Neuroinflammation in Asymptomatic Carotid Artery Disease - Imaging Substudy

Study Overview
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Brief Summary
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This clinical imaging substudy will use the small molecule translocator protein (TSPO) ligand, Fludeoxyglucose(18F)-labeled DPA-714, to compare neuroinflammation in individuals with high or low grade asymptomatic carotid artery stenosis (aCAD) who are participating in the separate Neuroinflammation in Asymptomatic Carotid Artery Disease study lead by Dr. Ron Lazar (IRB-300007806). The positron emission tomography (PET) tracer [18F]DPA-714 binds to the 18 kDa translocator protein (TSPO, also known as the peripheral benzodiazepine receptor) in the mitochondria of activated microglia/macrophages and provides a non-invasive measure of neuroinflammation.

Official Title
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Neuroinflammation in Asymptomatic Carotid Artery Disease - Imaging Substudy

Conditions
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Critical Asymptomatic Carotid Artery Disease, Non-Critical Asymptomatic Carotid Artery Disease

Intervention / Treatment
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* Drug: [18F]DPA-714


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cohort 1 - Critical Asymptomatic Carotid Stenosis Group Inclusion Criteria: Critical Stenosis Group: Diagnosis of Asymptomatic Carotid Artery Disease (aCAD) with >70% stenosis or peak systolic velocity on DUS ≥ 230 cm/s plus CTA or MRA confirmation. Participation in University of Alabama at Birmingham (UAB) IRB protocol Neuroinflammation in Asymptomatic Carotid Artery Disease (IRB-300007806, PI Lazar). Male or female age >18 years English speaking with at least 8th grade education High affinity binder for TSPO ligands based on genotyping for single nucleotide polymorphism (SNP) rs6971 Planned revascularization for aCAD in >14 days from time of consent Cohort 2 - Non-Critical Asymptomatic Carotid Stenosis Group Inclusion Criteria: Participation in UAB IRB protocol Neuroinflammation in Asymptomatic Carotid Artery Disease (IRB-300007806, PI Lazar). <40% carotid stenosis No planned revascularization Male or female age 18 or older English speaking with at least 8th grade education High affinity binder for TSPO ligands based on genotyping SNP rs6971 Exclusion Criteria: Contraindication to MRI Pregnancy or lactation Previous revascularization for treatment of aCAD Prior stroke Severe anemia (blood hemoglobin ≤ 8 mg/dL) Previously obtained MRI scan with evidence of clinically significant abnormality History of traumatic head injury defined by loss of consciousness >30 minutes or seizure at the time of the injury Major depression Known history of dementia Serious medical comorbidity that, based on the judgement of the principal investigator, may interfere with study participation Low or mixed-affinity binding for TSPO ligands based on genotyping for SNP rs6971.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 - Critical Asymptomatic Carotid Stenosis Group<br>Critical Stenosis Group: Diagnosis of Asymptomatic Carotid Artery Disease (aCAD) with >70% stenosis or peak systolic velocity on duplex ultrasound (DUS) ≥ 230 cm/s plus computed tomography angiography (CTA) or magnetic resonance angiography (MRA) confirmation. | Drug: [18F]DPA-714<br>* Investigational PET Tracer [18F]DPA-714<br>|
| Experimental: Cohort 2 - Controls-Non-Critical Asymptomatic Carotid Stenosis Group<br><40% carotid stenosis No planned revascularization | Drug: [18F]DPA-714<br>* Investigational PET Tracer [18F]DPA-714<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total volume distribution of the regional time-activity curves from the TSPO- PET Data. | The regional time-activity curves from the TSPO-PET data will be combined with image derived input function to provide estimates of total volume distribution (VT) based on a 2-tissue-compartment model (2-TCM) and graphical Logan plot analysis. | Pre-study to 48 hours post PET imaging. |