Clinical Research Directory

Long-Axial Field of View (LAFOV) [18F]FDG PET/CT Imaging in Large Vessel Vasculitis (LVV): Protocol Optimisation Study.

Large vessel vasculitis (LVV) is an autoimmune inflammatory disorder affecting the major arteries of the body. The diagnosis and monitoring this condition can be challenging, as patients often present with symptoms that are unclear, and the diagnostic criteria currently used are varied. Accurate diagnosis is essential because it helps to tailor the treatment to each patient. Some treatments, such as steroids and immunosuppressive medications, can have significant side effects, so they need to be used carefully and only when truly needed. An \[18F\]FDG Positron Emission Tomography/Computed Tomography (PET/CT) involves the injection of a small amount of radiolabelled sugar, which assesses glucose metabolism within the body. \[18F\]FDG PET/CT is already used by the NHS to detect inflammation within the vessel walls and diagnose LVV. Current diagnostic criteria for LVV largely rely on visual assessment by a radiologist. This approach therefore has limitations and may not fully capture changes in the levels of inflammation over time. A new generation of scanners, known as Long Axial Field-of-View (LAFOV)-PET/CT or Total Body PET, are currently transforming what is possible in the field of medical imaging. These LAFOV-PET/CT scanners have new digital detectors that are more sensitive, produce sharper images, and can scan the entire body rapidly. This offers several potential advantages for patients with LVV, including the clearer detection of vessel wall inflammation, the ability to administer lower doses of the radiolabelled sugar (\[18F\]FDG), and the ability to take repeated pictures over time to measure subtle changes in blood flow and inflammation. Patients receiving a routine NHS \[18F\]FDG PET/CT scan for LVV are typically scanned 60 minutes after injection of the radiotracer using a standard PET/CT. Another benefit of LAFOV-PET/CT scanners is their ability to assess the amount of the radiolabelled sugar taken up by the whole body almost as soon as it is injected which could give important additional information. As part of the LAVA-FLOW study we are planning to combine LAFOV-PET/CT with a CT Angiogram (CTA) in patients with LVV. A CTA is a scan that shows doctors what your blood vessels look like. It involves the injection of a dye into a vein that makes your blood vessels visible, highlighting vessel wall inflammation and vessel wall narrowing. This combination of LAFOV-PET/CT and CTA therefore has the potential to give a much more detailed picture of LVV than is achievable using current methods. The LAVA-FLOW study therefore aims to develop a standardised protocol to be used in different hospital centres across the UK for the imaging of LVV using LAFOV-PET/CT. We also hope that the results of this particular study could lead to further larger studies with the potential to update the diagnostic criteria and improve the monitoring of this condition.

Comparison of NeuroEXPLORER PET/CT Versus Standard-of-care PET/CT of the Head and Neck Region.

The goal of this clinical study is to compare the current standard-of-care PET/CT scanner with the new NeuroEXPLORER PET/CT, with the aim of demonstrating the added diagnostic value of the new scanner. As this is the first device of its kind in Europe, the study will also evaluate the safety and general feasibility of the NeuroEXPLORER system for head and neck PET studies. Due to to its high resolution, the NeuroEXPLORER enables an accurate investigation of areas up to 20 times smaller than what can be visualized with standard clinical PET scanners, providing images with a very high level of detail. This scanner is specifically designed for imaging the brain, spinal cord, and neck region, to support the diagnosis and monitoring of neurological, psychiatric, and other disorders in the head and neck. The main questions this study aims to answer are: * Does the NeuroEXPLORER provide more detailed information with better diagnostic quality compared to standard clinical PET/CT scans for head and neck disorders? * Is the NeuroEXPLORER system safe and effective in performing head and neck studies? Participants will: * receive clear information about the study, including its organization, possible risks, and potential benefits. Based on this, they will be able to give their informed consent by signing an informed consent form before the study begins. * visit the clinic (UZ Leuven) once for two consecutive PET/CT scans: first the prescribed clinical scan, followed by a shorter scan with the NeuroEXPLORER. * before the start of the regular PET/CT scan, have a small catheter placed in a blood vessel in the forearm. Through this, a tracer will be administered. A tracer is a small amount of slightly radioactive material that helps to produce images of processes inside the body. Depending on the tracer used, the PET/CT scan may start immediately or after a short waiting period. * lie on their back on the scanner bed for 10 to 30 minutes during the clinical scan. * after the clinical scan, undergo a 15-20 minute scan on the NeuroEXPLORER. * leave the hospital after completing both scans. * afterwards, be asked whether they experienced any discomfort during the study. In addition, they will receive a one-time follow-up phone call within a week after the scan to check if they experienced any discomfort in the days following the study.

Risk of Diabetes Mellitus in Patients With Giant Cell Arthritis and Polymyalgia Rheumatica.

