HealthyNCT04632485
Early Detection of Vascular Dysfunction Using Biomarkers From Lagrangian Carotid Strain Imaging
An observational study of Healthy and Carotid Artery Diseases, run by University of Wisconsin, Madison at 1 site in United States.
Trial summary
The purpose of this research is assess imaging and identification of soft plaque that undergoes large deformations or strain will identify plaque vulnerable to rupture which could lead to 'silent strokes'. Read more about this study
- Who is it for?
- Ages 18 to 89 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy, Carotid Artery Diseases
- What is being tested?
- Ultrasound imaging, Magnetic Resonance Imaging (MRI) and Neurocognitive testing
- Type of treatment
- Medical device
- How many people
- 217 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Sep 2021to 30 Jun 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
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 to 89 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: This research will enroll 280 adult participants. 40 participants will be invited to participate in the longitudinal Ultrasound and Magnetic Resonance Imaging study if they are determined to be "at-risk" per current clinical guidelines for being in the at risk population.
Who may be able to join
- Aim 1 (Ultrasound (US) only):
- Adults at least 18 years
- Are able to provide written informed consent on their own behalf
- Aim 2 (US and MRI):
- Participation in the US study (Aim 1)
- Determined by presence of hypoechogenic or echolucent lipid-rich soft plaque during initial ultrasound imaging session
- Adults willing to participate over 5 years
Who cannot join
- Aim 1 (US only)
- Women that are currently pregnant
- Inability to cooperate with the ultrasound study, in particular those unable to sit without gross movement for the duration the ultrasound study (estimated at 60-90 minutes)
- Open wounds or sores in the anterior neck
- History of cancer treatment, vascular disease, cardiac disease, stroke or TIA
- History of medications that affect vascular wall and plaque
Show all 20Show fewer
- History of statin medications*
- History of hypertension medications*
- History of anticoagulation, blood thinners
- These criteria will not be exclusionary for the cohort that is greater than 70 years of age.
- Aim 2 (US and MRI):
- Women that are currently pregnant
- Inability to cooperate with the ultrasound study, in particular those unable to sit without gross movement for the duration the ultrasound study (estimated at 60-90 minutes)
- Patients that require intravenous (IV) conscious sedation for imaging are not eligible; patients requiring mild, oral anxiolytics for research imaging will be allowed to participate as long as the following criteria are met:
- The participant has their own prescription for the medication;
- The informed consent process is conducted prior to the self-administration of this medication; and,
- The participant comes to the research visit with a driver
- Contraindications to MR
- Unable to lie in the MRI scanner for 45-60 minutes
- Patients with a contraindication to gadolinium based contrast agents, including allergy or impaired renal function (per University of Wisconsin Health Guidelines)
Trial locations and contacts
1 site in 1 country.
United States1 site
Department of Medical Physics, University of Wisconsin
Madison, Wisconsin, 53705
About this study
The purpose of this research is assess imaging and identification of soft plaque that undergoes large deformations or strain will identify plaque vulnerable to rupture which could lead to 'silent strokes'. Validation of current study results with MRI will foster use of real-time ultrasound (US) strain imaging and strain indices as a screening tool for identifying normal human participants susceptible to increased vascular aging and developing plaque prone to rupture or micro-embolization.
Current research will evaluate Lagrangian carotid strain imaging (LCSI) for prediction of vascular health on volunteers. In this study, investigators will evaluate age-related strain variations (due to plaque deposition) in the carotid artery, establishing groundwork that will help identify typical and atypical values for these indices. Investigator's hypothesis is that plaques with higher strain indices (softer plaques) are more prone to rupture than plaques with lower strain indices (stiffer) plaques, thus requiring intervention. Clinical criteria for treatment has focused primarily on the degree of stenosis. Long-term objectives are to provide non-invasive methods for screening participants at risk for vascular aging or plaque rupture in asymptomatic participants, expanding upon current criteria for risk assessments based on focal transient ischemic attack (TIA) or strokes. Variations in vessel strain have been associated with, or are precursors to, plaque deposition, vascular aging, or cerebrovascular diseases. Increased arterial strain and pressure changes have been linked to brain aging using magnetic resonance imaging (MRI) based vascular indices, and memory deficits commonly linked to Alzheimer dementia. Stiffening and thickening of the arterial walls have also been associated with cerebrovascular disease. Investigators hypothesize that strain indices as vascular biomarkers can be utilized for screening possible 'vulnerable participants' validated with MRI, with the potential ability to improve endothelial function and reverse vascular aging. Strain indices may enable differentiating study participants with vascular cognitive impairment (VCI) from other dementias. Cognitive testing is unable to make this differentiation.
