Early Detection of Vascular Dysfunction Using Biomarkers From Lagrangian Carotid Strain Imaging

Healthy Clinical Trial

Official title:

Early Detection of Vascular Dysfunction Using Biomarkers From Lagrangian Carotid Strain Imaging

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04632485
• Other study ID #: 2020-0384
• Secondary ID: A534800SMPH/MED
• Status: Recruiting
• Start date: September 9, 2021
• Est. completion date: July 2025

Study information

• Verified date: March 2024
• Source: University of Wisconsin, Madison
• Contact: Study Coordinator
• Phone: 608-263-7421
• Email: Radstudy[@]uwhealth.org
• Is FDA regulated: No
• Study type: Observational

Clinical 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'. 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 280
• Est. completion date: July 2025
• Est. primary completion date: July 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

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 Exclusion Criteria: 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 cardiac disease, stroke or TIA
• History of statin medication
• History of hypertension medications

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 participants 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)

Related Conditions & MeSH terms

• Carotid Artery Diseases
• Healthy

Intervention

Device:
• Ultrasound imaging
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)
Head and Neck MRI exam with contrast

Other:
• Neurocognitive testing
Harmonization battery to assess executive function/attention, speeded psychomotor, verbal, and nonverbal memory, language, and visuospatial skills

Device:
• Transcranial Doppler (TCD)
Use of a TCD system to monitor right and left middle cerebral artery Doppler waveforms in the volunteer for 60 minutes

Locations

Country	Name	City	State
United States	Department of Medical Physics, University of Wisconsin	Madison	Wisconsin

Sponsors (2)

Lead Sponsor	Collaborator
University of Wisconsin, Madison	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	up to 60 minute
Primary	Characterization of artery wall stiffness and possible plaque by using Ultrasound by clinical strain 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.	up to 60 minute
Primary	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.	up to 60 minute
Primary	Fasting Lipid panel Analysis	For aim-1 participants, a single fasting (10-12 hours) blood sample will be collected for a fasting lipid panel	up to 13 hours
Primary	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	up to 13 hours
Primary	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	up to 13 hours
Primary	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.	up to 60 minute