Structural Stability of Carotid Plaque and Symptomatology
- Conditions
- StrokeCarotid Artery PlaqueCerebrovascular AccidentCarotid StenosisTransient Ischemic AttackCarotid Artery Stenosis
- Interventions
- Procedure: Carotid Endarterectomy or Stenting
- Registration Number
- NCT02476396
- Lead Sponsor
- University of Wisconsin, Madison
- Brief Summary
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.
- Detailed Description
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. Current treatments for carotid artery stenosis include either carotid endarterectomy to remove plaque or carotid stenting using a expandable metal coil to prevent the artery from narrowing.
In the previous version of this protocol, the investigators have enrolled 95 -subjects (75 patient-subjects and 20 control-subjects) with no safety concerns. Findings include new understanding of the relatively of atherosclerosis and cognition as well as the basic pathophysiology of atherosclerotic large to small vessel disease.
The study will run for 5 years from IRB approval with potential to further expand it. All patient-subjects will have a baseline and 1-year follow-up, ultrasound, TCD, blood collection and cognitive study to see if endarterectomy or stenting (endovascular) affected pre-op change. Change in cognition will be compared to report studies in the normal control group. In past, carotid patients have been recruited 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, and histopathology and 1-year follow-up the patient received in the last year of recruitment will take place. The 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.
* Specific Aim 1: Atherosclerosis, plaque elasticity, strain defects and histopathology of plaque. This aim will study the relationship of structural instability in the carotid plaques with histopathologic evidence for fissuring of the plaques that may represent a micro-emboli source. The determination of a structural defect causing abnormal strain measurements in a carotid atherosclerotic plaque will be important in understanding the pathophysiology of this disorder, as well as, addressing future treatment strategies, which could include preventing angiogenesis, thrombosis, or abnormal cholesterol deposit within the plaque.
* Specific Aim 2: Plaque strain deficits and microemboli. In this aim, the investigators will preoperatively measure the structural stability of each plaque ultrasonically while simultaneously recording distally for the presence of microemboli over time within the carotid system. Statistical analysis will establish the structural instability signature that predicts ongoing subclinical microemboli.
* Specific Aim 3: Plaque strain deficits, microemboli, and cognition. This aim will analyze increased elasticity strain within carotid plaques as measured preoperatively with ultrasound and correlate these parameters with cognition
* Specific Aim 4: Blood RNA expression profiles can be used as biomarkers to identify the patients with a higher risk of plaque instability. This aim will analyze the mRNA and microRNA expression profiles of the blood and the excised plaque samples from patients with stable and ruptured carotid atherosclerotic plaques. The RNA analysis will be conducted with the microarrays.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 176
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description patient-subject Carotid Endarterectomy or Stenting Patients will be recruited from the population of patients scheduled to undergo carotid endarterectomy or stenting (endovascular) for established clinical indications. These indications include patients scheduled to have a carotid endarterectomy or stenting 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).
- Primary Outcome Measures
Name Time Method Change in Ultrasound Strain Measurements (Gray Scale Median Value) on Carotid Plaques 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 Systolic to diastolic ratio measured by transcranial Doppler (TCD) 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 Resistive index measured by transcranial Doppler (TCD) 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 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 In-vivo velocity measured by Transcranial Doppler (TCD) 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 Pulsatility index measured by transcranial Doppler (TCD) 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 Impairment Index - General Cognitive Morbidity 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.
- Secondary Outcome Measures
Name Time Method Change in Impairment Index - Number of Abnormal Test Scores 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 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).
Trial Locations
- Locations (1)
University of Wisconsin-Madison
🇺🇸Madison, Wisconsin, United States