Clinical trial NCT04592991: CCR2 AAA Pilot Study
Official title: Targeted Molecular Probe for Abdominal Aortic Aneurysm Imaging and Therapy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: EARLY_PHASE1
Conditions: Abdominal Aortic Aneurysm (AAA)
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2020-10-19
Enrollment: 1
Sex: ALL
Minimum age (years): 45
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: There will be two (2) groups in this study. We plan to recruit 5 patients with AAA and 3 patients with diagnosed non-aneurysmal (without aneurysm) aortoiliac occlusive disease.
Primary purpose: DIAGNOSTIC

Brief summary: The purpose of this research study is to look at whether an investigational imaging agent, 64Cu-DOTA-ECL1i, used during Positron Emission Tomography (PET)/ Computed Tomography (CT) scanning, can help to identify conditions that place patients at an increased risk for AAA rupture. The study is also looking more closely at cellular, molecular and inflammatory properties of the aortic wall. Having the ability to identify markers that predict AAA progression/expansion and risk for rupture could allow the physician to manage patients in a more individualized, personal way.

Detailed description: Abdominal aortic aneurysm (AAA) is a life-threatening degenerative vascular disease characterized by transmural aortic macrophage infiltration, elastin degradation, and reduction of smooth muscle cell content. AAAs occurs later in life and are especially prevalent in men over the age of 65. Patients typically remain asymptomatic until rupture, which is associated with high mortality. Currently, surgical repair is the only approach for AAA treatment, and there is no pharmacological intervention. Clinically, ultrasound and computed tomography measurement of aneurysm diameter represents the mainstay of management and the principal determinant of timing for elective surgical repair. However, this anatomy-based approach fails to provide useful information about the cellular and molecular processes associated with aneurysm expansion and rupture. Therefore, developing translatable molecular biomarkers, specifically expressed by aneurysms, is necessary to determine associated status and progression, capture the risk of rupture, and deliver personalized treatment.

Eligibility criteria: Non-Aneurysmal Patients, (Aim 2A, n=3)

Inclusion Criteria:

- Patients with aortoiliac occlusive disease causing lifestyle limiting claudication, rest pain, and/or tissue loss that requires aortofemoral bypass

Exclusion Criteria:

- Patients with aortoiliac occlusive disease, we will apply the same exclusion criteria as AAA patients.

Abdominal Aortic Aneurysm (AAA) Patients, (Aim 2B, n=5)

Inclusion Criteria:

* We will recruit asymptomatic patients with known AAAs by ultrasound, Doppler, and CT (men ≥ 5.5 cm, women ≥ 5.0cm);
* Both men and women, between the ages of 45 -75;
* With or without active tobacco use;

Exclusion Criteria:

* Inability to receive and sign informed consent;
* Has a history of hypersensitivity to contrast agent, Iopamidol (Isovue)
* Patients with Stage ≥ 4 chronic renal failure (calculated by modification of diet in renal disease eGFR equation \[to minimize confounding imaging variables\]);
* Inability to tolerate 60 minutes in a supine position with arms down at sides, as necessary for PET/CT;
* Severe claustrophobia;
* Positive pregnancy test or lactating;
* Has a history of hypersensitivity to 64Cu-DOTA-ECL1i or any of its excipients;
* Any condition that, in the opinion of the Sponsor-Investigator or designee could increase risk to the participant, limit the participant's ability to tolerate the research procedures or interfere with collection of the data such as: Symptomatic/recently treated coronary disease, cancer requiring oncologic management, or autoimmune/inflammatory diseases (e.g., rheumatoid arthritis or multiple sclerosis) that are known to have increased associated expression of CCR2.

Primary outcomes:
measure: First in-person CCR2 molecular imaging using 64Cu-DOTA-ECL1i PET/CT in AAA patient
timeFrame: 1-2 weeks
measure: Perform 64Cu-DOTA-ECL1i PET/CT in AAA patients and correlate imaging readouts with tissue inflammatory biomarkers in patients undergoing open repair
timeFrame: 1-2 weeks prior to surgery
Secondary outcomes:
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Mohamed M. Zayed, MD
role: PRINCIPAL_INVESTIGATOR
References: