Ignite Creation Date:
2024-05-06 @ 3:18 PM
Last Modification Date:
2024-10-26 @ 1:46 PM
Study NCT ID:
NCT04586452
Status:
RECRUITING
Last Update Posted:
2023-07-18
First Post:
2020-09-29
Brief Title:
NIH CCR2 AAA Study
Sponsor:
Washington University School of Medicine
Organization:
Washington University School of Medicine
Study Overview
Official Title:
CCR2 Targeted Molecular Imaging and Treatment of Abdominal Aortic Aneurysms
Status:
RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Abdominal aortic aneurysm AAA is a degenerative vascular disease which is typically asymptomatic until rupture resulting in high mortality AAAs are more prevalent in men over age 65 though rupture is disproportionately higher in women Due to nonlinear and unpredictable aortic dilatation it is challenging to predict the AAA rupture using clinical diagnostics based on morphology No medical therapy is used clinically to treat AAA and there is an unmet need for clinically translatable molecular biomarkers of AAA disease activity for surveillance and patient-specific management The goal of this proposal is to develop a new approach for the diagnosis and targeted therapy of AAA
Detailed Description:
This project addresses the absence of a reliable diagnostic modality and medical therapy to prevent abdominal aortic aneurysm AAA growth and rupture in patients leading to high mortality in those over the age of 65 years old Due to the pathogenic role of the monocyte chemoattractant protein-1 C-C chemokine receptor type 2 MCP-1CCR2 axis in AAA we propose to study the ability of 64Cu-DOTA-ECL1i PETCT to predict the murine AAA rupture and serve as a companion diagnostic to assess CCR2 molecular therapy of murine AAA We will perform the first-in-patient evaluation of 64Cu-DOTA-ECL1i PETCT to image and detect AAA inflammation in a preoperative setting and acquire key biological information from AAA specimens collected at the time of open AAA repair in order to assess the potential of 64Cu-DOTA-ECL1i PET in the management of AAA patients
Preclinical and clinical research demonstrated that monocyte chemotactic protein-1 chemokine C-C motif receptor 2 MCP-1CCR2 plays an important role in the pathogenesis of AAAs This axis specifically promotes AAA formation and development by mediating the recruitment of circulating LY6Chigh monocytes and infiltration of macrophages which leads to the degradation of elastic and collagen In AAA mouse models the genetic depletion or specific inhibition of CCR2 significantly decreased the production of matrix metalloproteinases MMPs and formation of aneurysms suggesting the potential of CCR2 as a biomarker for AAA imaging and pre-screening for targeted intervention
We have developed a specific CCR2 binding radiotracer 64Cu-DOTA-ECL1i for targeted imaging of CCR2 positive pro-inflammatory monocytesmacrophages in multiple animal inflammatory models using positron emission tomography PET This investigational PET tracer is being used under Exploratory IND 137620 for research imaging studies in human subjects In patients with inflammatory diseases 64Cu-DOTA-ECL1i PET revealed specific detection of CCR2 cells in inflammatory tissues In a rat AAA model 64Cu-DOTA-ECL1i PET revealed specific localization within the aneurysm as well as sensitive detection of CCR2 inflammatory cells Human AAA specimens demonstrated specific binding of 64Cu-DOTA-ECL1i to CCR2 by autoradiography Thus we hypothesize that 64Cu-DOTA-ECL1i detect CCR2 cells mediated aneurysmal activity and can be utilized for AAA molecular imaging We propose to assess the potential of 64Cu-DOTA-ECL1i as a biomarker for AAA patients imaging
Preclinical and clinical research demonstrated that monocyte chemotactic protein-1 chemokine C-C motif receptor 2 MCP-1CCR2 plays an important role in the pathogenesis of AAAs This axis specifically promotes AAA formation and development by mediating the recruitment of circulating LY6Chigh monocytes and infiltration of macrophages which leads to the degradation of elastic and collagen In AAA mouse models the genetic depletion or specific inhibition of CCR2 significantly decreased the production of matrix metalloproteinases MMPs and formation of aneurysms suggesting the potential of CCR2 as a biomarker for AAA imaging and pre-screening for targeted intervention
We have developed a specific CCR2 binding radiotracer 64Cu-DOTA-ECL1i for targeted imaging of CCR2 positive pro-inflammatory monocytesmacrophages in multiple animal inflammatory models using positron emission tomography PET This investigational PET tracer is being used under Exploratory IND 137620 for research imaging studies in human subjects In patients with inflammatory diseases 64Cu-DOTA-ECL1i PET revealed specific detection of CCR2 cells in inflammatory tissues In a rat AAA model 64Cu-DOTA-ECL1i PET revealed specific localization within the aneurysm as well as sensitive detection of CCR2 inflammatory cells Human AAA specimens demonstrated specific binding of 64Cu-DOTA-ECL1i to CCR2 by autoradiography Thus we hypothesize that 64Cu-DOTA-ECL1i detect CCR2 cells mediated aneurysmal activity and can be utilized for AAA molecular imaging We propose to assess the potential of 64Cu-DOTA-ECL1i as a biomarker for AAA patients imaging
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None