CANF-Comb-II PET-MR in Atherosclerosis Multisite

Recruiting

• Conditions: Carotid Atherosclerosis; Carotid Artery Atheroma; Asymptomatic Carotid Artery Stenosis
• Interventions: Drug: 64Cu-25%-CANF-Comb

• Registration Number: NCT05838547
• Lead Sponsor: Washington University School of Medicine

Brief Summary

The goal of this observational study is to learn more about plaque biology in asymptomatic carotid artery stenosis (ACAS) patients through imaging. The main questions it aims to answer are:

* To determine the ability of 64Cu-CANF-Comb positron emission tomography (PET) to risk stratify ACAS patients for stroke event, to include transient ischemic attack or remote ipsilateral intervention.

* To further understand the role of Natriuretic Peptide Receptor C (NPRC) in the evolution of carotid atherosclerosis.

Participants will be asked to undergo a carotid PET-magnetic resonance imaging (MRI) examination to assess whether the carotid atherosclerosis uptake of 64Cu-CANF-Comb as measured by PET-MRI correlates with patient outcomes (stroke, transient ischemic attack, or remote ipsilateral intervention).

Detailed Description

This is an NIH-funded, Phase II, multicenter, open-label patient outcomes imaging study . Patients will undergo carotid PET/MRI after intravenous injection of 4-6 milliCuries (mCi) of the FDA Exploratory Investigational New Drug (eIND)-approved nanoparticle PET radiotracer (64Cu-C-type atrial natriuretic factor (CANF)-Comb). 80 subjects will be asymptomatic carotid artery stenosis (ACAS) patients with known carotid artery atherosclerosis by ultrasound/Doppler ≥ 60% diameter stenosis. These patients will be asked to undergo a carotid PET/MRI at a single time point 12-24 hours after intravenous injection of the 64Cu-CANF-Comb radiotracer.

Based on promising results from a proof of concept study, the investigators have devised an imaging protocol to determine the ability of 64Cu-25%-CANF-Comb PET to risk stratify ACAS patients treated with optimal medical therapy (OMT) alone with respect to patient outcomes. In this observational study, 80 patients with ACAS ≥ 60% will undergo 64Cu-25%-CANF-Comb PET/MRI. Patients will be maintained on either OMT alone or receive OMT and carotid endarterectomy (CEA) as determined by their treating vascular surgeon prior to imaging.

A total of 80 subjects, both men and women (≥18 years of age), will be recruited at Washington University (WU) and Cedars Sinai, with approximately 59 patients recruited at WU and approximately 21 patients recruited at Cedars Sinai. Patients will be asked to undergo carotid PET/MRI after intravenous injection of 64Cu-25%-CANF-Comb. These 80 subjects will be asymptomatic carotid artery stenosis (ACAS) patients with known carotid artery atherosclerosis by ultrasound/Doppler ≥ 60% diameter stenosis. These patients will be asked to undergo a carotid PET/MRI at a single time point 12-24 hours after intravenous injection of the 64Cu-25%-CANF-Comb radiotracer. Patients treated with OMT alone will undergo repeat PET/MRI at 12-18 months, or earlier if they develop symptoms. PET/MRI changes over the 12-18-month interval will be used to further understand the biology of carotid plaque evolution after treatment with OMT.

At the time of imaging, the investigators will record baseline medications to include any antiplatelet, statin, anti-hypertension, and diabetes medications (OMT), and basic risk factors and demographic information (e.g. diabetic, hypertensive, smoker, hypercholesterolemia), in addition to the patient's age and sex. Vital signs, a blood draw, and urinalysis will be obtained at baseline and at time of imaging (12-24 hrs after injection). A physical examination will be obtained at baseline and at the time of imaging. Telephone follow-up will occur within 48-72 hours (2-3 days) after discharge and then every 3 months (+/- 5 days) until the end of the study to assess for ipsilateral ischemic cerebrovascular event (TIA, stroke) or remote ipsilateral carotid intervention. This outcomes data will be used to answer the primary objective of this project.

