CCR2 AAA Pilot Study

NCT04592991 | Terminated Early Phase 1 DMC FDA Drug

• 1 other identifier: 202004104
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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.

Conditions

Abdominal Aortic Aneurysm (AAA)

Outcome Measures

Primary Outcomes (2)

• First in-person CCR2 molecular imaging using 64Cu-DOTA-ECL1i PET/CT in AAA patient

  Determine the background retention of 64Cu-DOTA-ECL1i in the abdominal aorta of patients with non-aneurysmal, atherosclerotic occlusive disease.

  1-2 weeks

• Perform 64Cu-DOTA-ECL1i PET/CT in AAA patients and correlate imaging readouts with tissue inflammatory biomarkers in patients undergoing open repair

  Patients undergoing open AAA repair will be scheduled for PET/CT imaging at 1-2 weeks prior to surgery. This will be first-in-patient molecular imaging using CCR2 targeted 64Cu-DOTA-ECL1i in AAA patients undergoing open repair. The surgically removed aneurysmal tissue will be collected and processed for a complete characterization.

  1-2 weeks prior to surgery

Study Arms (2)

AAA Group

ACTIVE COMPARATOR

Participants with AAA will undergo routine clinical evaluation of AAA including ultrasound and CT and scheduling of open surgical repair as directed by the treating physician. We will record age and tobacco use of participant. If participant has not had a renal function blood test performed within the past 90 days, we will draw approximately 2 teaspoons of blood for a creatinine test. We will also ask the participant's permission to use a contrast dye for the CT portion of the PET-CT scan. If the participant agrees we will additional questions to gauge eligibility to receive the contrast dye. If available, we would like to collect any discarded AAA tissue from the surgical procedure. This discarded tissue will be kept as part of a Washington University vascular research repository. If the participant agrees to this there will be a separate consent form to sign allowing the collection of the leftover tissue along with some information about medical history.

Diagnostic Test: AAA Group- PET-CT imaging with injection of 64Cu-DOTA-ECL1i

Aortoiliac Occlusive Disease Group

ACTIVE COMPARATOR

Participants with non-aneurysmal aortoiliac occlusive disease, will be eligible for the study based on lifestyle limiting claudication (lack of blood flow to muscles causing cramping), pain in the feet or toes at rest, and/or tissue loss (leg or foot ulcers that don't heal or gangrene) that requires aortofemoral bypass. The aortofemoral bypass is not part of this research study.

Diagnostic Test: Aortoiliac Occlusive Disease Group - PET-CT imaging with injection of 64Cu-DOTA-ECL1i

Interventions

Aortoiliac Occlusive Disease Group - PET-CT imaging with injection of 64Cu-DOTA-ECL1i DIAGNOSTIC_TEST

Patients from both genders, all ethnic groups, and between the ages of 45 and 75 will be considered for recruitment. We will recruit patients who have evidence of abdominal aortic aneurysm (AAA) as our study patient cohort. Patients with non-aneurysmal, atherosclerotic aortoiliac occlusive disease (n=3) will be enrolled in Aim 2A and undergo Cu-64 DOTA-ECL1i PET/CT.

Aortoiliac Occlusive Disease Group

AAA Group- PET-CT imaging with injection of 64Cu-DOTA-ECL1i DIAGNOSTIC_TEST

Patients from both genders, all ethnic groups, and between the ages of 45 and 75 will be considered for recruitment. We will recruit patients who have evidence of abdominal aortic aneurysm (AAA) as our study patient cohort. Patients with Abdominal aortic aneurysm (AAA) (n=5) will be enrolled in Aim 2B and undergo Cu-64 DOTA-ECL1i PET/CT and contrast-enhanced CT angiography between 7-14 days of their scheduled elective open repair surgery.

AAA Group

Eligibility Criteria

• Age: 45 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

MeSH Terms

Conditions

Aortic Aneurysm, Abdominal

Condition Hierarchy (Ancestors)

Aortic Aneurysm; Aneurysm; Vascular Diseases; Cardiovascular Diseases; Aortic Diseases

Study Officials

• Mohamed M. Zayed, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: October 5, 2020
• First Posted: October 19, 2020
• Study Start: October 7, 2020
• Primary Completion: April 4, 2022
• Study Completion: April 4, 2022
• Last Updated: April 15, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)