The Role of Large Artery Plaque Imaging Features in Predicting Inflammation and Cognition

Inflammation Clinical Trial

Official title:

Amyloid Deposition and Preexisting Vulnerable Carotid Plaque Features Predicting Cognitive Improvement After Surgery

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03068442
• Other study ID #: 17SDG33460420
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: February 17, 2017
• Est. completion date: September 10, 2024

Study information

• Verified date: January 2024
• Source: University of Utah
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The invesigators propose a clinical study on patients undergoing carotid surgery (endarterectomy). The invesigators will determine carotid artery imaging features associated with (1) vessel wall inflammation, (2) downstream brain inflammation, and (3) cognitive benefit from surgery. This project will uncover links between inflamed carotid plaque and downstream brain inflammation. The invesigators will also determine carotid plaque imaging features predicting cognitive benefit from carotid surgery.

Description:

This research is directed at a major stroke source, the carotid artery, a major vessel that supplies blood to the brain. It has long been known that carotid narrowing is an important stroke risk factor. However, many patients with narrow carotids do not have strokes, and many patients with seemingly normal carotids have strokes. MRI research now suggests that the carotid wall itself is the stroke source. Using carotid MRI, clinicians can identify previously invisible markers of unstable carotid plaque, including carotid wall bleeds (intraplaque hemorrhage). The working hypothesis is that patients with these unstable carotid plaques may have higher inflammation in both their carotid arteries and brain. This inflammation has been implicated in other diseases, including dementia.

Carotid wall bleeds can easily be seen with carotid MRI, but are often invisible on ultrasound and CT scans. By using MRI, the invesigators have found that this silent killer is an important stroke risk factor even without carotid narrowing. Now that imaging can detect carotid wall bleeds, where do the bleeds come from? Recent research points to inflammation within the carotid wall. The invesigators plan to use histology to detect this inflammation in the vessel wall. Another question is, does inflammation in the carotid wall lead to inflammation in the brain? Using PET scans, the invesigators plan to determine whether inflammation in the brain is linked to carotid disease. Lastly, the invesigators hope to find out if carotid wall inflammation contributes to memory loss and if surgery is beneficial in these patients.

The invesigators hope to detect this inflammation in the vessel wall and brain before patients develop stroke, memory loss and dementia. This will be of huge benefit not only in the detection of diseases, but would also allow clinicians to monitor treatment effect on both carotid disease and brain inflammation. The invesigators also hope to use these tools to detect early treatment response. This research will accelerate the pace of future clinical trials to bring important new medications to patients sooner.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 45
• Est. completion date: September 10, 2024
• Est. primary completion date: September 10, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients =18 years old and plans for carotid endarterectomy.

Exclusion Criteria:

• Patients with carotid occlusion will be excluded, due to one carotid contributing to both right and left brain blood supply.

• Other known sources of cardioembolism, including atrial fibrillation, mechanical heart valve, left atrial or ventricular thrombus or intracardiac mass, endocarditis, EF <30%

• Known stroke mimics including multiple sclerosis or brain tumor

• MRI contraindications per ACR guidelines, including patients with pacemakers, renal failure with eGFR<30 ml/min/1.73m2, and contrast allergy

• [18F]Flutemetamol contraindications per manufacturer guidelines, including patients with prior reactions

• Known stage IV malignancy

• Pregnancy

Related Conditions & MeSH terms

• Carotid Artery Plaque
• Carotid Stenosis
• Cognitive Impairment
• Inflammation

Intervention

Drug:
• Imaging with flutemetamol F 18 PET/CT
All subjects will undergo diagnostic imaging as the intervention. This imaging will be with flutemetamol F 18 PET/CT

Locations

Country	Name	City	State
United States	George E. Wahlen Department of Veterans Affairs Medical Center	Salt Lake City	Utah
United States	University of Utah	Salt Lake City	Utah

Sponsors (2)

Lead Sponsor	Collaborator
Scott Mcnally	American Heart Association

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Carotid intraplaque hemorrhage correlation with carotid plaque inflammation on immunohistochemistry.	Carotid plaque inflammation will be calculated with quantitative immunohistochemistry and correlated with intraplaque hemorrhage while controlling for confounders.	baseline
Primary	Carotid MRI-detected intraplaque hemorrhage and prediction of brain inflammation on PET/CT.	Outcome 2. The primary outcome, brain inflammation will be compared in carotid intraplaque hemorrhage positive and negative sides, controlling for confounders including stenosis and perfusion.	baseline
Primary	Preoperative MRI-detected carotid intraplaque hemorrhage and prediction of cognitive improvement after endarterectomy.	Outcome 3. The primary outcome, difference in cognitive score will be compared in carotid intraplaque hemorrhage positive and negative patients, controlling for stenosis, perfusion and ischemic symptoms.	Change from baseline at 3 month followup