- Conditions
- Healthy, Carotid Artery Diseases
- Being tested
- Ultrasound imaging, Magnetic Resonance Imaging (MRI), Neurocognitive testing, Transcranial Doppler (TCD), Pulse Wave Doppler
- Medical subject headings
- Carotid Artery Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ultrasound imagingDevice
Carotid artery ultrasound exam. US imaging will include complete clinical carotid ultrasound examination (B-mode, Doppler and color-flow modes), clinical strain and shear wave imaging study, backscattered and beam-steered radiofrequency (RF) data acquisition using research mode, and reference phantom RF data acquisition.
Magnetic Resonance Imaging (MRI)Device
Head and Neck MRI exam with contrast
Neurocognitive testingOther
Harmonization battery to assess executive function/attention, speeded psychomotor, verbal, and nonverbal memory, language, and visuospatial skills
Transcranial Doppler (TCD)Device
Use of a TCD system to monitor right and left middle cerebral artery Doppler waveforms in the volunteer for 60 minutes
Pulse Wave DopplerDevice
Pulse wave Doppler will be used to acquire a Doppler waveform in the right common carotid artery and the right femoral artery
| Study group | Role | What they receive |
|---|---|---|
| Aim 1: Ultrasound Only | Approximately 280 asymptomatic participants will participate in ultrasound (US) studies and blood work. Receives: Device: Ultrasound imaging | |
| Aim 2: Ultrasound and MRI | A sub-group of 40 at risk volunteers determined from the clinical ultrasound scans and bloodwork from Aim 1 will be asked to participate in a longitudinal US and MRI study. Participants will be selected from a population of individuals that do not have significant atherosclerosis, but present with increased risk due to the presence of soft, lipid rich plaque that are hypoechogenic or echolucent on ultrasound B-mode images. These participants may also satisfy the current clinical guidelines of increased vessel diameter and decreased blood flow velocity with ultrasound that may result in plaque deposition for being in the at risk population. Participants will receive US, strain and shear wave imaging every 2 years after the first scan in Aim 1 and MRI Imaging in Year 1 and Year 5: separated by 4 years Receives: Device: Ultrasound imaging; Device: Magnetic Resonance Imaging (MRI); Other: Neurocognitive testing; Device: Transcranial Doppler (TCD); Device: Pulse Wave Doppler |
What is being measured
The primary outcome is the main question the study is designed to answer.
Characterization of artery wall stiffness and possible plaque by capturing B-mode, Doppler and color-flow modes of Ultrasound
Participants will receive complete clinical carotid ultrasound examination. B-mode, Doppler and color-flow modes of Ultrasound will be captured. This measure will characterize artery wall stiffness and possible plaque by using Ultrasound.
Measured: up to 60 minute
Characterization of artery wall stiffness and possible plaque by using radiofrequency ultrasound signals to estimate strain tensors, pulse wave velocity (PWV), and shear wave imaging
Participants will receive complete clinical carotid ultrasound examination. Clinical strain and shear wave imaging will be performed. This measure will characterize artery wall stiffness and possible plaque by using Ultrasound.
Measured: up to 60 minute
Carotid artery ultrasound examination for Aim-1 participants: backscattered and beam-steered RF data acquisition using research mode
Participants will receive complete clinical carotid ultrasound examination. Backscattered and beam-steered RF data acquisition using research mode, and reference phantom RF data acquisition will be performed. This measure will characterize artery wall stiffness and possible plaque by using Ultrasound.
Measured: up to 60 minute
Fasting Lipid panel Analysis
For aim-1 participants, a single fasting (10-12 hours) blood sample will be collected for a fasting lipid panel
Measured: up to 13 hours
Hemoglobin A1C test for diabetes
For aim-1 participants, a single fasting (10-12 hours) blood sample will be collected for a Hemoglobin A1C test
Measured: up to 13 hours
High-sensitivity C-reactive protein (HS-CRP) test for inflammatory markers for Aim 1 participants
For aim-1 participants, a single fasting (10-12 hours) blood sample will be collected for High-sensitivity C-reactive protein (HS-CRP) test
Measured: up to 13 hours
Detection of Plaques by MRI- Accuracy of MRI detection method as compared to Ultrasound and blood work
Longitudinal Ultrasound strain and MRI study will be performed on on a sub-group of 40(aim-2) at risk participants determined from the clinical ultrasound scans and bloodwork from Aim 1. This subgroup meet the criteria for being in a higher risk group for atherosclerosis or those with softer lipid-rich plaque (hypoechogenic or lower brightness on ultrasound).
