Plaque, AtheroscleroticNCT04063709
Transcutaneous ARFI Ultrasound for Differentiating Carotid Plaque With High Stroke Risk
A study testing Acoustic Radiation Force Impulse (ARFI) ultrasound in people with Plaque, Atherosclerotic and Carotid Artery Plaque, run by University of North Carolina, Chapel Hill at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Plaque, Atherosclerotic, Carotid Artery Plaque, Carotid Stenosis
- What is being tested?
- Acoustic Radiation Force Impulse (ARFI) ultrasound
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Jul 2019to Aug 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
The University of North Carolina at Chapel Hill Hospitals
Chapel Hill, North Carolina, 27599
About this study
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.
Read the 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.
- Being tested
- Acoustic Radiation Force Impulse (ARFI) ultrasound
- Medical subject headings
- Plaque, Atherosclerotic, Carotid Stenosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Acoustic Radiation Force Impulse (ARFI) ultrasoundDiagnostic test
ARFI imaging is an ultrasound-based, noninvasive imaging method and will be used in accordance with approved labeling.
| Study group | Role | What they receive |
|---|---|---|
| Symptomatic with 50-69% stenosis | Experimental | 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. Receives: Diagnostic Test: Acoustic Radiation Force Impulse (ARFI) ultrasound |
| Symptomatic with 70-99% stenosis | Experimental | 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. Receives: Diagnostic Test: Acoustic Radiation Force Impulse (ARFI) ultrasound |
| Asymptomatic with 70-99% stenosis | Experimental | 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. Receives: Diagnostic Test: Acoustic Radiation Force Impulse (ARFI) ultrasound |
| Asymptomatic with 50-69% stenosis | Experimental | Patients 18 years of age or older who have been diagnosed with 50-69% carotid artery stenosis without clinical indication for CEA. Receives: Diagnostic Test: Acoustic Radiation Force Impulse (ARFI) ultrasound |
What is being measured
The primary outcome is the main question the study is designed to answer.
Acoustic Radiation Force Impulse (ARFI) imaging
Ability of ARFI imaging to detect carotid plaque features and measure their size
Measured: 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
Secondary outcomes (54)
VoA AUC for thin or ruptured fibrous caps (TRFC) at 8 MHz fundamental
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
Measured: 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
PD AUC for TRFC at 8 MHz fundamental
AUC for the ability of ARFI PD obtained at 8 MHz fundamental frequency to detect thin or ruptured fibrous cap
Measured: 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
VoA AUC for TRFC at 12 MHz fundamental
AUC for the ability of ARFI VoA obtained at 12 MHz fundamental frequency to detect thin or ruptured fibrous cap
Measured: 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
PD AUC for TRFC at 12 MHz fundamental
AUC for the ability of ARFI PD obtained at 12 MHz fundamental frequency to detect thin or ruptured fibrous cap
Measured: 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
VoA AUC for TRFC at 12 MHz harmonic
AUC for the ability of ARFI VoA obtained at 12 MHz harmonic frequency to detect thin or ruptured fibrous cap
Measured: 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
PD AUC for TRFC at 12 MHz harmonic
AUC for the ability of ARFI PD obtained at 12 MHz harmonic frequency to detect thin or ruptured fibrous cap
Measured: 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
VoA AUC for LRNC at 8 MHz fundamental
AUC for the ability of ARFI VoA obtained at 8 MHz fundamental frequency to detect lipid rich necrotic core (LRNC)
Measured: 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
PD AUC for LRNC at 8 MHz fundamental
AUC for the ability of ARFI PD obtained at 8 MHz fundamental frequency to detect lipid rich necrotic core
Measured: 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
VoA AUC for LRNC at 12 MHz fundamental
AUC for the ability of ARFI VoA obtained at 12 MHz fundamental frequency to detect lipid rich necrotic core
Measured: 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
PD AUC for LRNC at 12 MHz fundamental
AUC for the ability of ARFI PD obtained at 12 MHz fundamental frequency to detect lipid rich necrotic core
Measured: 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
VoA AUC for LRNC at 12 MHz harmonic
AUC for the ability of ARFI VoA obtained at 12 MHz harmonic frequency to detect lipid rich necrotic core
Measured: 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
PD AUC for LRNC at 12 MHz harmonic
AUC for the ability of ARFI PD obtained at 12 MHz harmonic frequency to detect lipid rich necrotic core
Measured: 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
VoA AUC for IPH at 8 MHz fundamental
AUC for the ability of ARFI VoA obtained at 8 MHz fundamental frequency to detect intraplaque hemorrhage
Measured: 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
PD AUC for IPH at 8 MHz fundamental
AUC for the ability of ARFI PD obtained at 8 MHz fundamental frequency to detect intraplaque hemorrhage
Measured: 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
VoA AUC for IPH at 12 MHz fundamental
AUC for the ability of ARFI VoA obtained at 12 MHz fundamental frequency to detect intraplaque hemorrhage
