AtherosclerosisVUCAPNCT02124928
Morphological and Serological Criteria of Plaque Vulnerability: Risk Assessment for Symptomatic and Asymptomatic Carotid Artery Stenosis
An observational study of Atherosclerosis and Carotid Artery Disease, run by Prim PD Dr Afshin Assadian at 1 site in Austria.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Atherosclerosis, Carotid Artery Disease
- What is being tested?
- Carotid endarterectomy
- Type of treatment
- Surgery or procedure
- How many people
- 400 participants
- Where
- 1 siteAustria
- Study dates
- Sep 2012to Dec 2017
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- asymptomatic stenosis of internal carotid artery >70%
- symptomatic stenosis of internal carotid artery >60%
- planed surgical treatment of the stenosis
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Austria1 site, 1 recruiting
- Recruiting
Surgery Departement, Georg Hagmüller Institute for Vascular Research Wilheminenspital
Vienna, 1160
Afshin Assadian, Prim PD Dr, +43 1 49150 ext. 4101, afshin.assadian@wienkav.at
Jelena Basic, Dr, +43 1 49150 ext. 4101, jelenazbasic@gmail.com
About this study
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.
Read the 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.
- Conditions
- Atherosclerosis, Carotid Artery Disease
- Being tested
- Carotid endarterectomy
- Keywords
- stroke, biomarkers, vulnerable plaque, carotid endarterectomy, carotid artery disease
- Medical subject headings
- Atherosclerosis, Carotid Artery Diseases, Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Carotid endarterectomyProcedure or surgery
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 group | Role | What they receive |
|---|---|---|
| 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. Receives: Procedure: Carotid endarterectomy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
enzyme-linked immunosorbent assay (ELISA) will be done for the determination of PEDF, VEGF, HIF-1 alpha, before and after surgery
Measured: serum blood levels are evaluated from the whole blood twice: on the day of surgery and 6 weeks after removal of the plaque
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2014 (estimated)
- Study startSep 2012
- Primary completionDec 2017 (estimated)
- Study completionDec 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AtherosclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Prim PD Dr Afshin Assadian
- Sponsor type
- University, hospital or other
- Collaborators
- Wilhelminenspital Vienna
- Responsible party
- Sponsor-investigator, Prim PD Dr Afshin Assadian, Wilhelminenspital Vienna
- Investigators
- Afshin Assadian, Prim PD Dr, Principal investigator, Georg Hagmüller Institute for Vascular Research Wilheminenspital Vienna, Austria
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02124928
- Sponsor's protocol ID
- VUCAP
- Other IDs
- EK-11-208-VK
- Acronym
- VUCAP
- Status last verified
- Sep 2015
- First submitted
- 16 Apr 2014
- Last updated
- 21 Sep 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Morphological and Serological Criteria of Plaque Vulnerability: Risk Assessment for Symptomatic and Asymptomatic Carotid Artery Stenosis
- ClinicalTrials.gov ID
- NCT02124928
- Acronym / sponsor ID
- VUCAP / VUCAP
- Conditions
- Atherosclerosis, Carotid Artery Disease
- Keywords
- stroke, biomarkers, vulnerable plaque, carotid endarterectomy, carotid artery disease
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 400 participants (estimated)
- Lead sponsor
- Prim PD Dr Afshin AssadianUniversity, hospital or other
- Collaborators
- Wilhelminenspital Vienna
- Study start
- Sep 2012
- Primary completion
- Dec 2017 (estimated)
- Study completion
- Dec 2017 (estimated)
- First posted
- 28 Apr 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| carotid artery stenosis | – | Procedure: Carotid endarterectomyPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (3 listed)
- asymptomatic stenosis of internal carotid artery >70%
- symptomatic stenosis of internal carotid artery >60%
- planed surgical treatment of the stenosis
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Carotid endarterectomyCarotid 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. | Procedure or surgery | carotid artery stenosis |
Primary outcome
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.
1 secondary outcome
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Afshin Assadian, Prim PD Dr principal investigator
Georg Hagmüller Institute for Vascular Research Wilheminenspital Vienna, Austria
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Atherosclerosis and Carotid Artery Disease, run by Prim PD Dr Afshin Assadian at 1 site in Austria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 21 Sep 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Afshin Assadian, Prim PD Dr (+43 1 49150 ext. 4101, afshin.assadian@wienkav.at), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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,). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2015.