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Transcutaneous ARFI Ultrasound for Differentiating Carotid Plaque With High Stroke Risk

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ClinicalTrials.gov Identifier: NCT04063709
Recruitment Status : Recruiting
First Posted : August 21, 2019
Last Update Posted : August 21, 2019
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill

Brief Summary:
Stroke is a leading cause of death and disability in the United States and around the world. The goal of this work is to develop and test a noninvasive ultrasound-based imaging technology to better identify patients at high risk of stroke so that appropriate and timely intervention may be administered to prevent it.

Condition or disease Intervention/treatment Phase
Plaque, Atherosclerotic Carotid Artery Plaque Carotid Stenosis Diagnostic Test: Acoustic Radiation Force Impulse (ARFI) ultrasound Not Applicable

Detailed Description:

Although stroke remains a leading cause of death in the United States, incidence and mortality rates have declined over the past two decades in association with advanced pharmaceutical therapies and revascularization, primarily by carotid endarterectomy (CEA). While CEA's efficacy for preventing stroke in patients with severe (≥70%) carotid artery stenosis and neurological symptoms is well documented, the surgical intervention's usefulness decreases as stroke risk falls in patients with less severe stenosis and patients without symptoms. It is estimated that as many as 13 out of 14 symptomatic patients with 50-69% stenosis and 21 out of 22 asymptomatic patients with 70-99% stenosis undergo CEA surgery unnecessarily. These data demonstrate the inadequacy of degree of stenosis as the primary indication of stroke risk and underscore the urgent yet unmet need for improved biomarkers that differentiate patients at low risk of embolic stroke from those in need of CEA to prevent it.

This urgent need for improving CEA indication could be met by assessing the structure and composition of carotid plaques. Plaques composed of thin or ruptured fibrous caps (TRFC), large lipid rich necrotic cores (LRNC), and intraplaque hemorrhage (IPH) are associated with thrombosis in morphological studies from autopsy. Further, plaque hemorrhage and increased intraplaque vessel formation in CEA specimens are independently related to future cardio- and cerebrovascular events or interventions. Finally, previous stroke or transient ischemic attack (TIA) is associated with TRFC and IPH - while increased risk of future stroke or TIA is conferred by TRFC, LRNC, and IPH - in human carotid plaques as determined by in vivo magnetic resonance imaging (MRI).

The goal of this work is to develop a low-cost, noninvasive imaging method that reliably delineates carotid plaque structure and composition and is suitable for widespread diagnostic application. Previous research has demonstrated that Acoustic Radiation Force Impulse (ARFI) ultrasound delineates LRNC/IPH, collagen/calcium deposits, and TRFC in human carotid plaque, in vivo, with TRFC thickness measurement as low as 0.49 mm - the mean thickness associated with rupture. This project will exploit ARFI Variance of Acceleration (VoA) imaging, higher center frequencies, and harmonic imaging to newly enable separate discrimination of TRFC, LRNC, and IPH and accurate feature size measurement. The investigators will determine the association between advanced ARFI's plaque characterization and recent history of ipsilateral stroke or TIA.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: This unblinded, open-label, exploratory study will be conducted in 60 patients with clinical indication for carotid endarterectomy (CEA). Among these 60 patients, N=20 will be symptomatic with 50-69% carotid artery stenosis, N=20 will be symptomatic with 70-99% stenosis, and N=20 will be asymptomatic with 70-99% stenosis. The study will also be conducted in N=20 additional patients without clinical indication for CEA. These patients will be asymptomatic with 50-60% stenosis.
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Transcutaneous ARFI Ultrasound for Differentiating Carotid Plaque With High Stroke Risk
Actual Study Start Date : July 17, 2019
Estimated Primary Completion Date : July 16, 2023
Estimated Study Completion Date : July 16, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Ultrasound

Arm Intervention/treatment
Experimental: Symptomatic with 50-69% stenosis
Patients 18 years of age or older who have been selected by their treating physician to be in need of carotid revascularization by CEA, with 50-69% stenotic carotid plaque with associated neurological symptoms. Acoustic Radiation Force Impulse (ARFI) ultrasound imaging will be performed on the carotid plaque.
Diagnostic Test: Acoustic Radiation Force Impulse (ARFI) ultrasound
ARFI imaging is an ultrasound-based, noninvasive imaging method and will be used in accordance with approved labeling.

Experimental: Symptomatic with 70-99% stenosis
Patients 18 years of age or older who have been selected by their treating physician to be in need of carotid revascularization by CEA, with 70-99% stenotic carotid plaque with associated neurological symptoms. ARFI ultrasound imaging will be performed on the carotid plaque.
Diagnostic Test: Acoustic Radiation Force Impulse (ARFI) ultrasound
ARFI imaging is an ultrasound-based, noninvasive imaging method and will be used in accordance with approved labeling.