Measured: 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
PD AUC for IPH at 12 MHz fundamental
AUC for the ability of ARFI PD obtained at 12 MHz fundamental frequency to detect intraplaque hemorrhage
Measured: 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
VoA AUC for IPH at 12 MHz harmonic
AUC for the ability of ARFI VoA obtained at 12 MHz harmonic frequency to detect intraplaque hemorrhage
Measured: 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
PD AUC for IPH at 12 MHz harmonic
AUC for the ability of ARFI PD obtained at 12 MHz harmonic frequency to detect intraplaque hemorrhage
Measured: 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
VoA bias for TRFC thickness at 8 MHz fundamental
Bland Altman-derived bias in VoA-based TRFC thickness measurement 8 MHz fundamental frequency
Measured: 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
PD bias for TRFC thickness at 8 MHz fundamental
Bland Altman-derived bias in PD-based TRFC thickness measurement 8 MHz fundamental frequency
Measured: 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
VoA bias for TRFC thickness at 12 MHz fundamental
Bland Altman-derived bias in VoA-based TRFC thickness measurement at 12 MHz fundamental frequency
Measured: 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
PD bias for TRFC thickness at 12 MHz fundamental
Bland Altman-derived bias in PD-based TRFC thickness measurement at 12 MHz fundamental frequency
Measured: 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
VoA bias for TRFC thickness at 12 MHz harmonic
Bland Altman-derived bias in VoA-based TRFC thickness measurement at 12 MHz harmonic frequency
Measured: 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
PD bias for TRFC thickness at 12 MHz harmonic
Bland Altman-derived bias in PD-based TRFC thickness measurement at 12 MHz harmonic frequency
Measured: 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
VoA bias for LRNC size at 8 MHz fundamental
Bland Altman-derived bias in VoA-based LRNC size measurement at 8 MHz fundamental frequency
Measured: 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
PD bias for LRNC size at 8 MHz fundamental
Bland Altman-derived bias in PD-based LRNC size measurement at 8 MHz fundamental frequency
Measured: 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
VoA bias for LRNC size at 12 MHz fundamental
Bland Altman-derived bias in VoA-based LRNC size measurement at 12 MHz fundamental frequency
Measured: 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
PD bias for LRNC size at 12 MHz fundamental
Bland Altman-derived bias in PD-based LRNC size measurement at 12 MHz fundamental frequency
Measured: 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
VoA bias for LRNC size at 12 MHz harmonic
Bland Altman-derived bias in VoA-based LRNC size measurement at 12 MHz harmonic frequency
Measured: 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
PD bias for LRNC size at 12 MHz harmonic
Bland Altman-derived bias in PD-based LRNC size measurement at 12 MHz harmonic frequency
Measured: 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
VoA bias for IPH size at 8 MHz fundamental
Bland Altman-derived bias in VoA-based IPH size measurement at 8 MHz fundamental frequency
Measured: 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
PD bias for IPH size at 8 MHz fundamental
Bland Altman-derived bias in PD-based IPH size measurement at 8 MHz fundamental frequency
Measured: 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
VoA bias for IPH size at 12 MHz fundamental
Bland Altman-derived bias in VoA-based IPH size measurement at 12 MHz fundamental frequency
Measured: 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
PD bias for IPH size at 12 MHz fundamental
Bland Altman-derived bias in PD-based IPH size measurement at 12 MHz fundamental frequency
Measured: 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
VoA bias for IPH size at 12 MHz harmonic
Bland Altman-derived bias in VoA-based IPH size measurement at 12 MHz harmonic frequency
Measured: 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
PD bias for IPH size at 12 MHz harmonic
Bland Altman-derived bias in PD-based IPH size measurement at 12 MHz harmonic frequency
Measured: 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
VoA prevalence of TRFC detection at 8 MHz fundamental
prevalence of reader-detected TRFC from VoA at 8 MHz fundamental frequency
Measured: 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
PD prevalence of TRFC detection at 8 MHz fundamental
prevalence of reader-detected TRFC from PD at 8 MHz fundamental frequency
Measured: 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
VoA prevalence of TRFC detection at 12 MHz fundamental
prevalence of reader-detected TRFC from VoA at 12 MHz fundamental frequency
Measured: 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
PD prevalence of TRFC detection at 12 MHz fundamental
prevalence of reader-detected TRFC from PD at 12 MHz fundamental frequency
Measured: 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
VoA prevalence of TRFC detection at 12 MHz harmonic
prevalence of reader-detected TRFC from VoA at 12 MHz harmonic frequency
Measured: 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
PD prevalence of TRFC detection at 12 MHz harmonic
prevalence of reader-detected TRFC from PD at 12 MHz harmonic frequency
Measured: 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
VoA prevalence of LRNC detection at 8 MHz fundamental
