CANF-Comb-II PET-MR in Atherosclerosis Multisite

NCT ID: NCT05838547

Last Updated: 2025-04-02

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 80 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-03-21
• Study Completion Date: 2027-05-31

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). A total of 80 subjects will be recruited to this study. These subjects will be asymptomatic carotid artery stenosis (ACAS) patients with known carotid artery atherosclerosis by ultrasound/Doppler or other carotid imaging ≥ 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 or other carotid imaging ≥ 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. While 12-18 months is the preferred window for repeat PET/MRI, if imaging during this time frame is not achievable, the patient may return anytime throughout the remainder of the study. PET/MRI changes over time 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.

Conditions

Carotid Atherosclerosis; Asymptomatic Carotid Artery Stenosis; Carotid Artery Atheroma

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Patients treated with Optimal Medical Therapy (OMT) alone.

Asymptomatic carotid artery stenosis (ACAS) patients with known carotid artery atherosclerosis by ultrasound/Doppler or other carotid imaging ≥ 60% diameter stenosis who are clinically referred for OMT alone.

64Cu-25%-CANF-Comb

Intervention Type: DRUG

Patients treated with OMT alone that are not treated with CEA will receive an intravenous injection of 4-6 mCi of 64Cu-25%-CANF-Comb radiotracer for PET/MR imaging at the initial imaging visit and at 12-18 months, or earlier if they develop symptoms. While 12-18 months is the preferred window for repeat imaging, if imaging during this time frame is not achievable, the patient may return anytime throughout the remainder of the study.

Patients treated with OMT and carotid endarterectomy (CEA).

Asymptomatic carotid artery stenosis (ACAS) patients with known carotid artery atherosclerosis by ultrasound/Doppler or other carotid imaging ≥ 60% diameter stenosis who are clinically referred for OMT and CEA.

64Cu-25%-CANF-Comb

Intervention Type: DRUG

Patients treated with OMT and CEA will receive an intravenous injection of 4-6 mCi of 64Cu-25%-CANF-Comb radiotracer for PET/MR imaging at the initial imaging visit.

Interventions

64Cu-25%-CANF-Comb

Patients treated with OMT alone that are not treated with CEA will receive an intravenous injection of 4-6 mCi of 64Cu-25%-CANF-Comb radiotracer for PET/MR imaging at the initial imaging visit and at 12-18 months, or earlier if they develop symptoms. While 12-18 months is the preferred window for repeat imaging, if imaging during this time frame is not achievable, the patient may return anytime throughout the remainder of the study.

Intervention Type: DRUG

64Cu-25%-CANF-Comb

Patients treated with OMT and CEA will receive an intravenous injection of 4-6 mCi of 64Cu-25%-CANF-Comb radiotracer for PET/MR imaging at the initial imaging visit.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Adults, 18 years of age or older
• Asymptomatic carotid artery stenosis patients who have undergone carotid Doppler/ultrasound imaging or other carotid 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.

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 on the ipsilateral side.
• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cedars-Sinai Medical Center

OTHER

Sponsor Role: collaborator

University of California, Santa Barbara

OTHER

Sponsor Role: collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Pamela Woodard, MD

HM Wilson Professor of Radiology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Pamela Woodard, MD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Cedars Sinai Medical Center

Los Angeles, California, United States

Site Status: RECRUITING

Washington University in St. Louis

St Louis, Missouri, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Molly Mohrman

Role: CONTACT

mohrmanm@wustl.edu

314-747-4633

Pamela Woodard, MD

Role: CONTACT

woodardp@wustl.edu

314-362-7100

Facility Contacts

Yibin Xie, Ph.D

Role: primary

Yibin.Xie@cshs.org

Pamela K Woodard, MD

Role: primary

woodardp@wustl.edu

Other Identifiers

123,617

Identifier Type: OTHER

Identifier Source: secondary_id

R01HL159803

Identifier Type: NIH

Identifier Source: secondary_id

View Link

202210116

Identifier Type: -

Identifier Source: org_study_id