Targeted Therapy With Glycogen Synthase Kinase-3 Inhibition for Arrhythmogenic Cardiomyopathy (TaRGET)
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT06174220 |
Recruitment Status :
Not yet recruiting
First Posted : December 18, 2023
Last Update Posted : February 22, 2024
|
Tracking Information | |||||||
---|---|---|---|---|---|---|---|
First Submitted Date ICMJE | December 1, 2023 | ||||||
First Posted Date ICMJE | December 18, 2023 | ||||||
Last Update Posted Date | February 22, 2024 | ||||||
Estimated Study Start Date ICMJE | April 1, 2024 | ||||||
Estimated Primary Completion Date | February 1, 2026 (Final data collection date for primary outcome measure) | ||||||
Current Primary Outcome Measures ICMJE |
PVC burden [ Time Frame: Baseline and 6 months ] Change in mean PVC count per 24 hours on 7-day Holter
|
||||||
Original Primary Outcome Measures ICMJE | Same as current | ||||||
Change History | |||||||
Current Secondary Outcome Measures ICMJE |
|
||||||
Original Secondary Outcome Measures ICMJE | Same as current | ||||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||
Descriptive Information | |||||||
Brief Title ICMJE | Targeted Therapy With Glycogen Synthase Kinase-3 Inhibition for Arrhythmogenic Cardiomyopathy | ||||||
Official Title ICMJE | Targeted Therapy With Glycogen Synthase Kinase-3 Inhibition for Arrhythmogenic Cardiomyopathy | ||||||
Brief Summary | The TaRGET study 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 β inhibitor, in genotype positive arrhythmogenic cardiomyopathy. | ||||||
Detailed Description | Arrhythmogenic cardiomyopathy (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). Although an increasingly diverse set of genes have been implicated in ACM, its most prominent genetic culprits are constituents of the desmosome, a specialized cellular structure within the intercalated disc that mediates intercellular adhesion. An additional ACM genetic subtype develops secondary to the TMEM43-p.S358L variant and is associated with an aggressive clinical phenotype, particularly among males. Despite dramatic progress in unravelling the genetic underpinnings of ACM, 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. An implantable cardioverter defibrillator (ICD) is recommended for prevention of SCD for all ACM patients considered high risk for malignant ventricular arrhythmias, however does not address its underlying pathophysiology. Subsequent prevention of painful ICD shocks for ventricular tachycardia often requires interventions that may carry modest efficacy and significant risks for adverse events, including anti-arrhythmic drugs and invasive combined endo- and epicardial catheter ablation procedures. 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 glycogen synthase kinase-3 (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. |
||||||
Study Type ICMJE | Interventional | ||||||
Study Phase ICMJE | Phase 2 | ||||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Intervention Model Description: Patients will be randomized in a 1:1 ratio using an automated central, web-based system within 30 days of completing their baseline Holter. Randomization will be stratified by TMEM43-p.S358L variant status. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)Primary Purpose: Treatment |
||||||
Condition ICMJE |
|
||||||
Intervention ICMJE |
|
||||||
Study Arms ICMJE |
|
||||||
Publications * |
|
||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
|||||||
Recruitment Information | |||||||
Recruitment Status ICMJE | Not yet recruiting | ||||||
Estimated Enrollment ICMJE |
120 | ||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||
Estimated Study Completion Date ICMJE | July 1, 2026 | ||||||
Estimated Primary Completion Date | February 1, 2026 (Final data collection date for primary outcome measure) | ||||||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
|
||||||
Sex/Gender ICMJE |
|
||||||
Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||||
Accepts Healthy Volunteers ICMJE | No | ||||||
Contacts ICMJE | |||||||
Listed Location Countries ICMJE | Canada | ||||||
Removed Location Countries | |||||||
Administrative Information | |||||||
NCT Number ICMJE | NCT06174220 | ||||||
Other Study ID Numbers ICMJE | PHRI.TaRGET | ||||||
Has Data Monitoring Committee | Yes | ||||||
U.S. FDA-regulated Product |
|
||||||
IPD Sharing Statement ICMJE |
|
||||||
Current Responsible Party | Hamilton Health Sciences Corporation | ||||||
Original Responsible Party | Same as current | ||||||
Current Study Sponsor ICMJE | Hamilton Health Sciences Corporation | ||||||
Original Study Sponsor ICMJE | Same as current | ||||||
Collaborators ICMJE |
|
||||||
Investigators ICMJE |
|
||||||
PRS Account | Hamilton Health Sciences Corporation | ||||||
Verification Date | February 2024 | ||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |