Structural Stability of Carotid Plaque and Symptomatology
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|ClinicalTrials.gov Identifier: NCT02476396|
Recruitment Status : Recruiting
First Posted : June 19, 2015
Last Update Posted : December 17, 2020
|Condition or disease||Intervention/treatment|
|Carotid Stenosis Stroke Carotid Artery Plaque Transient Ischemic Attack Cerebrovascular Accident Carotid Artery Stenosis||Procedure: Carotid Endarterectomy|
|Study Type :||Observational|
|Estimated Enrollment :||244 participants|
|Official Title:||Structural Stability of Carotid Plaque and Symptomatology|
|Actual Study Start Date :||November 9, 2015|
|Estimated Primary Completion Date :||December 2022|
|Estimated Study Completion Date :||December 2022|
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 or NASCET criteria (carotid artery stenosis of 60% or greater without clinical symptoms; stenosis 70% or greater with clinical symptoms).
Procedure: Carotid Endarterectomy
Carotid endarterectomy is a procedure to treat carotid artery disease. This disease occurs when fatty, waxy deposits build up in one of the carotid arteries. The carotid arteries are blood vessels located on each side of your neck (carotid arteries).
This buildup of plaques (atherosclerosis) may restrict blood flow to your brain. Removing plaques causing the narrowing in the artery can improve blood flow in your carotid artery and reduce your risk of stroke.
In carotid endarterectomy, you an anesthetic. Your surgeon makes an incision along the front of your neck, opens your carotid artery and removes the plaques that are clogging your artery. Your surgeon then repairs the artery with stitches or a patch made with a vein or artificial material (patch graft).
Source: Mayo Clinic
The controls will be recruited by the patient-subjects. The investigators will ask their 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.
- Change in Ultrasound Strain Measurements (Gray Scale Median Value) on Carotid Plaques [ Time Frame: baseline (pre-surgery), 1 year follow up ]Ultrasound Radio frequency (RF) data will be acquired on patients, using both one-dimensional (1D) and two-dimensional (2D) wobbler and/or matrix array transducers to obtain four-dimensional (3D + time) RF data sets. The hypothesis is that plaques which have a lower gray scale median value and which during deformations of the cardiac cycles show larger stress concentrations in these regions are more vulnerable to rupture.
- Change in In-vivo velocity measured by Transcranial Doppler (TCD) [ Time Frame: baseline (pre-surgery), 1 year follow up ]TCD will be utilized to acquire in-vivo velocity (peak systolic, mean, and end diastolic velocity information) measurements of blood flow in the right and left middle cerebral arteries.
- Change in Systolic to diastolic ratio measured by transcranial Doppler (TCD) [ Time Frame: baseline (pre-surgery), 1 year follow up ]TCD will be utilized to acquire systolic to diastolic (S/D) ratio of blood flow in the right and left middle cerebral arteries.
- Change in Pulsatility index measured by transcranial Doppler (TCD) [ Time Frame: baseline (pre-surgery), 1 year follow up ]TCD will be utilized to acquire pulsatility index (PI) measurements of blood flow in the right and left middle cerebral arteries.
- Change in Resistive index measured by transcranial Doppler (TCD) [ Time Frame: baseline (pre-surgery), 1 year follow up ]TCD will be utilized to acquire resistive index (RI) measurements of blood flow in the right and left middle cerebral arteries.
- Histopathologic classification of carotid atherosclerotic plaque after removal for plaque ulceration [ Time Frame: obtained day of surgery ]Histologic classification of plaques is made using the updated classification of atherosclerotic plaques recommended by the American Heart association.
- Change in Impairment Index - General Cognitive Morbidity [ Time Frame: baseline (pre-surgery), 1 year follow up ]General cognitive morbidity will be derived by comparison of the Kaufman 4-subtest IQ and NART. The NART is brief standardized test that assesses an individual's ability to read irregular words (e.g., subtle). Performance on this test has been shown to be highly correlated with years of formal education and premorbid intellectual ability as assessed by traditional intelligence tests. Performance on NART will serve as a comparison against which to compare current IQ as determined by a brief 4-subtest version of the WAIS-R. This abbreviated IQ measure has been demonstrated to have very high correlation (r > .95) with the complete standard WAIS-R Full Scale IQ. Comparison of predicted versus obtained IQ will provide a measure of potential cognitive decline to be used in comparison of groups at study entry.
