Clinical Core Abstract The human core developed through the first 4 years has become an established center for translational research in pulmonary hypertension (PH), encompassing a large biorepository and clinical trials coordinating center. The goal of the human core during this renewal is to support all Research Projects by 1) providing the infrastructure and expertise necessary to conduct clinical trials of new therapies of dietary supplements for Group I and Group II PH, and 2) collecting hemodynamic, clinical, biomarker, and microbiome data on PH patients for robust phenotyping. Specific expansions of the human core for this renewal include enrollment of Groups I-V PH patients into the human subphenotyping core registry to provide mechanistic insight into endo- phenotypes of PH including the role of the microbiome in PH, collection of pulmonary artery endothelial cells during clinical right heart catheterization, as well as harvest of isolated endothelial, smooth muscle and lung fibroblasts from human lungs of PH patients removed at time of transplantation. The core will draw on the extensive clinical and research infrastructure harnessed during the first phase of the TPPG including 14 clinics, over 1,000 clinical right heart catheterization each year, 34 ongoing NIH- or industry-funded research projects, over 2,500 biospecimens banked, a vascular clinical translational research center specializing in assessment of endothelial function for 9 NIH- or industry-funded research projects, and over 1,200 patients enrolled in clinical trials over the past five years. The human core is critical to all Projects to fulfill the translational directive of the TPPG, in which each Project will conduct a clinical or translational trial. This unmatched resource will accelerate the pace of discovery in the Projects by rapidly identifying appropriate patients for clinical trials and by providing a wealth of biospecimens with corresponding clinical data for mechanistic investigations.
Clinical Core Narrative Pulmonary hypertension (PH), is a heterogenous disease with poor outcomes and, in particular, limited therapies when it occurs in the context of other heart or lung disorders. In this tPPG, we have found that certain ?sub-phenotypes,? such as the metabolic syndrome, may have a profound impact on mechanisms of disease development, outcomes, and response to therapy, which this renewal will study in detail. The clinical core of this tPPG will continue to provide, as well as expand upon, the infrastructure and expertise necessary to conduct the translational clinical trials of each project along with housing a human subphenotyping core registry. Clinical trial support will leverage our center?s large pulmonary hypertension center that encompasses 14 clinics, over 1,000 clinical right heart catheterizations each year, and over 1,200 patients enrolled in clinical trials over the past five years. The human subphenotyping core registry will be expanded to enrollment of all PH etiologies, biospecimen collection building upon the >16,000 blood samples to also include oral/stool for microbiome analysis and pulmonary artery endothelial cell banking for mechanistic studies.
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