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

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ClinicalTrials.gov Identifier: NCT03068442
Recruitment Status : Recruiting
First Posted : March 1, 2017
Last Update Posted : May 3, 2018
Sponsor:
Collaborator:
American Heart Association
Information provided by (Responsible Party):
Scott Mcnally, University of Utah

Brief 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.

Condition or disease Intervention/treatment Phase
Cognitive Impairment Carotid Artery Plaque Inflammation Drug: Imaging with flutemetamol F 18 PET/CT Phase 2

Detailed 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Intervention Model: Single Group Assignment
Intervention Model Description: This is a diagnostic-interventional cohort study in patients undergoing carotid endarterectomy for atherosclerotic disease.
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Amyloid Deposition and Preexisting Vulnerable Carotid Plaque Features Predicting Cognitive Improvement After Surgery
Actual Study Start Date : February 17, 2017
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : December 31, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Carotid atherosclerosis group
This group includes all enrolled subjects (those with carotid disease and plans to undergo surgery).
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




Primary Outcome Measures :
  1. Carotid intraplaque hemorrhage correlation with carotid plaque inflammation on immunohistochemistry. [ Time Frame: baseline ]
    Carotid plaque inflammation will be calculated with quantitative immunohistochemistry and correlated with intraplaque hemorrhage while controlling for confounders.

  2. Carotid MRI-detected intraplaque hemorrhage and prediction of brain inflammation on PET/CT. [ Time Frame: baseline ]
    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.

  3. Preoperative MRI-detected carotid intraplaque hemorrhage and prediction of cognitive improvement after endarterectomy. [ Time Frame: Change from baseline at 3 month followup ]
    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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03068442


Contacts
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Contact: Collin Arsenault 801-585-1737 Collin.Arsenault@hsc.utah.edu
Contact: Suyi Nui 801-585-1021 SUYI.NIU@hsc.utah.edu

Locations
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United States, Utah
University of Utah Recruiting
Salt Lake City, Utah, United States, 84132
Contact: Collin Arsenault    801-585-1737    Collin.Arsenault@hsc.utah.edu   
Contact: Suyi Nui    801-585-1021    SUYI.NIU@hsc.utah.edu   
Principal Investigator: Joseph S McNally, MD, PhD         
George E. Wahlen Department of Veterans Affairs Medical Center Recruiting
Salt Lake City, Utah, United States, 84148
Contact: Collin Arsenault    801-585-1737    Collin.Arsenault@hsc.utah.edu   
Contact: Suyi Nui    801-585-1021    SUYI.NIU@hsc.utah.edu   
Principal Investigator: Joseph S McNally, MD, PhD         
Sponsors and Collaborators
Scott Mcnally
American Heart Association
Investigators
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Principal Investigator: Joseph S McNally, MD, PhD University of Utah

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Responsible Party: Scott Mcnally, Assistant Professor, Department of Radiology, University of Utah
ClinicalTrials.gov Identifier: NCT03068442     History of Changes
Other Study ID Numbers: 17SDG33460420
First Posted: March 1, 2017    Key Record Dates
Last Update Posted: May 3, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

All data will be made freely and publicly available on ClinicalTrials.gov within 12 months of the end of the funding period (and any no-cost extension).

  1. Carotid intraplaque hemorrhage
  2. Carotid plaque inflammation on histology
  3. Age, stroke status, male sex, smoking and vitamin D level
  4. Statin, antiplatelet, or antihypertensive use
  5. Ipsilateral brain inflammation measured by PET
  6. Carotid stenosis and perfusion parameters
  7. Cognitive score

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Scott Mcnally, University of Utah:
Carotid artery
MRI
PET
Intraplaque hemorrhage

Additional relevant MeSH terms:
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Carotid Stenosis
Inflammation
Cognitive Dysfunction
Pathologic Processes
Cognition Disorders
Neurocognitive Disorders
Mental Disorders
Carotid Artery Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Flutemetamol
Radiopharmaceuticals
Molecular Mechanisms of Pharmacological Action