Structural Stability of Carotid Plaque and Symptomatology

NCT02476396 | Completed

• 7 other identifiers: 2015-0289A535700SMPH\NEURO SURG\NEURO SURG1F31HL141008-01A11R01HL147866-01A1R01NS064034Protocol Version Aug 2023
• Study Type: observational
• Target: 176
• Locations: 1 country
• Sites: 1

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.

Conditions

Carotid Stenosis; Stroke; Carotid Artery Plaque; Transient Ischemic Attack; Cerebrovascular Accident; Carotid Artery Stenosis

Outcome Measures

Primary Outcomes (7)

• Change in Ultrasound Strain Measurements (Gray Scale Median Value) on Carotid Plaques

  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.

  baseline (pre-surgery), 1 year follow up

• Change in In-vivo velocity measured by Transcranial Doppler (TCD)

  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.

  baseline (pre-surgery), 1 year follow up

• Change in Systolic to diastolic ratio measured by transcranial Doppler (TCD)

  TCD will be utilized to acquire systolic to diastolic (S/D) ratio of blood flow in the right and left middle cerebral arteries.

  baseline (pre-surgery), 1 year follow up

• Change in Pulsatility index measured by transcranial Doppler (TCD)

  TCD will be utilized to acquire pulsatility index (PI) measurements of blood flow in the right and left middle cerebral arteries.

  baseline (pre-surgery), 1 year follow up

• Change in Resistive index measured by transcranial Doppler (TCD)

  TCD will be utilized to acquire resistive index (RI) measurements of blood flow in the right and left middle cerebral arteries.

  baseline (pre-surgery), 1 year follow up

• Histopathologic classification of carotid atherosclerotic plaque after removal for plaque ulceration

  Histologic classification of plaques is made using the updated classification of atherosclerotic plaques recommended by the American Heart association.

  obtained day of surgery

• Change in Impairment Index - General Cognitive Morbidity

  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.

  baseline (pre-surgery), 1 year follow up

Secondary Outcomes (2)

• Change in Impairment Index - Number of Abnormal Test Scores

  baseline (pre-surgery), 1 year follow up

• Change in Impairment Index - Cognitive Domain Z-scores

  baseline (pre-surgery), 1 year follow up

Other Outcomes (14)

• Thickness of the fibrous cap

  obtained day of surgery

• Number of vascular channels

  obtained day of surgery

• Percent diameter stenosis measured with MRI

  baseline (pre-surgery)

Study Arms (2)

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).

Procedure: Carotid Endarterectomy or Stenting

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.

Interventions

Carotid Endarterectomy or Stenting PROCEDURE

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-subject

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients will be recruited from the population of patients scheduled to undergo carotid endarterectomy or stenting 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).

You may qualify if:

• Patients undergoing carotid endarterectomy or stenting (endovascular) for established clinical 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

You may not qualify if:

• Previous history of carotid artery surgery (endovascular or open) on the same side
• 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)

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• University of Wisconsin, Madison: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

University of Wisconsin-Madison

Madison, Wisconsin, 53715, United States

Location

Related Publications (15)

• 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.

  PMID: 25571271 BACKGROUND

• 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.

  PMID: 24120415 BACKGROUND

• 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.

  PMID: 23246924 BACKGROUND

• 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.

  PMID: 23079725 BACKGROUND

• 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.

  PMID: 22658531 BACKGROUND

• 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.

  PMID: 20644437 BACKGROUND

• 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.

  PMID: 19640556 BACKGROUND

• 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.

  PMID: 18490099 BACKGROUND

• 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.

  PMID: 17491296 BACKGROUND

• 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.

  PMID: 16639334 BACKGROUND

• 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.

  PMID: 16635256 BACKGROUND

• 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.

  PMID: 15708479 BACKGROUND

• 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.

  PMID: 18941278 BACKGROUND

• 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.

  PMID: 28298048 DERIVED

• 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.

  PMID: 27720278 DERIVED

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.

MeSH Terms

Conditions

Carotid Stenosis; Stroke; Ischemic Attack, Transient

Interventions

Endarterectomy, Carotid; Stents

Condition Hierarchy (Ancestors)

Carotid Artery Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Brain Ischemia

Intervention Hierarchy (Ancestors)

Endarterectomy; Vascular Surgical Procedures; Cardiovascular Surgical Procedures; Surgical Procedures, Operative; Prostheses and Implants; Equipment and Supplies

Study Officials

• Robert J Dempsey, MD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 5, 2015
• First Posted: June 19, 2015
• Study Start: November 9, 2015
• Primary Completion: July 14, 2024
• Study Completion: July 14, 2024
• Last Updated: August 16, 2024

Record last verified: 2024-08

Locations

US (1)