Abdominal Aortic Aneurysm
Conditions
Brief summary
The goal is to non-invasively study the metabolic processes within the aortic wall that are thought to explain progression to clinical manifestations of an aortic aneurysm. Hypothesis is that the non-invasive imaging of Abdominal Aortic Aneurysm (AAA) with contrast ultrasound, coupled with serum biomarker measurements will allow the identification of the vulnerable aortic wall and patients who are at risk of AAA growth or rupture.
Detailed description
Aim#1: Prospective Contrast Ultrasound (CUS) imaging of patients with AAA to predict AAA growth and test gender differences in rate of growth and rupture. Aim#2: Serum biomarker testing of patient with AAA. CUS findings will be correlated with serum biomarkers and AAA wall histology. Prospective Contrast Ultrasound imaging of patients with AAA as part of a pilot feasibility study to predict AAA growth and test gender differences in rate of growth and rupture. CUS findings will be correlated with serum biomarkers and AAA wall histology. Potential significance: This study will evaluate the AAA wall and will be based on detecting areas of increased vasa vasorum density within the aneurysm wall and intraluminal thrombus, which indicate regional ischemia and inflammation of the aortic wall and propensity for weakening, enlargement or rupture. This novel evaluation of the aortic wall in patients with AAA will allow individualized treatment based on the biological potential for growth and rupture.
Interventions
Definity® is the contrast agent that will be administered by intravenous injection by a registered nurse during the ultrasound (contrast enhanced ultrasound (CUS). The purpose is to assist in identifying differences in AAA characteristics based on gender and AAA stability and growth.
Sponsors
National Institute on Aging (NIA)
Rabih A. Chaer
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Diagnosis of AAA with confirmation of diagnosis of any size aneurysm with imaging. * 21 years of age or older * ability to give informed consent.
Exclusion criteria
* Inability to provide an informed consent * Known allergy to Definity * Unstable cardiopulmonary conditions * pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Annual Aneurysm Growth Rate Between Patients With and Without Micro Bubble Uptake | Up to 5 years or time of aneurysm repair surgery. | Prospective contrast ultrasound will be performed at regular clinically indicated timepoints. |
| Number of Participants With Microbubble Uptake | At the first follow-up evaluation at 6 months | Microbubble uptake was determined on ultrasound evaluation of the abdominal aorta. This was agreed upon by two reading physicians. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Value of Systemic Inflammatory Serum Biomarkers | baseline, 6 months | Systemic serum biomarkers of AAA will be measured. These markers are circulating levels of C Reactive Protein, cytokines and osteoprotegerin. Serum markers will be drawn at baseline and at the next follow-up visit which is 6 months after the index visit. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Contrast Ultrasound for Patients With AAA Contrast ultrasound
contrast ultrasound: Definity® is the contrast agent that will be administered by intravenous injection by a registered nurse during the ultrasound (contrast enhanced ultrasound (CUS). The purpose is to assist in identifying differences in AAA characteristics based on gender and AAA stability and growth.
Contrast Ultrasound: Definity® is the contrast agent that will be administered by intravenous injection by a registered nurse during the ultrasound (contrast enhanced ultrasound (CUS). The purpose is to assist in identifying differences in AAA characteristics based on gender and AAA stability and growth. | 59 |
| Contrast Ultrasound for Patients Without Arterial Disease contrast enhanced ultrasound
contrast ultrasound: Definity® is the contrast agent that will be administered by intravenous injection by a registered nurse during the ultrasound (contrast enhanced ultrasound (CUS). The purpose is to assist in identifying differences in AAA characteristics based on gender and AAA stability and growth.
