Objective
Arrhythmogenic cardiomyopathy (ACM) is an inherited heart problem where the heart muscle is replaced by fibrous and potentially fatty tissue, putting people at risk of dangerous fast heartbeats, sudden cardiac death, and heart failure. The purpose of the TaRGET study is to determine if tideglusib, compared to placebo, will reduce the average number of PVCs per 24 hours in ACM patients.
Background
The most common subtype of ACM mainly involves the right ventricle and is called arrhythmogenic right ventricular cardiomyopathy (ARVC). Both genetics and environmental factors such as exercise can play a role in causing ACM. The standard treatment is placement of an implantable cardioverter defibrillator (ICD), which can deliver a shock when a dangerous rhythm develops, often combined with anti-arrhythmic drugs. However, these medicines do not address the underlying heart muscle problem, which continues to progress. Tideglusib is a new type of drug that has shown promise in treating myotonic dystrophy, and this study investigates whether it can reduce the arrhythmia burden in ACM.
Study Outcomes
Primary
- Show that tideglusib reduces mean PVCs per 24 hours on 7-day Holter monitoring compared to placebo at 6 months of treatment
Secondary
- Show improvement in ventricular strain on echocardiography
- Show reduction in the frequency of ICD therapies (shocks or anti-tachycardia pacing)
- Show reduction in the frequency of sustained ventricular tachycardia
Eligibility Criteria
The criteria below are a summary. Your study doctor will confirm whether this study is right for you.
Inclusion Criteria
- Age ≥ 18 years
- A pathogenic or likely pathogenic desmosomal (PKP2, DSG2, DSC2, DSP, or JUP) rare variant OR the TMEM43-p.S358L variant
- Mean ≥ 500 PVCs per 24 hours on a baseline screening 7-day Holter monitor
- Clinical ACM diagnosis or recognition of genetic carrier status for ≥ 6 months prior to randomization
Exclusion Criteria
- NYHA class IV heart failure
- Ventricular scar secondary to coronary artery disease
- Initiation, cessation, or dose change of a Class I or III anti-arrhythmic drug in the 3 months prior to screening
- Any potentially harmful chronic liver disease, ALT > 2× ULN, or elevated total bilirubin (with exceptions for Gilbert's syndrome)
- A history of alcohol or illicit substance use disorders
- Regular long-term use of strong CYP3A4 inhibitors
- Serum creatinine > 150 µmol/L or creatinine clearance ≤ 60 mL/min at screening
- Pregnancy, or women/men of childbearing potential not using effective contraception
- Patients unwilling to provide informed consent or comply with follow-up
- Hypersensitivity to tideglusib or any of its components, including allergy to strawberry
About taking part
If you would like to learn more about taking part in this study, please contact our research team using the details on this page. We can walk you through what participation involves and answer any questions.