Predictors of AAA Expansion and/or Rupture

Noninvasive Assessment of Abdominal Aortic Aneurysm (AAA) Wall Structural Integrity and Inflammation as Predictors of Expansion and/or Rupture

Eligible subjects in this study will have either a known abdominal aortic aneurysm (AAA) or because they do not have an AAA (control group).

The purpose of this research study is to further study, through FEA, changes that occur in the mechanical properties of the aortic wall. The investigator will compare two radiotracers, 18F-FDG and 11C-PBR28 to determine if one provides more useful and reliable information about inflammation. 18F-FDG and 11C-PBR28 are radioactive drugs that will be used for imaging during the PET-CT scan. The investigator will also compare the results describing the mechanical properties of the AAA wall to the degree of inflammation in that wall as determined by PET-CT imaging to define new and better predictors of AAA growth and/or rupture.

Study Overview

• Status: Terminated
• Conditions: Abdominal Aortic Aneurysm (AAA)
• Intervention / Treatment: Drug: Assess AAA rupture risk by PET-CTA scans; Drug: 18F-fludeoxyglucose (FDG); Diagnostic test: 11C-PBR28

Detailed Description

Eligible subjects in this study will have either a known abdominal aortic aneurysm (AAA) or because they do not have an AAA (control group).

The aorta serves as the main artery to supply blood flow to the body. It is approximately the size of a garden hose. Due to the effects of high blood pressure (hypertension), atherosclerosis (hardening of the arteries), and tobacco use, the aorta may widen and enlarge to form an aneurysm. An abdominal aortic aneurysm (AAA) is a dilation (enlargement) or ballooning out of a section of blood vessel caused by disease or weakness in the wall of the aorta below the level of the kidney arteries. As an AAA dilates and increases in size, rupture of the AAA may occur. AAA rupture carries a significant risk of death.

Currently, aortic size is the primary factor used to assess aortic rupture risk. There are other imaging procedures (imaging modalities) that are being used and developed to assess AAA rupture risk. Finite element analysis (FEA) is a way to study the mechanical properties of the aortic wall, including areas of stress and strength that are used to calculate rupture risk. Positron Emission Tomography (PET) utilizes glucose (a form of sugar) labeled with a radioactivity to look at the metabolic activity and inflammation in the aortic wall.

The purpose of this research study is to further study, through FEA, changes that occur in the mechanical properties of the aortic wall. The investigator will compare two radiotracers, 18F-FDG and 11C-PBR28 to determine if one provides more useful and reliable information about inflammation. 18F-FDG and 11C-PBR28 are radioactive drugs that will be used for imaging during the PET-CT scan. The investigator will also compare the results describing the mechanical properties of the AAA wall to the degree of inflammation in that wall as determined by PET-CT imaging to define new and better predictors of AAA growth and/or rupture.

The radioactive tracers that are used in this study are 18F-fludeoxyglucose (FDG) and 11C-PBR28 (PBR) which stands for Peripheral Benzodiazepine Receptor. 11C-PBR28 is considered investigational, which means that it has not been approved by the U.S. Food and Drug Administration. FDG is an approved drug by the FDA, however in this study it is considered investigational.

Goal: Twenty-four subjects will be recruited for this study. Six control subjects (three males and three females), will be considered. Control subjects will have known atherosclerosis, without aneurysmal disease. Six subjects (three males and three females) with small AAAs (diameter 3.0-4.5cm), six subjects (three males, AAA >5.5cm and three females, AAA >5.0cm) with AAAs that are indicated for treatment, and six subjects (three males and three females) with rapidly expanding AAAs (>0.5cm over 6 months and/or >1.0cm over 12 months) will be considered.

Subjects will have blood drawn to perform a genetic test that will look at genes and proteins to determine subject eligibility. Once the blood work is assessed for eligibility, subjects will undergo the PET-CT scan. The imaging will take approximately 3 hours to complete.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion

• All ethnic groups
• 45 years of age or older

• *Must fit into one of the three following groups:

  • Control group (atherosclerosis without aneurysmal disease
  • Small AAA (3-4.5 cm)
  • Rapidly growing AAA (0.5 cm in 6 months or 1 cm in 12 months)

Exclusion

• At risk population (cognitively impaired)
• Any exclusion for PT-CT (i.e., allergy to contrast)
• Any woman planning to become pregnant, suspects pregnancy, pregnant or breastfeeding)
• Any greater than normal potential for cardiac arrest
• Renal disease (eGFR <60 mg/ml/1.73m2)
• Claustrophobic reactions and/or is unable to lie on the exam table for 60 minutes
• Significant radiation exposure via other trials or medical testing