Contrast Ultrasound: Definity® is the contrast agent that will be administered by intravenous injection by a registered nurse during the ultrasound (contrast enhanced ultrasound (CUS). The purpose is to assist in identifying differences in AAA characteristics based on gender and AAA stability and growth. | 7 |
| Total | 66 |
Baseline characteristics
| Characteristic | Contrast Ultrasound for Patients Without Arterial Disease | Total | Contrast Ultrasound for Patients With AAA |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 42 Participants | 41 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 24 Participants | 18 Participants |
| Age, Continuous | 49.4 years STANDARD_DEVIATION 12.8 | 67.3 years STANDARD_DEVIATION 10.3 | 68.8 years STANDARD_DEVIATION 8.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 5 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 59 Participants | 55 Participants |
| Region of Enrollment United States | 7 participants | 66 participants | 59 participants |
| Sex: Female, Male Female | 6 Participants | 14 Participants | 8 Participants |
| Sex: Female, Male Male | 1 Participants | 52 Participants | 51 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 59 | 0 / 7 |
| other Total, other adverse events | 0 / 59 | 0 / 7 |
| serious Total, serious adverse events | 0 / 59 | 0 / 7 |
Outcome results
Primary
Annual Aneurysm Growth Rate Between Patients With and Without Micro Bubble Uptake
Prospective contrast ultrasound will be performed at regular clinically indicated timepoints.
Time frame: Up to 5 years or time of aneurysm repair surgery.
Population: Annual aneurysm growth rate only relevant for patients with aneurysm disease
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Contrast Ultrasound for Patients With Aneurysm Disease | Annual Aneurysm Growth Rate Between Patients With and Without Micro Bubble Uptake | Microbubble Uptake | 3.0 mm/year | Standard Deviation 3.1 |
| Contrast Ultrasound for Patients With Aneurysm Disease | Annual Aneurysm Growth Rate Between Patients With and Without Micro Bubble Uptake | No Microbubble Uptake | 3.2 mm/year | Standard Deviation 3.1 |
Primary
Number of Participants With Microbubble Uptake
Microbubble uptake was determined on ultrasound evaluation of the abdominal aorta. This was agreed upon by two reading physicians.
Time frame: At the first follow-up evaluation at 6 months
Population: Microbubble Uptake was only evaluated in patients with aneurysm disease as patients without aneurysm disease do not have micro bubble uptake.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Contrast Ultrasound for Patients With Aneurysm Disease | Number of Participants With Microbubble Uptake | 36 Participants |
Secondary
Mean Value of Systemic Inflammatory Serum Biomarkers
Systemic serum biomarkers of AAA will be measured. These markers are circulating levels of C Reactive Protein, cytokines and osteoprotegerin. Serum markers will be drawn at baseline and at the next follow-up visit which is 6 months after the index visit.
Time frame: baseline, 6 months
Population: For patients without arterial disease, serum biomarkers were only obtained at baseline; no follow-up visits occurred and therefore no further biomarker testing was done.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Contrast Ultrasound for Patients With Aneurysm Disease | Mean Value of Systemic Inflammatory Serum Biomarkers | C Reactive Protein (at 6 months) | 7808.0 pg/ml |
| Contrast Ultrasound for Patients With Aneurysm Disease | Mean Value of Systemic Inflammatory Serum Biomarkers | Interferon (at 6 months) | 5.1 pg/ml |
| Contrast Ultrasound for Patients With Aneurysm Disease | Mean Value of Systemic Inflammatory Serum Biomarkers | Osteoprotegrin | 225.5 pg/ml |
| Contrast Ultrasound for Patients With Aneurysm Disease | Mean Value of Systemic Inflammatory Serum Biomarkers | Interferon | 4.2 pg/ml |
| Contrast Ultrasound for Patients With Aneurysm Disease | Mean Value of Systemic Inflammatory Serum Biomarkers | C Reactive Protein | 7090.3 pg/ml |
| Contrast Ultrasound for Patients With Aneurysm Disease | Mean Value of Systemic Inflammatory Serum Biomarkers | Osteoprotegrin (at 6 months) | 257.4 pg/ml |
| Contrast Ultrasound for Patients Without Arterial Disease | Mean Value of Systemic Inflammatory Serum Biomarkers | Interferon | 2.4 pg/ml |
| Contrast Ultrasound for Patients Without Arterial Disease | Mean Value of Systemic Inflammatory Serum Biomarkers | C Reactive Protein | 1843.0 pg/ml |
| Contrast Ultrasound for Patients Without Arterial Disease | Mean Value of Systemic Inflammatory Serum Biomarkers | Osteoprotegrin | 214.8 pg/ml |