prevalence of reader-detected LRNC from VoA at 8 MHz fundamental frequency
Measured: 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
PD prevalence of LRNC detection at 8 MHz fundamental
prevalence of reader-detected LRNC from PD at 8 MHz fundamental frequency
Measured: 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
VoA prevalence of LRNC detection at 12 MHz fundamental
prevalence of reader-detected LRNC from VoA at 12 MHz fundamental frequency
Measured: 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
PD prevalence of LRNC detection at 12 MHz fundamental
prevalence of reader-detected LRNC from PD at 12 MHz fundamental frequency
Measured: 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
VoA prevalence of LRNC detection at 12 MHz harmonic
prevalence of reader-detected LRNC from VoA at 12 MHz harmonic frequency
Measured: 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
PD prevalence of LRNC detection at 12 MHz harmonic
prevalence of reader-detected LRNC from PD at 12 MHz harmonic frequency
Measured: 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
VoA prevalence of IPH detection at 8 MHz fundamental
prevalence of reader-detected IPH from VoA at 8 MHz fundamental frequency
Measured: 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
PD prevalence of IPH detection at 8 MHz fundamental
prevalence of reader-detected IPH from PD at 8 MHz fundamental frequency
Measured: 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
VoA prevalence of IPH detection at 12 MHz fundamental
prevalence of reader-detected IPH from VoA at 12 MHz fundamental frequency
Measured: 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
PD prevalence of IPH detection at 12 MHz fundamental
prevalence of reader-detected IPH from PD at 12 MHz fundamental frequency
Measured: 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
VoA prevalence of IPH detection at 12 MHz harmonic
prevalence of reader-detected IPH from VoA at 12 MHz harmonic frequency
Measured: 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
PD prevalence of IPH detection at 12 MHz harmonic
prevalence of reader-detected IPH from PD at 12 MHz harmonic frequency
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2019
- Study start17 Jul 2019
- Primary completionAug 2027 (estimated)
- Study completionAug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Plaque, AtheroscleroticStudies of the same condition, open and under way.
- More trials run by University of North Carolina, Chapel HillThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- 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)
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor
- Investigators
- Caterina Gallippi, PhD, Principal investigator, UNC Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04063709
- Sponsor's protocol ID
- 17-2700
- Other IDs
- R01HL092944-06A1
- Status last verified
- Sep 2026
- First submitted
- 16 Aug 2019
- Last updated
- 14 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Transcutaneous ARFI Ultrasound for Differentiating Carotid Plaque With High Stroke Risk
- ClinicalTrials.gov ID
- NCT04063709
- Acronym / sponsor ID
- 17-2700
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 72 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 17 Jul 2019 (actual)
- Primary completion
- Aug 2027 (estimated)
- Study completion
- Aug 2027 (estimated)
- First posted
- 21 Aug 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- 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.
| Arm | Type | Receives |
|---|---|---|
| Symptomatic with 50-69% stenosis | Experimental | Diagnostic Test: Acoustic Radiation Force Impulse (ARFI) ultrasoundPatients 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. |
| Symptomatic with 70-99% stenosis | Experimental | Diagnostic Test: Acoustic Radiation Force Impulse (ARFI) ultrasoundPatients 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. |
| Asymptomatic with 70-99% stenosis | Experimental | Diagnostic Test: Acoustic Radiation Force Impulse (ARFI) ultrasoundPatients 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. |
| Asymptomatic with 50-69% stenosis | Experimental | Diagnostic Test: Acoustic Radiation Force Impulse (ARFI) ultrasoundPatients 18 years of age or older who have been diagnosed with 50-69% carotid artery stenosis without clinical indication for CEA. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (8 listed)
- prior CEA or carotid stenting
- carotid occlusion
- vasculitis
- malignancy
- inability to provide informed consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Acoustic Radiation Force Impulse (ARFI) ultrasoundARFI imaging is an ultrasound-based, noninvasive imaging method and will be used in accordance with approved labeling. | Diagnostic test | Asymptomatic with 50-69% stenosis, Asymptomatic with 70-99% stenosis, Symptomatic with 50-69% stenosis, Symptomatic with 70-99% stenosis |
Primary outcome
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
54 secondary outcomes
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2026.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Caterina Gallippi, PhD principal investigator
UNC Chapel Hill
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Acoustic Radiation Force Impulse (ARFI) ultrasound in people with Plaque, Atherosclerotic and Carotid Artery Plaque, run by University of North Carolina, Chapel Hill at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 14 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2026.