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Control Group; Six control subjects (three males and three females) with known atherosclerosis by standard clinical criteria without aneurysmal disease. To assess AAA rupture risk by PET-CTA scans, participants will undergo PET-CT scan using 11C-PBR28 and 18F-fludeoxyglucose (FDG) tracer. Participants will have a blood draw for genetic testing, pregnancy testing if female and creatinine testing.	Drug: Assess AAA rupture risk by PET-CTA scans; Assess AAA rupture risk by PET-CTA scans; Drug: 18F-fludeoxyglucose (FDG); Assess AAA rupture risk by PET-CTA scans using 18F-fludeoxyglucose (FDG)and 11C-PBR28 PET-CT and contrast-enhanced CTA imaging; Other Names: 18F-FDG; Diagnostic test: 11C-PBR28; Assess AAA rupture risk by PET-CTA scans using 18F-fludeoxyglucose (FDG)and 11C-PBR28 PET-CT and contrast-enhanced CTA imaging
Other: Small AAA's; Six subjects (three males and three females) with small AAAs (diameter 3.0-4.5cm). To assess AAA rupture risk by PET-CTA scans, participants will undergo PET-CT scan using 11C-PBR28 and 18F-fludeoxyglucose (FDG) tracer. Participants will have a blood draw for genetic testing, pregnancy testing if female and creatinine testing.	Drug: Assess AAA rupture risk by PET-CTA scans; Assess AAA rupture risk by PET-CTA scans; Drug: 18F-fludeoxyglucose (FDG); Assess AAA rupture risk by PET-CTA scans using 18F-fludeoxyglucose (FDG)and 11C-PBR28 PET-CT and contrast-enhanced CTA imaging; Other Names: 18F-FDG; Diagnostic test: 11C-PBR28; Assess AAA rupture risk by PET-CTA scans using 18F-fludeoxyglucose (FDG)and 11C-PBR28 PET-CT and contrast-enhanced CTA imaging
Other: Rapidly expanding AAA's; Six subjects (three males and three females) with rapidly expanding AAAs (>0.5cm over 6 months and/or >1.0cm over 12 months). To assess AAA rupture risk by PET-CTA scans, participants will undergo PET-CT scan using 11C-PBR28 and 18F-fludeoxyglucose (FDG) tracer. Participants will have a blood draw for genetic testing, pregnancy testing if female and creatinine testing.	Drug: Assess AAA rupture risk by PET-CTA scans; Assess AAA rupture risk by PET-CTA scans; Drug: 18F-fludeoxyglucose (FDG); Assess AAA rupture risk by PET-CTA scans using 18F-fludeoxyglucose (FDG)and 11C-PBR28 PET-CT and contrast-enhanced CTA imaging; Other Names: 18F-FDG; Diagnostic test: 11C-PBR28; Assess AAA rupture risk by PET-CTA scans using 18F-fludeoxyglucose (FDG)and 11C-PBR28 PET-CT and contrast-enhanced CTA imaging
Other: AAA's undergoing treatment; Six subjects (three males, AAA >5.5cm and three females, AAA >5.0cm) with AAAs that are indicated for treatment. To assess AAA rupture risk by PET-CTA scans, participants will undergo PET-CT scan using 11C-PBR28 and 18F-fludeoxyglucose (FDG) tracer. Participants will have a blood draw for genetic testing, pregnancy testing if female and creatinine testing.	Drug: Assess AAA rupture risk by PET-CTA scans; Assess AAA rupture risk by PET-CTA scans; Drug: 18F-fludeoxyglucose (FDG); Assess AAA rupture risk by PET-CTA scans using 18F-fludeoxyglucose (FDG)and 11C-PBR28 PET-CT and contrast-enhanced CTA imaging; Other Names: 18F-FDG; Diagnostic test: 11C-PBR28; Assess AAA rupture risk by PET-CTA scans using 18F-fludeoxyglucose (FDG)and 11C-PBR28 PET-CT and contrast-enhanced CTA imaging

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Standard Uptake Value (SUV)	Aortic inflammation as demonstrated by uptake of radiotracer	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rupture Potential Index (RPI)	Rupture potential index (RPI) is defined as the ratio of the acting wall stress to the wall strength, and the maximum RPI for AAA represents its rupture risk. Currently, the primary factor considered for risk of human AAA rupture is aortic diameter; however, it is well documented that small AAAs (<5cm) rupture, while many large AAAs (>8cm) are incidentally discovered. We will assess the ability of imaging techniques to determine abdominal aortic aneurysm (AAA) rupture risk individually and in concert.	9-10 months
Qualitative Comparison of SUV and RPI	Finite element analysis (FEA) is a computerized numerical method used for the prediction of how the aorta may behave under stress. This software will be used to assess the same aortic volume comparing areas of greatest stress and lowest strength. Co-registration of images obtained by different imaging modalities will allow for comparison between imaging modalities. With direct co-registration of the data sets for each subject, qualitative comparisons will be made regarding areas of 18F-FDG and 11C-PBR28 uptake, as well as stress, strength, and RPI.	9-10 months

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Investigators: Principal Investigator: Sean J. English, MD, Washington University School of Medicine, St. Louis, MO 63110

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2017
• Primary Completion (Actual): April 30, 2020
• Study Completion (Actual): April 30, 2020

Study Registration Dates

• First Submitted: June 22, 2017
• First Submitted That Met QC Criteria: July 25, 2017
• First Posted (Actual): July 27, 2017

Study Record Updates

• Last Update Posted (Actual): July 9, 2021
• Last Update Submitted That Met QC Criteria: June 17, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Abdominal Aortic Aneurysm (AAA)
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Wounds and Injuries; Aortic Diseases; Rupture; Aneurysm; Aortic Aneurysm; Aortic Aneurysm, Abdominal; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Fluorodeoxyglucose F18
• Other Study ID Numbers: 201702141

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No