Experimental: Asymptomatic with 70-99% stenosis
Patients 18 years of age or older who have been selected by their treating physician to be in need of carotid revascularization by CEA, with 70-99% stenotic carotid plaque without associated neurological symptoms. ARFI ultrasound imaging will be performed on the carotid plaque.
Diagnostic Test: Acoustic Radiation Force Impulse (ARFI) ultrasound
ARFI imaging is an ultrasound-based, noninvasive imaging method and will be used in accordance with approved labeling.

Experimental: Asymptomatic with 50-69% stenosis
Patients 18 years of age or older who have been diagnosed with 50-69% carotid artery stenosis without clinical indication for CEA.
Diagnostic Test: Acoustic Radiation Force Impulse (ARFI) ultrasound
ARFI imaging is an ultrasound-based, noninvasive imaging method and will be used in accordance with approved labeling.




Primary Outcome Measures :
  1. Acoustic Radiation Force Impulse (ARFI) imaging [ Time Frame: During the procedure ]
    Ability of ARFI imaging to detect carotid plaque features and measure their size


Secondary Outcome Measures :
  1. VoA AUC for thin or ruptured fibrous caps (TRFC) at 8 MHz fundamental [ Time Frame: During the procedure ]
    Area Under the Curve (AUC) for the ability of ARFI Variance of Acceleration (VoA) obtained at 8 MHz fundamental frequency to detect thin or ruptured fibrous cap

  2. PD AUC for TRFC at 8 MHz fundamental [ Time Frame: During the procedure ]
    AUC for the ability of ARFI PD obtained at 8 MHz fundamental frequency to detect thin or ruptured fibrous cap

  3. VoA AUC for TRFC at 12 MHz fundamental [ Time Frame: During the procedure ]
    AUC for the ability of ARFI VoA obtained at 12 MHz fundamental frequency to detect thin or ruptured fibrous cap

  4. PD AUC for TRFC at 12 MHz fundamental [ Time Frame: During the procedure ]
    AUC for the ability of ARFI PD obtained at 12 MHz fundamental frequency to detect thin or ruptured fibrous cap

  5. VoA AUC for TRFC at 12 MHz harmonic [ Time Frame: During the procedure ]
    AUC for the ability of ARFI VoA obtained at 12 MHz harmonic frequency to detect thin or ruptured fibrous cap

  6. PD AUC for TRFC at 12 MHz harmonic [ Time Frame: During the procedure ]
    AUC for the ability of ARFI PD obtained at 12 MHz harmonic frequency to detect thin or ruptured fibrous cap

  7. VoA AUC for LRNC at 8 MHz fundamental [ Time Frame: During the procedure ]
    AUC for the ability of ARFI VoA obtained at 8 MHz fundamental frequency to detect lipid rich necrotic core (LRNC)

  8. PD AUC for LRNC at 8 MHz fundamental [ Time Frame: During the procedure ]
    AUC for the ability of ARFI PD obtained at 8 MHz fundamental frequency to detect lipid rich necrotic core

  9. VoA AUC for LRNC at 12 MHz fundamental [ Time Frame: During the procedure ]
    AUC for the ability of ARFI VoA obtained at 12 MHz fundamental frequency to detect lipid rich necrotic core

  10. PD AUC for LRNC at 12 MHz fundamental [ Time Frame: During the procedure ]
    AUC for the ability of ARFI PD obtained at 12 MHz fundamental frequency to detect lipid rich necrotic core

  11. VoA AUC for LRNC at 12 MHz harmonic [ Time Frame: During the procedure ]
    AUC for the ability of ARFI VoA obtained at 12 MHz harmonic frequency to detect lipid rich necrotic core

  12. PD AUC for LRNC at 12 MHz harmonic [ Time Frame: During the procedure ]
    AUC for the ability of ARFI PD obtained at 12 MHz harmonic frequency to detect lipid rich necrotic core

  13. VoA AUC for IPH at 8 MHz fundamental [ Time Frame: During the procedure ]
    AUC for the ability of ARFI VoA obtained at 8 MHz fundamental frequency to detect intraplaque hemorrhage

  14. PD AUC for IPH at 8 MHz fundamental [ Time Frame: During the procedure ]
    AUC for the ability of ARFI PD obtained at 8 MHz fundamental frequency to detect intraplaque hemorrhage

  15. VoA AUC for IPH at 12 MHz fundamental [ Time Frame: During the procedure ]
    AUC for the ability of ARFI VoA obtained at 12 MHz fundamental frequency to detect intraplaque hemorrhage

  16. PD AUC for IPH at 12 MHz fundamental [ Time Frame: During the procedure ]
    AUC for the ability of ARFI PD obtained at 12 MHz fundamental frequency to detect intraplaque hemorrhage

