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

NCT02124928 | Unknown

• 2 other identifiers: VUCAPEK-11-208-VK
• Study Type: observational
• Target: 400
• Locations: 1 country
• Sites: 1

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.

Conditions

Atherosclerosis; Carotid Artery Disease

Keywords

stroke; biomarkers; vulnerable plaque; carotid endarterectomy; carotid artery disease

Outcome Measures

Primary Outcomes (1)

• 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)

  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.

  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,

Secondary Outcomes (1)

• 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

  serum blood levels are evaluated from the whole blood twice: on the day of surgery and 6 weeks after removal of the plaque

Other Outcomes (1)

• composite end point of death, stroke, myocardial infarction

  From date of randomization until the date of first documented or date of death from any cause assessed up to 5 years

Study Arms (1)

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

Interventions

Carotid endarterectomy PROCEDURE

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.

carotid artery stenosis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Prim PD Dr Afshin Assadian: lead
• Wilhelminenspital Vienna: collaborator

Study Sites (1)

Surgery Departement, Georg Hagmüller Institute for Vascular Research Wilheminenspital

Vienna, 1160, Austria

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

whole blood serum carotid artery plaque

MeSH Terms

Conditions

Atherosclerosis; Carotid Artery Diseases; Stroke

Interventions

Endarterectomy, Carotid

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Endarterectomy; Vascular Surgical Procedures; Cardiovascular Surgical Procedures; Surgical Procedures, Operative

Study Officials

• Afshin Assadian, Prim PD Dr

  Georg Hagmüller Institute for Vascular Research Wilheminenspital Vienna, Austria

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Afshin Assadian, Prim PD Dr

CONTACT

+43 1 49150; afshin.assadian@wienkav.at

Jelena Basic, Dr

CONTACT

+43 1 49150; jelenazbasic@gmail.com

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prim PD Dr

Study Record Dates

• First Submitted: April 16, 2014
• First Posted: April 28, 2014
• Study Start: September 1, 2012
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: September 21, 2015

Record last verified: 2015-09

Locations

AU (1)