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Active, Not Recruiting

NCT Number: NCT04063709

Transcutaneous ARFI Ultrasound for Differentiating Carotid Plaque With High Stroke Risk

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Plaque, Atherosclerotic Arterial Occlusive Diseases Brain Diseases Cardiovascular Diseases Carotid Artery Diseases Carotid Artery Plaque Carotid Stenosis Central Nervous System Diseases Cerebrovascular Disorders Nervous System Diseases Pathological Conditions, Anatomical Pathological Conditions, Signs and Symptoms Vascular Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

The University of North Carolina at Chapel Hill Hospitals

Chapel Hill, North Carolina, 27599, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

  • prior CEA or carotid stenting
  • carotid occlusion
  • vasculitis
  • malignancy
  • inability to provide informed consent
  • prior radiation therapy to the neck
  • treatment with immunomodulating drugs
  • oncological disease.

Treatment and study plan

Acoustic Radiation Force Impulse (ARFI) ultrasound

Diagnostic Test

ARFI imaging is an ultrasound-based, noninvasive imaging method and will be used in accordance with approved labeling.

Primary outcomes

  1. Acoustic Radiation Force Impulse (ARFI) imaging

    Time frame: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    Ability of ARFI imaging to detect carotid plaque features and measure their size

Secondary outcomes

  1. VoA AUC for thin or ruptured fibrous caps (TRFC) at 8 MHz fundamental

    Time frame: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    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: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    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: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    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: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    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: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    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: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    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: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    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: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    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: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    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: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    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: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    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: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    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: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    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: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    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: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    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: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    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: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    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: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    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: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    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: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    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: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    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: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    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: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    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: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    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: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    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: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    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: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    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: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    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: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    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: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    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: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    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: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    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: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    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: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    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: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    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: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    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: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    prevalence of reader-detected TRFC from VoA at 8 MHz fundamental frequency

  38. PD prevalence of TRFC detection at 8 MHz fundamental

    Time frame: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    prevalence of reader-detected TRFC from PD at 8 MHz fundamental frequency

  39. VoA prevalence of TRFC detection at 12 MHz fundamental

    Time frame: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    prevalence of reader-detected TRFC from VoA at 12 MHz fundamental frequency

  40. PD prevalence of TRFC detection at 12 MHz fundamental

    Time frame: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    prevalence of reader-detected TRFC from PD at 12 MHz fundamental frequency

  41. VoA prevalence of TRFC detection at 12 MHz harmonic

    Time frame: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    prevalence of reader-detected TRFC from VoA at 12 MHz harmonic frequency

  42. PD prevalence of TRFC detection at 12 MHz harmonic

    Time frame: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    prevalence of reader-detected TRFC from PD at 12 MHz harmonic frequency

  43. VoA prevalence of LRNC detection at 8 MHz fundamental

    Time frame: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    prevalence of reader-detected LRNC from VoA at 8 MHz fundamental frequency

  44. PD prevalence of LRNC detection at 8 MHz fundamental

    Time frame: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    prevalence of reader-detected LRNC from PD at 8 MHz fundamental frequency

  45. VoA prevalence of LRNC detection at 12 MHz fundamental

    Time frame: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    prevalence of reader-detected LRNC from VoA at 12 MHz fundamental frequency

  46. PD prevalence of LRNC detection at 12 MHz fundamental

    Time frame: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    prevalence of reader-detected LRNC from PD at 12 MHz fundamental frequency

  47. VoA prevalence of LRNC detection at 12 MHz harmonic

    Time frame: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    prevalence of reader-detected LRNC from VoA at 12 MHz harmonic frequency

  48. PD prevalence of LRNC detection at 12 MHz harmonic

    Time frame: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    prevalence of reader-detected LRNC from PD at 12 MHz harmonic frequency

  49. VoA prevalence of IPH detection at 8 MHz fundamental

    Time frame: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    prevalence of reader-detected IPH from VoA at 8 MHz fundamental frequency

  50. PD prevalence of IPH detection at 8 MHz fundamental

    Time frame: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    prevalence of reader-detected IPH from PD at 8 MHz fundamental frequency

  51. VoA prevalence of IPH detection at 12 MHz fundamental

    Time frame: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    prevalence of reader-detected IPH from VoA at 12 MHz fundamental frequency

  52. PD prevalence of IPH detection at 12 MHz fundamental

    Time frame: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    prevalence of reader-detected IPH from PD at 12 MHz fundamental frequency

  53. VoA prevalence of IPH detection at 12 MHz harmonic

    Time frame: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    prevalence of reader-detected IPH from VoA at 12 MHz harmonic frequency

  54. PD prevalence of IPH detection at 12 MHz harmonic

    Time frame: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

    prevalence of reader-detected IPH from PD at 12 MHz harmonic frequency

Sponsors and collaborators

Lead sponsor

University of North Carolina, Chapel Hill

Other

Collaborators

  • National Heart, Lung, and Blood Institute (NHLBI)

Registry information

Important dates

Study start
2019
Primary completion
2025
Study completion
2025
First posted
Aug 21, 2019
Registry last updated
Feb 7, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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