Neuroinflammation in Asymptomatic Carotid Artery Disease - Imaging Substudy

• Sponsor: University of Alabama at Birmingham (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05238961
• Collaborator: (none)
• Enrollment: 20
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 41
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Critical Asymptomatic Carotid Artery Disease; Non-Critical Asymptomatic Carotid Artery Disease	Drug: [18F]DPA-714	Phase 1

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 20 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Neuroinflammation in Asymptomatic Carotid Artery Disease - Imaging Substudy
• Anticipated Study Start Date: Aug 1, 2022
• Anticipated Primary Completion Date: Dec 31, 2024
• Anticipated Study Completion Date: Dec 31, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 - Critical Asymptomatic Carotid Stenosis Group 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; Investigational PET Tracer [18F]DPA-714
Experimental: Cohort 2 - Controls-Non-Critical Asymptomatic Carotid Stenosis Group <40% carotid stenosis No planned revascularization	Drug: [18F]DPA-714; Investigational PET Tracer [18F]DPA-714

Outcome Measures

Primary Outcome Measures

1. Total volume distribution of the regional time-activity curves from the TSPO- PET Data. [Pre-study to 48 hours post PET imaging.]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

1. Participation in University of Alabama at Birmingham (UAB) IRB protocol "Neuroinflammation in Asymptomatic Carotid Artery Disease" (IRB-300007806, PI Lazar).

2. Male or female age >18 years

3. English speaking with at least 8th grade education

4. High affinity binder for TSPO ligands based on genotyping for single nucleotide polymorphism (SNP) rs6971

5. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UAB	Birmingham	Alabama	United States	35294

Sponsors and Collaborators

• University of Alabama at Birmingham

Investigators

• Principal Investigator: Jonathan McConathy, MD,PhD, University of Alabama at Birmingham

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jonathan E McConathy, Official Title: M.D. P.h.D., Director for the Division Molecular Imaging and Therapeutics Affiliation: University of Alabama at Birmingham, University of Alabama at Birmingham
• ClinicalTrials.gov Identifier: NCT05238961
• Other Study ID Numbers: R22-019
• First Posted: Feb 14, 2022
• Last Update Posted: Jun 30, 2022
• Last Verified: Jun 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Carotid Artery Diseases

Study Results

No Results Posted as of Jun 30, 2022