  17. VoA AUC for IPH at 12 MHz harmonic [ Time Frame: During the procedure ]
    AUC for the ability of ARFI VoA obtained at 12 MHz harmonic frequency to detect intraplaque hemorrhage

  18. PD AUC for IPH at 12 MHz harmonic [ Time Frame: During the procedure ]
    AUC for the ability of ARFI PD obtained at 12 MHz harmonic frequency to detect intraplaque hemorrhage

  19. VoA bias for TRFC thickness at 8 MHz fundamental [ Time Frame: During the procedure ]
    Bland Altman-derived bias in VoA-based TRFC thickness measurement 8 MHz fundamental frequency

  20. PD bias for TRFC thickness at 8 MHz fundamental [ Time Frame: During the procedure ]
    Bland Altman-derived bias in PD-based TRFC thickness measurement 8 MHz fundamental frequency

  21. VoA bias for TRFC thickness at 12 MHz fundamental [ Time Frame: During the procedure ]
    Bland Altman-derived bias in VoA-based TRFC thickness measurement at 12 MHz fundamental frequency

  22. PD bias for TRFC thickness at 12 MHz fundamental [ Time Frame: During the procedure ]
    Bland Altman-derived bias in PD-based TRFC thickness measurement at 12 MHz fundamental frequency

  23. VoA bias for TRFC thickness at 12 MHz harmonic [ Time Frame: During the procedure ]
    Bland Altman-derived bias in VoA-based TRFC thickness measurement at 12 MHz harmonic frequency

  24. PD bias for TRFC thickness at 12 MHz harmonic [ Time Frame: During the procedure ]
    Bland Altman-derived bias in PD-based TRFC thickness measurement at 12 MHz harmonic frequency

  25. VoA bias for LRNC size at 8 MHz fundamental [ Time Frame: During the procedure ]
    Bland Altman-derived bias in VoA-based LRNC size measurement at 8 MHz fundamental frequency

  26. PD bias for LRNC size at 8 MHz fundamental [ Time Frame: During the procedure ]
    Bland Altman-derived bias in PD-based LRNC size measurement at 8 MHz fundamental frequency

  27. VoA bias for LRNC size at 12 MHz fundamental [ Time Frame: During the procedure ]
    Bland Altman-derived bias in VoA-based LRNC size measurement at 12 MHz fundamental frequency

  28. PD bias for LRNC size at 12 MHz fundamental [ Time Frame: During the procedure ]
    Bland Altman-derived bias in PD-based LRNC size measurement at 12 MHz fundamental frequency

  29. VoA bias for LRNC size at 12 MHz harmonic [ Time Frame: During the procedure ]
    Bland Altman-derived bias in VoA-based LRNC size measurement at 12 MHz harmonic frequency

  30. PD bias for LRNC size at 12 MHz harmonic [ Time Frame: During the procedure ]
    Bland Altman-derived bias in PD-based LRNC size measurement at 12 MHz harmonic frequency

  31. VoA bias for IPH size at 8 MHz fundamental [ Time Frame: During the procedure ]
    Bland Altman-derived bias in VoA-based IPH size measurement at 8 MHz fundamental frequency

  32. PD bias for IPH size at 8 MHz fundamental [ Time Frame: During the procedure ]
    Bland Altman-derived bias in PD-based IPH size measurement at 8 MHz fundamental frequency

  33. VoA bias for IPH size at 12 MHz fundamental [ Time Frame: During the procedure ]
    Bland Altman-derived bias in VoA-based IPH size measurement at 12 MHz fundamental frequency

  34. PD bias for IPH size at 12 MHz fundamental [ Time Frame: During the procedure ]
    Bland Altman-derived bias in PD-based IPH size measurement at 12 MHz fundamental frequency

  35. VoA bias for IPH size at 12 MHz harmonic [ Time Frame: During the procedure ]
    Bland Altman-derived bias in VoA-based IPH size measurement at 12 MHz harmonic frequency

  36. PD bias for IPH size at 12 MHz harmonic [ Time Frame: During the procedure ]
    Bland Altman-derived bias in PD-based IPH size measurement at 12 MHz harmonic frequency

  37. VoA prevalence of TRFC detection at 8 MHz fundamental [ Time Frame: During the procedure ]
    prevalence of reader-detected TRFC from VoA at 8 MHz fundamental frequency

  38. PD prevalence of TRFC detection at 8 MHz fundamental [ Time Frame: During the procedure ]
    prevalence of reader-detected TRFC from PD at 8 MHz fundamental frequency

  39. VoA prevalence of TRFC detection at 12 MHz fundamental [ Time Frame: During the procedure ]
    prevalence of reader-detected TRFC from VoA at 12 MHz fundamental frequency

