Clinical trial NCT04063709: Transcutaneous ARFI Ultrasound for Differentiating Carotid Plaque With High Stroke Risk
Official title: Transcutaneous ARFI Ultrasound for Differentiating Carotid Plaque With High Stroke Risk
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Plaque, Atherosclerotic
Carotid Artery Plaque
Carotid Stenosis
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2019-08-21
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: DIAGNOSTIC

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.

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.

Eligibility 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.

Primary outcomes:
measure: Acoustic Radiation Force Impulse (ARFI) imaging
timeFrame: 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:
measure: VoA AUC for thin or ruptured fibrous caps (TRFC) at 8 MHz fundamental
timeFrame: 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
measure: PD AUC for TRFC at 8 MHz fundamental
timeFrame: 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
measure: VoA AUC for TRFC at 12 MHz fundamental
timeFrame: 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
measure: PD AUC for TRFC at 12 MHz fundamental
timeFrame: 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
measure: VoA AUC for TRFC at 12 MHz harmonic
timeFrame: 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
measure: PD AUC for TRFC at 12 MHz harmonic
timeFrame: 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
measure: VoA AUC for LRNC at 8 MHz fundamental
timeFrame: 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
measure: PD AUC for LRNC at 8 MHz fundamental
timeFrame: 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
measure: VoA AUC for LRNC at 12 MHz fundamental
timeFrame: 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
measure: PD AUC for LRNC at 12 MHz fundamental
timeFrame: 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
measure: VoA AUC for LRNC at 12 MHz harmonic
timeFrame: 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
measure: PD AUC for LRNC at 12 MHz harmonic
timeFrame: 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
measure: VoA AUC for IPH at 8 MHz fundamental
timeFrame: 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
measure: PD AUC for IPH at 8 MHz fundamental
timeFrame: 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
measure: VoA AUC for IPH at 12 MHz fundamental
timeFrame: 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
measure: PD AUC for IPH at 12 MHz fundamental
timeFrame: 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
measure: VoA AUC for IPH at 12 MHz harmonic
timeFrame: 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
measure: PD AUC for IPH at 12 MHz harmonic
timeFrame: 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
measure: VoA bias for TRFC thickness at 8 MHz fundamental
timeFrame: 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
measure: PD bias for TRFC thickness at 8 MHz fundamental
timeFrame: 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
measure: VoA bias for TRFC thickness at 12 MHz fundamental
timeFrame: 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
measure: PD bias for TRFC thickness at 12 MHz fundamental
timeFrame: 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
measure: VoA bias for TRFC thickness at 12 MHz harmonic
timeFrame: 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
measure: PD bias for TRFC thickness at 12 MHz harmonic
timeFrame: 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
measure: VoA bias for LRNC size at 8 MHz fundamental
timeFrame: 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
measure: PD bias for LRNC size at 8 MHz fundamental
timeFrame: 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
measure: VoA bias for LRNC size at 12 MHz fundamental
timeFrame: 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
measure: PD bias for LRNC size at 12 MHz fundamental
timeFrame: 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
measure: VoA bias for LRNC size at 12 MHz harmonic
timeFrame: 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
measure: PD bias for LRNC size at 12 MHz harmonic
timeFrame: 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
measure: VoA bias for IPH size at 8 MHz fundamental
timeFrame: 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
measure: PD bias for IPH size at 8 MHz fundamental
timeFrame: 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
measure: VoA bias for IPH size at 12 MHz fundamental
timeFrame: 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
measure: PD bias for IPH size at 12 MHz fundamental
timeFrame: 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
measure: VoA bias for IPH size at 12 MHz harmonic
timeFrame: 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
measure: PD bias for IPH size at 12 MHz harmonic
timeFrame: 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
measure: VoA prevalence of TRFC detection at 8 MHz fundamental
timeFrame: 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
measure: PD prevalence of TRFC detection at 8 MHz fundamental
timeFrame: 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
measure: VoA prevalence of TRFC detection at 12 MHz fundamental
timeFrame: 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
measure: PD prevalence of TRFC detection at 12 MHz fundamental
timeFrame: 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
measure: VoA prevalence of TRFC detection at 12 MHz harmonic
timeFrame: 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
measure: PD prevalence of TRFC detection at 12 MHz harmonic
timeFrame: 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
measure: VoA prevalence of LRNC detection at 8 MHz fundamental
timeFrame: 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
measure: PD prevalence of LRNC detection at 8 MHz fundamental
timeFrame: 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
measure: VoA prevalence of LRNC detection at 12 MHz fundamental
timeFrame: 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
measure: PD prevalence of LRNC detection at 12 MHz fundamental
timeFrame: 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
measure: VoA prevalence of LRNC detection at 12 MHz harmonic
timeFrame: 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
measure: PD prevalence of LRNC detection at 12 MHz harmonic
timeFrame: 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
measure: VoA prevalence of IPH detection at 8 MHz fundamental
timeFrame: 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
measure: PD prevalence of IPH detection at 8 MHz fundamental
timeFrame: 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
measure: VoA prevalence of IPH detection at 12 MHz fundamental
timeFrame: 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
measure: PD prevalence of IPH detection at 12 MHz fundamental
timeFrame: 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
measure: VoA prevalence of IPH detection at 12 MHz harmonic
timeFrame: 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
measure: PD prevalence of IPH detection at 12 MHz harmonic
timeFrame: 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
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: The University of North Carolina at Chapel Hill Hospitals
state: North Carolina
Study officials:
affiliation: UNC Chapel Hill
name: Caterina Gallippi, PhD
role: PRINCIPAL_INVESTIGATOR
References: