Madison, Wisconsin 53715


Purpose:

The purpose of the research is to understand structural plaque abnormalities that make a carotid plaque unstable and brake off (embolize) which would help to predict and treat individuals who are likely to suffer not only classic episodic major strokes but also cognitive impairment.


Study summary:

This study examines the relationship between the structural stability of carotid atherosclerotic plaque forming at the bifurcation of the common internal/external carotids and the ability of such lesions to cause disease. The theory behind this work is the hypothesis that carotid atherosclerotic stroke presents not only as a classical episodic clinical condition, but may also involve elements of a continuous process involving large and small vessel circulations, microcirculatory changes, cellular metabolic resistance to ischemia and micro embolic events. Recent studies suggest for every recognized clinical stroke, 5 silent strokes take place. The patient implications are enormous as imaging suggests 11 million "silent strokes" occur yearly in the US with poor understanding of the pathophysiology or cognitive consequences for our patients. Within this framework, the investigators choose to study the hypothesis that carotid artery atherosclerosis is likely to cause microemboli, as well as classic macroemboli, which may result in more subtle disturbances than those ordinarily detected by more obvious clinical events such as stroke and transient ischemia attacks. Understanding the structural plaque abnormalities that render a carotid plaque unstable and at risk of embolization would help to predict and treat individuals who are likely to suffer not only classic episodic major strokes, but also cognitive impairment from the contribution of microemboli to this overall disease process. The investigators have previously described a non-invasive ultrasound based measure of plaque structural stability which will be further studied in this proposal. This study will expand on previous work performed at the University of Wisconsin-Madison, and will include patients with carotid artery stenosis, both with and without classic stroke symptoms, as well as a control group of patients without known atherosclerotic disease. Patients will be recruited from the population of patients scheduled to undergo carotid endarterectomy for established clinical indications. These indications include patients scheduled to have a carotid endarterectomy due to the presence of a high-grade atherosclerotic cervical internal carotid artery stenosis with or without clinical symptoms, following the ACAS (Asymptomatic Carotid Atherosclerosis Study) or NASCET criteria (The North American Symptomatic Carotid Endarterectomy Trial) (carotid artery stenosis of 60% or greater without clinical symptoms; stenosis 70% or greater with clinical symptoms). Patients will be recruited from University of Wisconsin Hospital and Clinics Neurosurgery Clinic and inpatient units. With this renewal the investigators would like to complete previously approved sample size of 144 patient-subjects. In the previous protocol 75 patients-subjects were enrolled, remaining 69 patient-subjects to be enrolled in this study. The investigators also have previously approved enrollment for 50 control-subjects. Having enrolled 20 in the previous protocol the investigators will complete enrollment with enrolling additional 30 control-subjects These controls will be recruited by the patient-subjects. The investigators will ask the patient-subjects to speak to a spouse or family member to see if they are interested in participating. If they do have an interest they will contact the research team/study coordinator(s). In case, a spouse or a family member is accompanying the patient-subject, they will be recruited at the same time as the patient-subject. The Investigators have demonstrated by their experience of carotid endarterectomy in asymptomatic and symptomatic disease (>25 per year) and their very high recruitment rates in their pilot study (>95%) that sufficient experience exists for successful recruitment of this population over the time of the study. All patients will undergo confirmation of the degree of stenosis by standard clinical methodology including angiography, magnetic resonance imaging, computerized tomographic angiography, and/or ultrasonic determination. Patients enrolled in the study will obtain a health questionnaire highlighting atherosclerotic risk factors, history of other atherosclerotic events involving other organs, known history of hyperlipidemia, smoking, hypertension, diabetes, cardiac disorders, or family history of above. Results will be stratified according to these risk factors. All these patients will undergo preoperative neuropsychological cognitive testing, ultrasound testing of the atherosclerotic plaque for determination of elasticity and strain, as well as TCD (transcranial doppler) measurement of emboli, MRI testing for analysis of MRI predictors of cognition and ischemic vascular disease as per our preliminary studies, as well as blood collection. At the time of surgery, the atherosclerotic plaque through the carotid bifurcation will be removed in total and will be examined histopathologically at a point by point comparison with the ultrasonic strain measurements. These will be studied for gross ulceration, micro ulceration, formation of thrombus and platelet deposition, inflammatory cells and neovascularity as measured with immunostaining for the marker for microvascular endothelial presence. All studies but the histopathologic evaluation will be obtained in the immediate preoperative period and will be repeated at one year post surgery to determine if CEA (Carotid Endarterectomy) durably stabilizes vessel wall elasticity and halts microemboli on MRI and cognitive decline. The study will run for 5 years from IRB (Institutional Review Board) approval. Recruitment of subjects will take place over the first three and half years. All patient-subjects will have 1-year follow-up, MRI, ultrasound, TCD, blood collection and cognitive study to see if endarterectomy affected pre-op change. Change in cognition will be compared to report studies in the normal control group. In past, the investigators have recruited carotid patients at a greater pace. Given the complexity of these studies the investigators anticipate recruitment and complete analysis of 20 patients/year. During this time initial psychological testing will be done pre-operatively. During the final year of the study, the data analysis of the plaque ultrasounds, MRI and histopathology and 1-year follow-up the patient received in the last year of recruitment will take place. Investigators can recruit additional patients to fill any missing data points if these results identify a subset of classically asymptomatic patients with significant carotid plaques and microemboli causing vascular cognitive decline.


Criteria:

Inclusion Criteria: - Patients undergoing carotid endarterectomy for established clinical criteria - Age > 18 years - Male or Female - English speaking - Patients must sign written informed consent form Exclusion Criteria: - Previous history of carotid artery surgery (endovascular or open) - Previous cervical radiation - Patients not felt be suitable for carotid endarterectomy - Patients with impaired consent capacity - Prisoner status


NCT ID:

NCT02476396


Primary Contact:

Principal Investigator
Robert J Dempsey, MD
University of Wisconsin, Madison

Robert J Dempsey, MD
Phone: 608-265-5967
Email: dempsey@neurosurgery.wisc.edu


Backup Contact:

Email: s.wilbrand@neurosurgery.wisc.edu
Stephanie M Wilbrand, PhD
Phone: 608-265-9248


Location Contact:

Madison, Wisconsin 53715
United States



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Site Status: Recruiting


Data Source: ClinicalTrials.gov

Date Processed: November 19, 2017

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