Structural Stability of Carotid Plaque and Symptomatology
NCT ID: NCT02476396
Last Updated: 2024-08-16
Study Results
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Basic Information
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COMPLETED
176 participants
OBSERVATIONAL
2015-11-09
2024-07-14
Brief Summary
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Detailed Description
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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.
Conditions
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Study Design
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CASE_CONTROL
PROSPECTIVE
Study Groups
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patient-subject
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).
Carotid Endarterectomy or Stenting
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
Carotid stenting uses a expandable metal coil to prevent the artery from narrowing.
patient-control
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.
No interventions assigned to this group
Interventions
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Carotid Endarterectomy or Stenting
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
Carotid stenting uses a expandable metal coil to prevent the artery from narrowing.
Eligibility Criteria
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Inclusion Criteria
* Age \> 18 years
* Male or Female
* English speaking
* Patients must sign written informed consent form
* A spouse or sibling of a Patient Subject
* Age \> 18 years
* Male or Female
* English speaking
* Control-Subject must sign a written informed consent form
Exclusion Criteria
* Previous cervical radiation
* Patients not felt be suitable for carotid endarterectomy or stenting (endovascular)
* Patients with impaired consent capacity
* Contraindication to MRI scans (impaired renal function, need for sedative medication during scans, inability to lie in scanner for 60 minutes)
* Prisoner status
* Control-Subjects with impaired consent capacity
* Prisoner status
* Previous history of Stroke or TIAs
* Previous history of carotid artery surgery (endovascular or open)
18 Years
ALL
No
Sponsors
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National Heart, Lung, and Blood Institute (NHLBI)
NIH
National Institute of Neurological Disorders and Stroke (NINDS)
NIH
University of Wisconsin, Madison
OTHER
Responsible Party
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Principal Investigators
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Robert J Dempsey, MD
Role: PRINCIPAL_INVESTIGATOR
University of Wisconsin, Madison
Locations
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University of Wisconsin-Madison
Madison, Wisconsin, United States
Countries
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References
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Wang X, Jackson DC, Mitchell CC, Varghese T, Hermann BP, Kliewer MA, Dempsey RJ. Estimation of ultrasound strain indices in carotid plaque and correlation to cognitive dysfunction. Annu Int Conf IEEE Eng Med Biol Soc. 2014;2014:5627-30. doi: 10.1109/EMBC.2014.6944903.
Wang X, Jackson DC, Varghese T, Mitchell CC, Hermann BP, Kliewer MA, Dempsey RJ. Correlation of cognitive function with ultrasound strain indices in carotid plaque. Ultrasound Med Biol. 2014 Jan;40(1):78-89. doi: 10.1016/j.ultrasmedbio.2013.08.001. Epub 2013 Oct 11.
Wesley UV, Vemuganti R, Ayvaci ER, Dempsey RJ. Galectin-3 enhances angiogenic and migratory potential of microglial cells via modulation of integrin linked kinase signaling. Brain Res. 2013 Feb 16;1496:1-9. doi: 10.1016/j.brainres.2012.12.008. Epub 2012 Dec 14.
McCormick M, Varghese T, Wang X, Mitchell C, Kliewer MA, Dempsey RJ. Methods for robust in vivo strain estimation in the carotid artery. Phys Med Biol. 2012 Nov 21;57(22):7329-53. doi: 10.1088/0031-9155/57/22/7329. Epub 2012 Oct 18.
Rocque BG, Jackson D, Varghese T, Hermann B, McCormick M, Kliewer M, Mitchell C, Dempsey RJ. Impaired cognitive function in patients with atherosclerotic carotid stenosis and correlation with ultrasound strain measurements. J Neurol Sci. 2012 Nov 15;322(1-2):20-4. doi: 10.1016/j.jns.2012.05.020. Epub 2012 Jun 1.
Dempsey RJ, Vemuganti R, Varghese T, Hermann BP. A review of carotid atherosclerosis and vascular cognitive decline: a new understanding of the keys to symptomology. Neurosurgery. 2010 Aug;67(2):484-93; discussion 493-4. doi: 10.1227/01.NEU.0000371730.11404.36.
Shi H, Varghese T, Mitchell CC, McCormick M, Dempsey RJ, Kliewer MA. In vivo attenuation and equivalent scatterer size parameters for atherosclerotic carotid plaque: preliminary results. Ultrasonics. 2009 Dec;49(8):779-85. doi: 10.1016/j.ultras.2009.06.004. Epub 2009 Jul 3.
Shi H, Varghese T, Dempsey RJ, Salamat MS, Zagzebski JA. Relationship between ultrasonic attenuation, size and axial strain parameters for ex vivo atherosclerotic carotid plaque. Ultrasound Med Biol. 2008 Oct;34(10):1666-77. doi: 10.1016/j.ultrasmedbio.2008.02.014. Epub 2008 May 19.
Shi H, Tu H, Dempsey RJ, Varghese T. Ultrasonic attenuation estimation in small plaque samples using a power difference method. Ultrason Imaging. 2007 Jan;29(1):15-30. doi: 10.1177/016173460702900102.
Tureyen K, Vemuganti R, Salamat MS, Dempsey RJ. Increased angiogenesis and angiogenic gene expression in carotid artery plaques from symptomatic stroke patients. Neurosurgery. 2006 May;58(5):971-7; discussion 971-7. doi: 10.1227/01.NEU.0000210246.61817.FE.
Vemuganti R, Dempsey RJ. Increased expression of genes that control ionic homeostasis, second messenger signaling and metabolism in the carotid plaques from patients with symptomatic stroke. J Neurochem. 2006 Apr;97 Suppl 1:92-6. doi: 10.1111/j.1471-4159.2005.03516.x.
Vemuganti R, Dempsey RJ. Carotid atherosclerotic plaques from symptomatic stroke patients share the molecular fingerprints to develop in a neoplastic fashion: a microarray analysis study. Neuroscience. 2005;131(2):359-74. doi: 10.1016/j.neuroscience.2004.08.058.
Shi H, Mitchell CC, McCormick M, Kliewer MA, Dempsey RJ, Varghese T. Preliminary in vivo atherosclerotic carotid plaque characterization using the accumulated axial strain and relative lateral shift strain indices. Phys Med Biol. 2008 Nov 21;53(22):6377-94. doi: 10.1088/0031-9155/53/22/008. Epub 2008 Oct 21.
Dempsey RJ, Varghese T, Jackson DC, Wang X, Meshram NH, Mitchell CC, Hermann BP, Johnson SC, Berman SE, Wilbrand SM. Carotid atherosclerotic plaque instability and cognition determined by ultrasound-measured plaque strain in asymptomatic patients with significant stenosis. J Neurosurg. 2018 Jan;128(1):111-119. doi: 10.3171/2016.10.JNS161299. Epub 2017 Mar 10.
Mitchell CC, Stein JH, Cook TD, Salamat S, Wang X, Varghese T, Jackson DC, Sandoval Garcia C, Wilbrand SM, Dempsey RJ. Histopathologic Validation of Grayscale Carotid Plaque Characteristics Related to Plaque Vulnerability. Ultrasound Med Biol. 2017 Jan;43(1):129-137. doi: 10.1016/j.ultrasmedbio.2016.08.011. Epub 2016 Oct 5.
Other Identifiers
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A535700
Identifier Type: OTHER
Identifier Source: secondary_id
SMPH\NEURO SURG\NEURO SURG
Identifier Type: OTHER
Identifier Source: secondary_id
Protocol Version Aug 2023
Identifier Type: OTHER
Identifier Source: secondary_id
2015-0289
Identifier Type: -
Identifier Source: org_study_id
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