Clinical Research Directory

CANF-Comb-II PET-MR in Atherosclerosis Multisite

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).

3D Contrast Enhanced Microvascular Ultrasound of Carotid Atherosclerosis for the Detection of Carotid Plaque Neo-Revascularisation.

Atherosclerotic plaques, the build-up of fatty materials within our arteries, can develop over a long period of time without causing any symptoms. These plaques may continue to grow and rupture causing narrowing and blockages of the blood vessels. This can lead to serious cardiovascular disease such as a heart attack or stroke causing over 160,000 deaths each year. Lots of research has been done on why particular groups of people may develop atherosclerosis and controlling risk factors such as diabetes and high blood pressure go a long way to reduce people's risks. However, despite the treatments we have available and controlling these risk factors, some people unfortunately still go on to develop a potentially serious disease. Further research has shown us that certain plaques in the blood vessels may be more vulnerable to rupturing compared to others. So far we know that plaques with thin caps, soft centres or those that are able to grow their own tiny blood vessels are more likely to rupture. We have now started to develop new imaging methods to try and help us detect these vulnerabilities. The hope is by being able to detect more vulnerable plaques we may be able to treat these earlier and therefore more effectively. There are different scans available to try and visualise the tiny vessels within these plaques in the neck arteries. These include, MRI (a Magnetic Resonance Imaging scan, taking pictures using a small tunnel), CT (Computed Tomography, uses a ring-shaped machine to take pictures), and ultrasound. Ultrasound has the benefit of being free of ionising radiation and iodinated contrast, therefore posing less risk to patients. However, current ultrasound uses 2D ultrasound. Although this has shown promising results, our blood vessels and any plaques are 3D structures so we don't get to see the whole plaque using 2D imaging and therefore may miss important information. The available 3D probes in use at the moment are not able to visualise the tiny vessels accurately enough. This study uses a different 3D ultrasound probe and ultrasound machine that is able to produce many more images than our usual probes. By taking images with this probe and using offline computer programmes to track the contrast through structures we hope that this system will be able to give us a visualisation of the whole plaque enabling us to detect any new blood vessels more accurately.

Prediction of Cerebral Hyperperfusion Syndrome After Carotid Revascularization Using Deep Learning

Cerebral hyperperfusion syndrome (CHS) was initially described as a clinical complication following carotid endarterectomy (CEA), but it may occur after both CEA and carotid artery stenting. It is characterised by throbbing ipsilateral frontotemporal or periorbital headache, and sometimes diffuse headache, eye and facial pain, vomiting, confusion, macular oedema, visual disturbances, focal motor seizures with frequent secondary generalisation, focal neurological deficits, and intracerebral or subarachnoid haemorrhage. Knowledge of CHS among physicians remains limited. Most studies report an incidence of 1-3% after carotid endarterectomy. CHS is most common in patients with increases of more than 100% in cerebral perfusion compared with baseline after carotid revascularization, and is rare in patients with perfusion increases of less than 100% compared with baseline. The pathophysiological mechanism of CHS is only partially understood. The chronic low-flow state induced by severe carotid disease results in compensatory dilation of cerebral vessels distal to the stenosis, as part of the normal autoregulatory response to maintain adequate cerebral blood flow (CBF). In this chronically dilated state, the vessels lose their ability to autoregulate vascular resistance in response to changes in blood pressure. Dysautoregulation has been shown to be proportional to the duration and severity of chronic hypoperfusion. After revascularization and reperfusion, impaired cerebral autoregulation may contribute to a cascade of intracranial microcirculatory changes, with an inability to respond adequately to the augmentation of CBF following carotid recanalization. Although most patients present with mild symptoms and signs, progression to severe and life-threatening complications can occur if CHS is not recognised and treated promptly. Because CHS is diagnosed on the basis of several non-specific signs and symptoms, patients may be misdiagnosed as having one of the better-known causes of perioperative complications, such as thromboembolism.

