadian, Prim PD Dr Georg Hagmüller Institute for Vascular Research Wilheminenspital Vienna, Austria
PRS Account Wilhelminenspital Vienna
Verification Date September 2015