Participants will be contacted on the phone to discuss these incidental findings and to request if they would be interested in participating in follow-up MRI, US and strain. MRI results will be compared to previous Ultrasound and blood work results to test the accuracy of MRI method in detecting plaques.
Measured: up to 60 minute
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2020
- Study start9 Sep 2021
- Primary completion30 Jun 2025
- Study completion30 Jun 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by University of Wisconsin, MadisonThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 217 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Wisconsin, Madison
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor
- Investigators
- Tomy Varghese, PhD, Principal investigator, University of Wisconsin, Madison
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04632485
- Sponsor's protocol ID
- 2020-0384
- Other IDs
- A534800, SMPH/MED PHYSICS, 2/12/2025, 1R01HL147866-01A1
- Status last verified
- Jul 2025
- First submitted
- 27 Oct 2020
- Last updated
- 2 Jul 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Detection of Vascular Dysfunction Using Biomarkers From Lagrangian Carotid Strain Imaging
- ClinicalTrials.gov ID
- NCT04632485
- Acronym / sponsor ID
- 2020-0384
- Conditions
- Healthy, Carotid Artery Diseases
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 217 participants (actual)
- Lead sponsor
- University of Wisconsin, MadisonUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 9 Sep 2021 (actual)
- Primary completion
- 30 Jun 2025 (actual)
- Study completion
- 30 Jun 2025 (actual)
- First posted
- 17 Nov 2020 (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.
The purpose of this research is assess imaging and identification of soft plaque that undergoes large deformations or strain will identify plaque vulnerable to rupture which could lead to 'silent strokes'. Validation of current study results with MRI will foster use of real-time ultrasound (US) strain imaging and strain indices as a screening tool for identifying normal human participants susceptible to increased vascular aging and developing plaque prone to rupture or micro-embolization.
Current research will evaluate Lagrangian carotid strain imaging (LCSI) for prediction of vascular health on volunteers. In this study, investigators will evaluate age-related strain variations (due to plaque deposition) in the carotid artery, establishing groundwork that will help identify typical and atypical values for these indices. Investigator's hypothesis is that plaques with higher strain indices (softer plaques) are more prone to rupture than plaques with lower strain indices (stiffer) plaques, thus requiring intervention. Clinical criteria for treatment has focused primarily on the degree of stenosis. Long-term objectives are to provide non-invasive methods for screening participants at risk for vascular aging or plaque rupture in asymptomatic participants, expanding upon current criteria for risk assessments based on focal transient ischemic attack (TIA) or strokes. Variations in vessel strain have been associated with, or are precursors to, plaque deposition, vascular aging, or cerebrovascular diseases. Increased arterial strain and pressure changes have been linked to brain aging using magnetic resonance imaging (MRI) based vascular indices, and memory deficits commonly linked to Alzheimer dementia. Stiffening and thickening of the arterial walls have also been associated with cerebrovascular disease. Investigators hypothesize that strain indices as vascular biomarkers can be utilized for screening possible 'vulnerable participants' validated with MRI, with the potential ability to improve endothelial function and reverse vascular aging. Strain indices may enable differentiating study participants with vascular cognitive impairment (VCI) from other dementias. Cognitive testing is unable to make this differentiation.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Aim 1: Ultrasound Only | – | Device: Ultrasound imagingApproximately 280 asymptomatic participants will participate in ultrasound (US) studies and blood work. |
| Aim 2: Ultrasound and MRI | – | Device: Ultrasound imaging, Device: Magnetic Resonance Imaging (MRI), Other: Neurocognitive testing, Device: Transcranial Doppler (TCD), Device: Pulse Wave DopplerA sub-group of 40 at risk volunteers determined from the clinical ultrasound scans and bloodwork from Aim 1 will be asked to participate in a longitudinal US and MRI study. Participants will be selected from a population of individuals that do not have significant atherosclerosis, but present with increased risk due to the presence of soft, lipid rich plaque that are hypoechogenic or echolucent on ultrasound B-mode images. These participants may also satisfy the current clinical guidelines of increased vessel diameter and decreased blood flow velocity with ultrasound that may result in plaque deposition for being in the at risk population. Participants will receive US, strain and shear wave imaging every 2 years after the first scan in Aim 1 and MRI Imaging in Year 1 and Year 5: separated by 4 years |
Who may qualify
- Ages
- 18 to 89 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- This research will enroll 280 adult participants. 40 participants will be invited to participate in the longitudinal Ultrasound and Magnetic Resonance Imaging study if they are determined to be "at-risk" per current clinical guidelines for being in the at risk population.