The goal of this observational study is to expand the knowledge about development and aggreviation of diabetes mellitus in patients with giant cell arthritis and polymyalgia rheumatica. The main questions it aims to answer are: * To identify the risk of comorbidities, especially diabetes, in patients with giant cell arthritis and polymyalgia rheumatica, treated with glucocorticoids in combination with or without interleukin-6 inhibitor. * To identify clinical outcomes and biomarkers as potential predictors for development or aggregation of already existing diabetes mellitus in patients with giant cell arthritis or polymyalgia rheumatica using machine learning prediction. Participants will be followed at their respective rheumatology clinic, and will be asked to deliver blood samples at predefined visits.

Phase II Interventional Study Evaluating Efficacy and Safety of Secukinumab in Active Severe Takayasu Patients

Takayasu's arteritis (TAK) is a large vessel vasculitis preferentially affecting the aorta and its main branches, leading to wall vessels thickening, fibrosis, stenosis, and occlusion. Patients with TAK have a high morbidity rate, 50% will relapse and experience a vascular complication within 10 years from diagnosis. TAK inflammation is mediated by T cells and macrophages. Pro-inflammatory Th1 and Th17 cells are dominant infiltrates in the vascular walls, producing IFN-γ and IL-17 to drive the systemic and vascular manifestations of TAK. Currently, TAK patients are principally treated with non-specific steroids, which are associated with potential side effects, especially when used for a long-time course. Steroid treatment preferentially target innate cytokines, such as IL-1β, IL-12, and IL-6 but have little effect on tissue-residing T cells. Novel approach needs to eliminate all T-cell effectors. The use of classical immunosuppressive drugs (IS) (methotrexate, Leflunomide) and biotherapies are prescribed earlier in the management of the disease in order to improve remission, spare corticosteroids and reduce relapses. Data from observational series report remission in 37-76% of cases with anti TNF alpha and 68% with Tocilizumab. However, a placebo-controlled trial failed to show superiority of tocilizumab in TAK. To date, no immunomodulatory treatment has been approved for the management of TAK and corticosteroids sparing remains a major challenge in this disease. Our team has demonstrated the key role of Th1 and Th17 responses in the pathophysiology of TAK. We found that Th17 and Th1 pathways contribute to the systemic and vascular manifestations of TAK and glucocorticoid treatment suppresses Th1 cytokines but spares Th17 cytokines in patients with TAK. Other teams further confirmed the significant increase in Th17 axis in TAK, and its correlation with disease activity, clinical relapse and arterial fibrosis. Secukinumab is a fully human monoclonal antibody that selectively inhibits IL-17A. Secukinumab received approval for adult treatment of moderate to severe plaque psoriasis, active psoriatic arthritis, active non-radiographic axial spondyloarthritis, and active ankylosing spondylitis in numerous countries, including the EU and the USA Recently, a phase II clinical trial assessing the efficacy and safety of secukinumab vs placebo in combination with glucocorticoid taper regimen in giant cell arteritis showed that patients with active giant cell arteritis had a higher sustained remission rate in the secukinumab group than in the placebo group at week 28, and is now being studied in a phase 3 study (NCT04930094).Secukinumab was well tolerated with no new safety concerns. In TAK, recent observational data suggested that secukinumab might be an effective alternative to TNFi in severe TAK patients. Inhibition of IL-17A could represent a potential new therapeutic option for the treatment of severe TAK disease, hence the need for a prospective study to evaluate secukinumab in the management of active severe TAK.

Dapagliflozin and Endothelin Receptor Antagonism in Large Vessel Vasculitis (DERAIL-LVV)

Large vessel vasculitis (LVV) is a disease that causes damage to blood vessels. This damage to blood vessels can increase the risk of patients with LVV developing cardiovascular disease, including heart attacks and strokes. A chemical produced in the body called endothelin may contribute to this increase in cardiovascular disease risk by causing the vessels to stiffen and blood pressure to increase. It has previously been shown that by blocking the effects of endothelin, vessel stiffness and blood pressure improve. Bosentan is a tablet that blocks the effects of endothelin. Dapagliflozin is a sodium-glucose co-transporter 2 inhibitor that has been shown to improve blood vessel function and stiffness in patients with diabetes. The investigators plan to assess blood vessel function in those with LVV and participants without LVV. Participants with LVV will be given Bosentan and Dapagliflozin for 6 weeks, followed by Dapagliflozin for 4 weeks, to evaluate their impact on blood vessel function.

Prediction of Risk of Vascular Structural Damage in Patients With Large Vessel Vasculitis (LVV) Based on PET/MRA Image Evaluation System

Large vessel vasculitis (LVV) causes vascular inflammation, leading to serious complications such as aneurysm formation and stroke. It is difficult to identify the inflammation of the vessel wall by the current imaging methods, thus affecting the timing of treatment and selection of treatment options. Improved examination methods to determine disease activity are highly needed to guide treatment.