Microflow3D - Non-invasive Mapping of Coronary Arteries and the Cerebral Vascular Network Using 3D Ultrasound Localization Microscopy in Patients With Atherosclerosis Prior to Carotid Endarterectomy Surgery

There is a need to simplify the assessment of coronary and cerebral vascular networks in patients selected for carotid endarterectomy in order to prevent potential complications during and after surgery. A non-invasive, non-ionizing 3 dimension mapping of these networks would provide a remarkable benefit for patients.

Impact of Treating Severe Periodontitis on Inflammatory Activity of Atheromatous Plaques in Patients With Acute Myocardial Infarction (AMI)

Multicenter randomized clinical trial with two arms in patients hospitalized for an AMI nested in the Frenchie registry. Periodontal therapy is performed by periodontists in the intervention group versus treatment by dental surgeons as part of their usual practice in the control group. For the intervention group, periodontal management will be carried out for a maximum of 6 months after randomisation, prolonged by a follow-up of 6 months including a maintenance visit at M9. All patients will have an FDG-PET at M0 and M12 for evaluation of inflammation on carotid atherosclerotic plaques.

PET Detection of CCR2 in Human Atherosclerosis

: Use of novel radio-pharmaceutical 64CUDOTA-ECL1i to evaluate arterial atherosclrosis

The Effect of Low-dose Interleukin-2 on the Immune Landscape of Human Atherosclerotic Plaques at Single Cell Resolution.

The goal of this clinical trail is to compare the differences in carotid plaque Treg cells' gene signature for activation, proliferation, and suppressive function using scRNA-seq in patients treated with IL-2 compared to control.

Risk Assessment of Carotid Plaques Using 3D Contrast-Enhanced Ultrasound

This is an open-label, non-randomized study conducted at Thomas Jefferson University comparing pressure-gradient estimates (obtained between a carotid plaque and the carotid artery) to imaging and histology markers of plaque vulnerability. There is an inverse relationship between the subharmonic signal magnitude from contrast-enhanced ultrasound microbubbles and ambient pressure. This pressure estimation technique (referred as SHAPE) will be used to estimate the pressure gradient across the carotid plaque cap noninvasively in vivo.

Shear Wave Elastography for Carotid Atherosclerotic Plaques

The goal of this prospective diagnostic accuracy cohort study is to compare the accuracy of carotid atherosclerotic plaques stiffness assessed by shear wave elastography (SWE) with greyscale median values (GSM), magnetic resonance imaging (MRI) and histopathological findings in patients with carotid atherosclerotic plaques causing stenosis above 50%, symptomatic or not. The main question it aims to answer is: is the plaque stiffness correlatable with GSM values, MRI findings or histopathological findings? Participants will be subjected to a vascular ultrasound study in which the SWE and GSM will be assessed. The second imaging modality for stenosis confirmation will be MRI and patients with confirmed symptomatic stenosis above 50% or assymptomatic stenosis above 70% will be considered for surgery intervention (endarterectomy or angioplasty). Patients that undergo endarterectomy will have the carotid plaques subjected to a histopathological study. The study will not arbitrate about the treatment decision.

Coated or Chewable Aspirin and a Hybrid Strategy to Mitigate Adverse Effects of Air Pollution in Stable Atherosclerotic Disease

Although both enteric-coated and plain formulations of aspirin are being used commonly, there are no high-quality comparisons between these formulations with respect to clinical efficacy outcomes in patients with atherosclerotic cardiovascular diseases (ASCVD). Air pollution is also a major contributor to the excess risk of cardiovascular events in many regions of the world. However, little is known about the effect of individual-level mitigation strategies against air pollution in reducing cardiovascular outcomes. The purpose of the first randomization is to compare the efficacy and safety of enteric-coated versus plain low-dose (81 mg) aspirin formulations in a double-blind fashion. The second randomization compares a multifaceted intervention including one-page educational flashcard, cell phone text messages alerting participants on polluted days, recommending them to stay indoors or wear KN-95 facemasks provided by the study team in case of necessary outdoor activity, and recommendation to consume citrus fruits on polluted days versus usual care. Both randomization are powered for clinical outcomes and the results will inform practice.

Evaluating the Impact of 'Tertinat' on Patients with Atherosclerosis-Related Cardiovascular Diseases

The aim of this clinical trial is to evaluate whether the biologically active food supplement, Tertinat, can influence atherosclerosis progression in adults and improve the treatment outcomes of cardiovascular diseases. The study will assess the frequency of fatal and clinically significant cardiovascular events, monitored every 12 months following participants\' inclusion in the trial. Additionally, the trial will evaluate Tertinat's ability to prevent pro-atherogenic modification of lipoproteins and its impact on inflammatory activity. To this end, levels of desialylated low-density lipoproteins (LDL) and inflammatory markers in the blood will be monitored. Tertinat administration will occur alongside the standard therapy prescribed to patients based on their existing medical conditions. Researchers will compare the effects of the Tertinat supplement to a placebo (an identical-looking substance that does not contain the active supplement) to determine if Tertinat is effective in reducing cardiovascular events . Participants will: Take either Tertinat or a placebo daily for a duration of 24 months. Visit the clinic once a year for check-ups and testing.

The Role of Maintaining External Carotid Artery Flow in Graft Interposition After Carotid Endarterectomy

Analyzing results of carotid graft interposition with and without flow preservation through external carotid artery after endarterectomy.

Carotid Artery Stenting During Endovascular Treatment of Acute Stroke

Rationale: Approximately 20% of the patients with acute ischemic stroke due to an intracranial large vessel occlusion (LVO) has a high-grade stenosis in the ipsilateral cervical carotid artery. It is uncertain whether immediate carotid artery stenting (CAS) of a cervical carotid artery stenosis during endovascular thrombectomy (EVT) is beneficial. Immediate CAS could improve cerebral perfusion and prevent recurrent ischemic stroke but could also increase the chance of intracranial hemorrhagic complications due to hyperperfusion syndrome or to the required antiplatelet treatment to prevent stent occlusion. Moreover, some patients end up with a severe disabling stroke after EVT. In these patients carotid revascularization by carotid endarterectomy (CEA) or CAS would usually not be performed but these patients would be treated by medical management only. Objective: to assess the safety and efficacy of immediate cervical CAS during EVT in patients with acute ischemic stroke due to LVO with a high-grade stenosis \>50% or occlusion of the ipsilateral cervical carotid artery. Study design: prospective randomized open label controlled trial comparing immediate CAS during EVT versus EVT with deferred treatment of the cervical carotid artery lesion (deferred CAS/CEA or medical management alone). Outcome assessment will be blinded for treatment allocation.

Carotid Atherosclerosis in Predicting Coronary Artery Disease

Carotid plaque burden and composition features, particularly lipid necrotic core, are significantly associated with severity of CAD stenosis. This study aims to explore the relationship between various phenotypic patterns of carotid atherosclerosis with the prevalence, phenotype, and severity of coronary atherosclerosis. The patients with chest tightness or chest pain will receive carotid artery ultrasonography before coronary angiography so as to explore the relationship between them.

The Intersectional Viborg Screening Program: Cost-(Effectiveness) of Screening for Diabetes and Cardiovascular Diseases

This is an intersectional and interdisciplinary screening program in Viborg Municipality, including 67 years old citizens. This observational study will estimate the cost-effectiveness of a combined screening program for the following conditions: Abdominal aortic aneurysm, peripheral arterial disease, carotid plaque, hypertension, arrhythmia, and type-2-diabetes. Furthermore, the incidence of the outlined conditions will be described and so will the result of the intervention initiated (secondary medical prophylaxis, smoking cessation, introduction to nutritionally deficient diet etc.)

Atherosclerosis in Juvenile Mixed Connective Tissue Disease (ACTID)

This Study investigates presence of preclinical atherosclerosis in patients with Juvenile Mixed Connective Tissue Disease in Norway.