Key inclusion criteria (7 listed)
- Adults at least 18 years
- Are able to provide written informed consent on their own behalf
- Participation in the US study (Aim 1)
- Determined by presence of hypoechogenic or echolucent lipid-rich soft plaque during initial ultrasound imaging session
- Adults willing to participate over 5 years
Key exclusion criteria (20 listed)
- Aim 1 (US only)
- Women that are currently pregnant
- Inability to cooperate with the ultrasound study, in particular those unable to sit without gross movement for the duration the ultrasound study (estimated at 60-90 minutes)
- Open wounds or sores in the anterior neck
- History of cancer treatment, vascular disease, cardiac disease, stroke or TIA
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 |
|---|---|---|
| Ultrasound imagingCarotid artery ultrasound exam. US imaging will include complete clinical carotid ultrasound examination (B-mode, Doppler and color-flow modes), clinical strain and shear wave imaging study, backscattered and beam-steered radiofrequency (RF) data acquisition using research mode, and reference phantom RF data acquisition. | Device | Aim 1: Ultrasound Only, Aim 2: Ultrasound and MRI |
| Magnetic Resonance Imaging (MRI)Head and Neck MRI exam with contrast | Device | Aim 2: Ultrasound and MRI |
| Neurocognitive testingHarmonization battery to assess executive function/attention, speeded psychomotor, verbal, and nonverbal memory, language, and visuospatial skills | Other | Aim 2: Ultrasound and MRI |
| Transcranial Doppler (TCD)Use of a TCD system to monitor right and left middle cerebral artery Doppler waveforms in the volunteer for 60 minutes | Device | Aim 2: Ultrasound and MRI |
| Pulse Wave DopplerPulse wave Doppler will be used to acquire a Doppler waveform in the right common carotid artery and the right femoral artery | Device | Aim 2: Ultrasound and MRI |
Primary outcome
Characterization of artery wall stiffness and possible plaque by capturing B-mode, Doppler and color-flow modes of Ultrasound
Time frame: up to 60 minute
Participants will receive complete clinical carotid ultrasound examination. B-mode, Doppler and color-flow modes of Ultrasound will be captured. This measure will characterize artery wall stiffness and possible plaque by using Ultrasound.
Characterization of artery wall stiffness and possible plaque by using radiofrequency ultrasound signals to estimate strain tensors, pulse wave velocity (PWV), and shear wave imaging
Time frame: up to 60 minute
Participants will receive complete clinical carotid ultrasound examination. Clinical strain and shear wave imaging will be performed. This measure will characterize artery wall stiffness and possible plaque by using Ultrasound.
Carotid artery ultrasound examination for Aim-1 participants: backscattered and beam-steered RF data acquisition using research mode
Time frame: up to 60 minute
Participants will receive complete clinical carotid ultrasound examination. Backscattered and beam-steered RF data acquisition using research mode, and reference phantom RF data acquisition will be performed. This measure will characterize artery wall stiffness and possible plaque by using Ultrasound.
Fasting Lipid panel Analysis
Time frame: up to 13 hours
For aim-1 participants, a single fasting (10-12 hours) blood sample will be collected for a fasting lipid panel
Hemoglobin A1C test for diabetes
Time frame: up to 13 hours
For aim-1 participants, a single fasting (10-12 hours) blood sample will be collected for a Hemoglobin A1C test
High-sensitivity C-reactive protein (HS-CRP) test for inflammatory markers for Aim 1 participants
Time frame: up to 13 hours
For aim-1 participants, a single fasting (10-12 hours) blood sample will be collected for High-sensitivity C-reactive protein (HS-CRP) test
Detection of Plaques by MRI- Accuracy of MRI detection method as compared to Ultrasound and blood work
Time frame: up to 60 minute
Longitudinal Ultrasound strain and MRI study will be performed on on a sub-group of 40(aim-2) at risk participants determined from the clinical ultrasound scans and bloodwork from Aim 1. This subgroup meet the criteria for being in a higher risk group for atherosclerosis or those with softer lipid-rich plaque (hypoechogenic or lower brightness on ultrasound). Participants will be contacted on the phone to discuss these incidental findings and to request if they would be interested in participating in follow-up MRI, US and strain. MRI results will be compared to previous Ultrasound and blood work results to test the accuracy of MRI method in detecting plaques.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2025.
- Individual participant dataSharing planned: No
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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.
Tomy Varghese, PhD principal investigator
University of Wisconsin, Madison
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Healthy and Carotid Artery Diseases, run by University of Wisconsin, Madison 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 7 inclusion and 20 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: finished, as of the sponsor's last update on 2 Jul 2025. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Characterization of artery wall stiffness and possible plaque by capturing B-mode, Doppler and color-flow modes of Ultrasound (time frame: up to 60 minute). The study lists 7 primary outcomes in all. 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 2 Jul 2025.