- Change in Impairment Index - Number of Abnormal Test Scores [ Time Frame: baseline (pre-surgery), 1 year follow up ]The 60-minute cognitive screen is the most thorough assessment with the greatest sensitivity to detect the cognitive disruption associated with vascular cognitive impairment (VCI). The cognitive domains to be assessed include executive function and activation, visuospatial ability, language/lexical retrieval, and memory/learning, for a total of 10 tests. A summary impairment index will be derived for each participant and include the proportion of abnormal test scores.
- Change in Impairment Index - Cognitive Domain Z-scores [ Time Frame: baseline (pre-surgery), 1 year follow up ]A summary impairment index will be derived for each participant in part using composite cognitive domain z-scores (executive function, visuospatial, language, memory).
- Thickness of the fibrous cap [ Time Frame: obtained day of surgery ]Examination of fibrous cap of the atherosclerotic plaque to measure thickness.
- Number of vascular channels [ Time Frame: obtained day of surgery ]Histopathologic examination of vascular channels to determine the number of channels in the fibrous cap vs the plaque proper.
- Percent diameter stenosis measured with MRI [ Time Frame: baseline (pre-surgery) ]The percent diameter stenosis will be determined with NASCET criteria.
- Maximum Plaque Thickness measured with MRI [ Time Frame: baseline (pre-surgery) ]Maximum plaque thickness was measured in the transverse plane, perpendicular to the center axis of the lumen
- Number of ulcerations measured with MRI [ Time Frame: baseline (pre-surgery) ]Ulceration will be determined by using a size threshold of 1 mm
- Intraluminal Thrombus measured with MRI [ Time Frame: baseline (pre-surgery) ]Intraluminal thrombus will be determined by a central filling defect
- Thinnest area of the enhancing FC [ Time Frame: baseline (pre-surgery) ]The thinnest area of the enhancing FC will be recorded with FC fissuring being defined as full thickness defects
- Carotid intraplaque hemorrhage (IPH) [ Time Frame: baseline (pre-surgery) ]Carotid IPH will be defined by MPnRAGE-positive plaque with ≥2-fold signal compared with the sternocleidomastoid muscle
- Volumetrics [ Time Frame: baseline (pre-surgery) ]Total volumes of plaque, lipid-rich necrotic core (LRNC), IPH, and neovascularity will be determined quantitatively with volumes manually segmented from multi-contrast scans
- White Matter Hyperintensity (WMH) Volumes [ Time Frame: baseline (pre-surgery) ]From brain MRI scans, WMH volume will be evaluated using semi-automated segmentation of T2-FLAIR images.
- Hemoglobin A1C [ Time Frame: baseline ]
- High-sensitivity C-reactive protein (hs-CRP) [ Time Frame: baseline ]
- Fasting Lipid Panel [ Time Frame: baseline ]
- Compare DNA between blood, plaque, and genes [ Time Frame: baseline ]
Biospecimen Retention: Samples With DNA
Subjects and controls will have 2 tubes of blood drawn. DNA will be removed and may be saved for future testing. Some cells from the participant's blood may be kept alive and growing in the laboratory as a "cell line". Creating a cell line will allow the investigators to get more DNA for future research.
Subjects will have their carotid plaques removed via standard carotid endarterectomy. This surgical procedure is part of the standard clinical care.
Blood samples will be decoded and unidentifiable, kept in a secure freezer box (with a lock and key) and stored in chamber of 1 -800C freezer used only to store human blood and RNA samples.
Plaque specimens will be de-identified. Samples will be kept in a secure freezer box stored in a chamber with authorized access only.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02476396
|Contact: Robert J Dempsey, MDemail@example.com|
|Contact: Stephanie M Wilbrand, PhDfirstname.lastname@example.org|
|United States, Wisconsin|
|University of Wisconsin-Madison||Recruiting|
|Madison, Wisconsin, United States, 53715|
|Principal Investigator:||Robert J Dempsey, MD||University of Wisconsin, Madison|