Study Timeline

• Study Start: 2023-03-21
• Study First Submitted: 2023-04-09
• Study First Submitted QC: 2023-04-27
• Study First Posted: 2023-05-01
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-02
• Last Update Posted: 2024-05-06
• Primary Completion: 2027-05-31
• Study Completion: 2027-05-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

• Adults, 18 years of age or older
• Patients who have undergone carotid Doppler/ultrasound imaging which have demonstrated a ≥ 60% diameter carotid artery stenosis.
• The treating surgeon has planned either treatment with optimal medical therapy (OMT) alone, or OMT and carotid endarterectomy (CEA) surgical intervention.

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Exclusion Criteria

• Inability to receive and sign informed consent.
• Patients with an unstable clinical condition that in the opinion of the Sponsor-Investigator or designee precludes participation in the study.
• Inability to tolerate up to 60 minutes in a supine position with arms down at sides for PET-MR imaging.
• Prior history of CEA or carotid artery stent procedure.
• Past medical history of TIA or stroke within the last 6 months.
• Unwilling to comply with study procedures and/or unable to be available for the duration of the study outlined in the protocol.
• Contraindications to MR imaging (pacemaker, brain aneurysm clips, shrapnel, claustrophobia, etc.).
• Currently pregnant or lactating. All female subjects of childbearing potential must have a documented negative pregnancy test (serum or urine hCG) performed within 24 hours immediately prior to the administration of 64Cu-25%-CANF-Comb or documented post- menopausal defined as the cessation of menses for ≥ 12 months or documentation of having a bilateral oophorectomy and/or hysterectomy.

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Patients treated with OMT and carotid endarterectomy (CEA).	64Cu-25%-CANF-Comb	Asymptomatic carotid artery stenosis (ACAS) patients with known carotid artery atherosclerosis by ultrasound/Doppler ≥ 60% diameter stenosis who are clinically referred for OMT and CEA.
Patients treated with Optimal Medical Therapy (OMT) alone.	64Cu-25%-CANF-Comb	Asymptomatic carotid artery stenosis (ACAS) patients with known carotid artery atherosclerosis by ultrasound/Doppler ≥ 60% diameter stenosis who are clinically referred for OMT alone.

Primary Outcome Measures

Name	Time	Method
Number of patients reporting ipsilateral ischemic cerebrovascular (TIA, stroke) or remote ipsilateral carotid intervention	Through study completion, up to 4 years.	Patients will be contacted every 3 months after PET/MR imaging to assess for interval ipsilateral ischemic cerebrovascular event. In patients treated with OMT, it is anticipated that higher 64Cu-CANF-Comb PET signal (SUV) will correlate with increased ipsilateral ischemic cerebrovascular event (TIA, stroke) or remote ipsilateral carotid intervention (CEA surgery or stent placement); PET signal (SUV) will be assessed as a marker of risk for event in comparison to anatomic features of vulnerable plaque on MRI, with the goal of determining 64Cu-CANF-Comb PET signal above which suggests ACAS at higher risk.

Secondary Outcome Measures

Name	Time	Method
Changes in 64Cu-CANF-Comb PET signal - OMT	18 months.	Patients treated with OMT will be imaged at baseline and at 18 months to determine interval change in 64Cu-CANF-Comb PET signal (SUV) over time.
PET signal relative to presence of targeted receptor, NPR-C and histopathological features of plaque vulnerability - CEA surgery as Treatment	Immediately after surgery.	In patients who initially undergo CEA, PET signal (SUV) will be compared to ex vivo plaque vulnerability and NPRC cellular distribution to facilitate understanding of gene expression using immunohistochemistry (IHC) and cell lineage/origin through single cell RNA (scRNA)/cellular indexing of transcriptomes and epitopes (CITE)-seq.

Trial Locations

Locations (2)

Cedars Sinai Medical Center; 🇺🇸 Los Angeles, California, United States

Washington University in St. Louis; 🇺🇸 Saint Louis, Missouri, United States