Interventional - Drug
The TaRGET trial is a multi-centre, prospective, randomized, double-blind, placebo-controlled trial designed to evaluate the potential therapeutic efficacy of tideglusib, a glycogen synthase kinase-3 beta (GSK3β) inhibitor, in genotype positive arrhythmogenic cardiomyopathy (ACM).
ACM is a heritable form of structural heart disease characterized by myocardial fibrosis that confers vulnerability to malignant ventricular arrhythmias and sudden cardiac death (SCD). A subgroup of cases preferentially involves the right ventricle and is termed arrhythmogenic right ventricular cardiomyopathy (ARVC). Insight into its pathophysiology remains modest. A lack of understanding of its operative biological pathways has rendered development of tailored treatments challenging, leading to approaches to medical therapy being largely adopted from those utilized for more common forms of cardiomyopathy.
In 2014, a high-throughput screen of a library of bioactive compounds against a zebrafish model of ACM identified a small molecule classified as a GSK3 inhibitor that successfully prevented and rescued the phenotype, findings that have subsequently been reproduced in a series of ACM murine models. GSK3 is an enzyme that modulates the activity of a broad spectrum of intracellular signaling pathways, including the canonical Wnt/β-catenin pathway, whose suppression has been suggested to exert an important role in ACM pathogenesis.
Tideglusib is an oral GSK3β inhibitor with an established safety profile in humans. Driven by promising findings observed for tideglusib in ACM mouse models, we now seek to evaluate its potential efficacy in a randomized clinical trial involving genotype positive ACM patients.
Change in mean PVC count per 24 hours on 7-day Holter between baseline and 6 months.
Interventional - Drug
Double blinded, placebo-controlled
Population Health Research Institute
Stuart Connolly is a Professor of Medicine at McMaster University and a cardiac electrophysiologist at Hamilton Health Sciences. He became a faculty member at McMaster University in 1983 and was awarded a full professorship in 1994. He was also appointed as the inaugural holder of the Salim Yusuf Chair in Cardiology at McMaster University.
He has published more than 270 scientific articles in the field, and is currently a member of the editorial boards for a number of prominent cardiology journals, including Heart, the American Heart Journal and the Journal of Pacing and Electrophysiology. His main research interests are focused on the evaluation of treatments for heart rhythm disorders. His academic career has been largely devoted to the design and execution of controlled clinical trials in this area.
He holds a Masters degree from Fordham University, New York, and an MD from McGill University in Montreal. He received his specialist training in cardiology at the University of Toronto and at Stanford University.
Jason Roberts is a clinical cardiac electrophysiologist at Hamilton Health Sciences and an Associate Professor of Medicine at McMaster University. As a clinician researcher, Jason’s interests focus on the genetics of cardiac arrhythmias, and evaluating the clinical utility of new drugs and gene-based therapies as treatments for both rare and common forms of cardiac arrhythmias. Previously, he worked at the University of Western Ontario as part of the London Heart Rhythm Program, where his research focused on refining insights into the clinical and genetic features of inherited arrhythmia syndromes.
He completed his training in cardiac electrophysiology at the University of California, San Francisco (UCSF) and his cardiology fellowship at the University of Ottawa Heart Institute, during which he worked with Spartan Biosciences to develop the first point-of-care genetic test in clinical medicine (trial results published in The Lancet). He holds a Master’s degree in clinical epidemiology and biostatistics from UCSF.
Sumathy Rangarajan has been Program Director, Global Health, since 2016, preceded by many years’ service at PHRI in other roles. She oversees the PURE study team, as well as the INVICTUS rheumatic AF treatment trial, the CANPWR pediatric weight management registry, and others.
She holds both a Bachelor of Science Degree and a Master of Science degree from Pune University in India.
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