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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Wilhelminenspital Vienna
Sponsor:
Collaborator:
Wilhelminenspital Vienna
Information provided by (Responsible Party):
Prim PD Dr Afshin Assadian, Wilhelminenspital Vienna
ClinicalTrials.gov Identifier:
NCT02124928
First received: April 16, 2014
Last updated: April 24, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention
Atherosclerosis
Carotid Artery Disease
Procedure: Carotid endarterectomy

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Morphological and Serological Criteria of Plaque Vulnerability: Risk Assessment for Symptomatic and Asymptomatic Carotid Artery Stenosis

Resource links provided by NLM:


Further study details as provided by Wilhelminenspital Vienna:

Primary Outcome Measures:
  • 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, ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    enzyme-linked immunosorbent assay (ELISA) will be done for the determination of PEDF, VEGF, HIF-1 alpha, before and after surgery


Other Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

whole blood serum carotid artery plaque


Estimated Enrollment: 400
Study Start Date: September 2012
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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.
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02124928

Contacts
Contact: Afshin Assadian, Prim PD Dr +43 1 49150 ext 4101 afshin.assadian@wienkav.at
Contact: Jelena Basic, Dr +43 1 49150 ext 4101 jelenazbasic@gmail.com

Locations
Austria
Surgery Departement, Georg Hagmüller Institute for Vascular Research Wilheminenspital Recruiting
Vienna, Austria, 1160
Contact: Afshin Assadian, Prim PD Dr    +43 1 49150 ext 4101    afshin.assadian@wienkav.at   
Contact: Jelena Basic, Dr    +43 1 49150 ext 4101    jelenazbasic@gmail.com   
Principal Investigator: Afshin Assadian, Prim PD Dr         
Sponsors and Collaborators
Prim PD Dr Afshin Assadian
Wilhelminenspital Vienna
Investigators
Principal Investigator: Afshin Assadian, Prim PD Dr Georg Hagmüller Institute for Vascular Research Wilheminenspital Vienna, Austria
  More Information

No publications provided

Responsible Party: Prim PD Dr Afshin Assadian, Prim PD Dr, Wilhelminenspital Vienna
ClinicalTrials.gov Identifier: NCT02124928     History of Changes
Other Study ID Numbers: VUCAP, EK-11-208-VK
Study First Received: April 16, 2014
Last Updated: April 24, 2014
Health Authority: Austria: Ethikkommission

Keywords provided by Wilhelminenspital Vienna:
stroke
biomarkers
vulnerable plaque
carotid endarterectomy
carotid artery disease

Additional relevant MeSH terms:
Atherosclerosis
Carotid Artery Diseases
Carotid Stenosis
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases

ClinicalTrials.gov processed this record on July 29, 2014