Clinical trial NCT04632485: Early Detection of Vascular Dysfunction Using Biomarkers From Lagrangian Carotid Strain Imaging
Official title: Early Detection of Vascular Dysfunction Using Biomarkers From Lagrangian Carotid Strain Imaging
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Healthy
Carotid Artery Diseases
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2020-11-17
Enrollment: 217
Sex: ALL
Minimum age (years): 18
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
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.

Brief 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.


Eligibility criteria: 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 cancer treatment, vascular disease, cardiac disease, stroke or TIA
* History of medications that affect vascular wall and plaque
* 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)

Primary outcomes:
measure: Characterization of artery wall stiffness and possible plaque by capturing B-mode, Doppler and color-flow modes of Ultrasound
timeFrame: up to 60 minute
measure: 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
timeFrame: up to 60 minute
measure: Carotid artery ultrasound examination for Aim-1 participants: backscattered and beam-steered RF data acquisition using research mode
timeFrame: up to 60 minute
measure: Fasting Lipid panel Analysis
timeFrame: up to 13 hours
measure: Hemoglobin A1C test for diabetes
timeFrame: up to 13 hours
measure: High-sensitivity C-reactive protein (HS-CRP) test for inflammatory markers for Aim 1 participants
timeFrame: up to 13 hours
measure: Detection of Plaques by MRI- Accuracy of MRI detection method as compared to Ultrasound and blood work
timeFrame: up to 60 minute
Secondary outcomes:
Other outcomes:
Locations:
city: Madison
country: United States
facility: Department of Medical Physics, University of Wisconsin
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: Tomy Varghese, PhD
role: PRINCIPAL_INVESTIGATOR
References: