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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
Sponsor:
Collaborators:
National Heart, Lung, and Blood Institute (NHLBI)
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment
Carotid Stenosis Stroke Carotid Artery Plaque Transient Ischemic Attack Cerebrovascular Accident Carotid Artery Stenosis Procedure: Carotid Endarterectomy

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Study Type : Observational
Estimated Enrollment : 244 participants
Observational Model: Case-Control
Time Perspective: Prospective
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

Group/Cohort Intervention/treatment
patient-subject
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


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.



Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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).


Other Outcome Measures:
  1. Thickness of the fibrous cap [ Time Frame: obtained day of surgery ]
    Examination of fibrous cap of the atherosclerotic plaque to measure thickness.

  2. 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.

  3. Percent diameter stenosis measured with MRI [ Time Frame: baseline (pre-surgery) ]
    The percent diameter stenosis will be determined with NASCET criteria.

  4. 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

  5. Number of ulcerations measured with MRI [ Time Frame: baseline (pre-surgery) ]
    Ulceration will be determined by using a size threshold of 1 mm

  6. Intraluminal Thrombus measured with MRI [ Time Frame: baseline (pre-surgery) ]
    Intraluminal thrombus will be determined by a central filling defect

  7. 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

  8. 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

  9. 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

  10. 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.

  11. Hemoglobin A1C [ Time Frame: baseline ]
  12. High-sensitivity C-reactive protein (hs-CRP) [ Time Frame: baseline ]
  13. Fasting Lipid Panel [ Time Frame: baseline ]
  14. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
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).
Criteria

Inclusion Criteria (Patients):

  • Patients undergoing carotid endarterectomy for established clinical criteria
  • Age > 18 years
  • Male or Female
  • English speaking
  • Patients must sign written informed consent form

Inclusion Criteria (Controls):

  • 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 (Patients):

  • 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
  • Contraindication to MRI scans (impaired renal function, need for sedative medication during scans, inability to lie in scanner for 60 minutes)
  • Prisoner status

Exclusion Criteria (Controls):

  • Control-Subjects with impaired consent capacity
  • Prisoner status
  • Previous history of Stroke or TIAs
  • Previous history of carotid artery surgery (endovascular or open)

Information from the National Library of Medicine

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


Contacts
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Contact: Robert J Dempsey, MD 608-265-5967 dempsey@neurosurgery.wisc.edu
Contact: Stephanie M Wilbrand, PhD 608-265-9248 s.wilbrand@neurosurgery.wisc.edu

Locations
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United States, Wisconsin
University of Wisconsin-Madison Recruiting
Madison, Wisconsin, United States, 53715
Sponsors and Collaborators
University of Wisconsin, Madison
National Heart, Lung, and Blood Institute (NHLBI)
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
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Principal Investigator: Robert J Dempsey, MD University of Wisconsin, Madison
Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: University of Wisconsin, Madison
ClinicalTrials.gov Identifier: NCT02476396    
Other Study ID Numbers: 2015-0289
A535700 ( Other Identifier: UW Madison )
SMPH\NEURO SURG\NEURO SURG ( Other Identifier: UW Madison )
1F31HL141008-01A1 ( U.S. NIH Grant/Contract )
1R01HL147866-01A1 ( U.S. NIH Grant/Contract )
R01NS064034 ( U.S. NIH Grant/Contract )
Protocol Version Nov 2020 ( Other Identifier: UW Madison )
First Posted: June 19, 2015    Key Record Dates
Last Update Posted: December 17, 2020
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Additional relevant MeSH terms:
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Stroke
Ischemic Attack, Transient
Carotid Stenosis
Constriction, Pathologic
Pathological Conditions, Anatomical
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Brain Ischemia
Carotid Artery Diseases
Arterial Occlusive Diseases