Clinical trial NCT05838547: CANF-Comb-II PET-MR in Atherosclerosis Multisite
Official title: PET-MR Imaging of Natriuretic Peptide Receptor C (NPR-C) in Carotid Atherosclerosis With Cu[64]-25%-CANF-Comb-II
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Carotid Atherosclerosis
Asymptomatic Carotid Artery Stenosis
Carotid Artery Atheroma
Keywords: Stroke
TIA
Vascular Disease
Cardiovascular Disease
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: Cedars-Sinai Medical Center
name: University of California, Santa Barbara
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2023-05-01
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Individuals ≥18 years of age with asymptomatic carotid artery stenosis.

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.

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.

Primary outcomes:
measure: Number of patients reporting ipsilateral ischemic cerebrovascular event (TIA, stroke) or remote ipsilateral carotid intervention
timeFrame: Through study completion, up to 4 years.
Secondary outcomes:
measure: Changes in 64Cu-CANF-Comb PET signal - OMT
timeFrame: 12-18 months (preferred); through study completion, up to 4 years.
measure: PET signal relative to presence of targeted receptor, NPR-C and histopathological features of plaque vulnerability - CEA surgery as Treatment
timeFrame: Immediately after surgery.
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Saint Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Pamela Woodard, MD
role: PRINCIPAL_INVESTIGATOR
References: