Neuroinflammation in Asymptomatic Carotid Artery Disease - Imaging Substudy

The University of Alabama at Birmingham

Status and phase: Enrolling; Phase 1

Conditions: Critical Asymptomatic Carotid Artery Disease; Non-Critical Asymptomatic Carotid Artery Disease

Treatments: Drug: [18F]DPA-714

Study type: Interventional

Funder types: Other

Identifiers

NCT05238961

R22-019

Details and patient eligibility

About

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.

Enrollment: 20 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Cohort 1 - Critical Asymptomatic Carotid Stenosis Group Inclusion Criteria:

1. 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.
2. Participation in University of Alabama at Birmingham (UAB) IRB protocol "Neuroinflammation in Asymptomatic Carotid Artery Disease" (IRB-300007806, PI Lazar).
3. Male or female age >18 years
4. English speaking with at least 8th grade education
5. High affinity binder for TSPO ligands based on genotyping for single nucleotide polymorphism (SNP) rs6971
6. Planned revascularization for aCAD in >14 days from time of consent

Cohort 2 - Non-Critical Asymptomatic Carotid Stenosis Group Inclusion Criteria:

1. Participation in UAB IRB protocol "Neuroinflammation in Asymptomatic Carotid Artery Disease" (IRB-300007806, PI Lazar).
2. <40% carotid stenosis
3. No planned revascularization
4. Male or female age 18 or older
5. English speaking with at least 8th grade education
6. High affinity binder for TSPO ligands based on genotyping SNP rs6971

Exclusion criteria

1. Contraindication to MRI
2. Pregnancy or lactation
3. Previous revascularization for treatment of aCAD
4. Prior stroke
5. Severe anemia (blood hemoglobin ≤ 8 mg/dL)
6. Previously obtained MRI scan with evidence of clinically significant abnormality
7. History of traumatic head injury defined by loss of consciousness >30 minutes or seizure at the time of the injury
8. Major depression
9. Known history of dementia
10. Serious medical comorbidity that, based on the judgement of the principal investigator, may interfere with study participation
11. Low or mixed-affinity binding for TSPO ligands based on genotyping for SNP rs6971.

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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20 participants in 2 patient groups

Cohort 1 - Critical Asymptomatic Carotid Stenosis Group

Experimental group

Description:

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.

Treatment:

Drug: [18F]DPA-714

Cohort 2 - Controls-Non-Critical Asymptomatic Carotid Stenosis Group

Experimental group

Description:

\<40% carotid stenosis No planned revascularization

Treatment:

Drug: [18F]DPA-714