A stiffened heart valve is being targeted by two bone drugs in a clinical trial with 150 patients. The drugs—denosumab and alendronate—normally treat osteoporosis by blocking calcium loss from bone, but the same calcium metabolism may be driving the progressive narrowing of the aortic valve. Currently, the only treatment for severe aortic stenosis is surgical valve replacement. This trial tests whether either drug can slow or stop the valve from hardening, using PET scans that track radioactive fluoride binding to fresh calcium deposits. If the drugs reduce that signal, it would suggest a medical—rather than surgical—way to halt the disease. The trial is a foundation for a larger, definitive study with clinical outcomes such as hospitalisation or death. The researcher will also train in New York on combined PET/MRI and nanoparticle imaging, skills that could later be applied to other cardiovascular conditions. This is an early-stage clinical trial; it will not change patient care immediately, but it could open a new class of treatments for a common, life-threatening condition.
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In my proposed intermediate clinical research fellowship, I intend to expand my expertise in multimodal cardiovascular imaging in two distinct ways. First, I will gain experience in leading and delivering a randomised clinical trial with imaging end-points. Specifically I will perform a double-blind randomised controlled trial of two therapies targeted at calcium metabolism (denosumab and alendronate) in patients with aortic stenosis. Response to therapy will be assessed in 150 patients using aortic valve 18F- fluoride uptake, aortic valve calcium scoring, and the peak aortic jet velocity. This will determine whether such interventions have the potential to inhibit disease progression and provide the foundation for a subsequent definitive trial using clinical end-points. Moreover it will provide me with the training and expertise with which to conduct similar imaging trials of novel therapies in my future career. Second, I will undertake an imaging fellowship at Mount Sinai Hospital, New York to gain unique experience in combined positron emission tomography / magnetic resonance imaging (PET/MRI) in addition to state-of-the-art multi-modality molecular imaging using nanoparticles. I believe this fellowship will provide me with the necessary clinical trial and imaging skills to establish my own cardiovascular research programme using a wide range of imaging techniques, molecular tracers and contrast agents.
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