  40. PD prevalence of TRFC detection at 12 MHz fundamental [ Time Frame: During the procedure ]
    prevalence of reader-detected TRFC from PD at 12 MHz fundamental frequency

  41. VoA prevalence of TRFC detection at 12 MHz harmonic [ Time Frame: During the procedure ]
    prevalence of reader-detected TRFC from VoA at 12 MHz harmonic frequency

  42. PD prevalence of TRFC detection at 12 MHz harmonic [ Time Frame: During the procedure ]
    prevalence of reader-detected TRFC from PD at 12 MHz harmonic frequency

  43. VoA prevalence of LRNC detection at 8 MHz fundamental [ Time Frame: During the procedure ]
    prevalence of reader-detected LRNC from VoA at 8 MHz fundamental frequency

  44. PD prevalence of LRNC detection at 8 MHz fundamental [ Time Frame: During the procedure ]
    prevalence of reader-detected LRNC from PD at 8 MHz fundamental frequency

  45. VoA prevalence of LRNC detection at 12 MHz fundamental [ Time Frame: During the procedure ]
    prevalence of reader-detected LRNC from VoA at 12 MHz fundamental frequency

  46. PD prevalence of LRNC detection at 12 MHz fundamental [ Time Frame: During the procedure ]
    prevalence of reader-detected LRNC from PD at 12 MHz fundamental frequency

  47. VoA prevalence of LRNC detection at 12 MHz harmonic [ Time Frame: During the procedure ]
    prevalence of reader-detected LRNC from VoA at 12 MHz harmonic frequency

  48. PD prevalence of LRNC detection at 12 MHz harmonic [ Time Frame: During the procedure ]
    prevalence of reader-detected LRNC from PD at 12 MHz harmonic frequency

  49. VoA prevalence of IPH detection at 8 MHz fundamental [ Time Frame: During the procedure ]
    prevalence of reader-detected IPH from VoA at 8 MHz fundamental frequency

  50. PD prevalence of IPH detection at 8 MHz fundamental [ Time Frame: During the procedure ]
    prevalence of reader-detected IPH from PD at 8 MHz fundamental frequency

  51. VoA prevalence of IPH detection at 12 MHz fundamental [ Time Frame: During the procedure ]
    prevalence of reader-detected IPH from VoA at 12 MHz fundamental frequency

  52. PD prevalence of IPH detection at 12 MHz fundamental [ Time Frame: During the procedure ]
    prevalence of reader-detected IPH from PD at 12 MHz fundamental frequency

  53. VoA prevalence of IPH detection at 12 MHz harmonic [ Time Frame: During the procedure ]
    prevalence of reader-detected IPH from VoA at 12 MHz harmonic frequency

  54. PD prevalence of IPH detection at 12 MHz harmonic [ Time Frame: During the procedure ]
    prevalence of reader-detected IPH from PD at 12 MHz harmonic frequency



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. aged 18 years or older
  2. having 50-99% stenotic symptomatic carotid plaque with clinical indication for endarterectomy
  3. having 50-69% stenotic asymptomatic carotid plaque without clinical indication for endarterectomy

Exclusion Criteria:

  1. prior CEA or carotid stenting
  2. carotid occlusion
  3. vasculitis
  4. malignancy
  5. inability to provide informed consent
  6. prior radiation therapy to the neck
  7. treatment with immunomodulating drugs
  8. oncological disease.

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): NCT04063709


Contacts
Layout table for location contacts
Contact: Melrose Fisher, RN 919-819-9054 mwfisher54@gmail.com
Contact: Caterina Gallippi, PhD 919-843-6647 cmgallip@email.unc.edu

Locations
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United States, North Carolina
The University of North Carolina at Chapel Hill Hospitals Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Melrose W Fisher, R.N.    919-819-9054    melrosef@email.unc.edu   
Contact: Caterina M Gallippi, Ph.D.    919-843-6647    cmgallip@email.unc.edu   
Sponsors and Collaborators
University of North Carolina, Chapel Hill
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Layout table for investigator information
Principal Investigator: Caterina Gallippi, PhD UNC Chapel Hill

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Responsible Party: University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT04063709     History of Changes
Other Study ID Numbers: 17-2700
R01HL092944-06A1 ( U.S. NIH Grant/Contract )
First Posted: August 21, 2019    Key Record Dates
Last Update Posted: August 21, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Deidentified individual data pertaining to the study protocol and the statistical analysis plan that support the results will be shared beginning 9 to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: Deidentified individual data pertaining to the study protocol and the statistical analysis plan that support the results will be shared beginning 9 to 36 months following publication.
Access Criteria: An investigator who proposes to use the data must have approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and execute a data use/sharing agreement with UNC.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Carotid Stenosis
Plaque, Atherosclerotic
Pathological Conditions, Anatomical
Carotid Artery Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases