Abstract
Introduction
Duchenne muscular dystrophy (DMD) is a life-limiting disease characterized by progressive muscle wasting of skeletal and cardiac myocytes. Nowadays, heart failure is the principal cause of death. Current treatment is still unsatisfactory. Empagliflozin has shown excellent results in adults with heart failure, and is licensed for adolescents > 10 years of age with type 2 diabetes mellitus. In an effort to repurpose empagliflozin for DMD-associated cardiomyopathy, we aim to describe its pharmacokinetic behaviour in this population, assess ease-of-swallow, monitor safety, explore efficacy and screen efficacy markers.Methods
This is a single-arm, single-centre, open-label phase 2a trial in children and adolescents aged 6 to ≤ 18 years with DMD-associated cardiomyopathy. Participants (n = 12) will take empagliflozin 10 mg once daily for 6 months, with a whole-day stay at visit 1 for the evaluation of pharmacokinetics, and follow-up visits at 1 week, 6 weeks, 3 months and 6 months. On top of acceptability (ease-of-swallow), which will be assessed at visit 1, further secondary endpoints include safety and efficacy clinical (e.g. heart rate, blood pressure), biochemical (e.g. NT-proBNP, haemoglobin, uric acid, electrolytes, renal function), imaging (echocardiography, cardiac magnetic resonance) and bioimpedance (intra- and extracellular fluid volume) parameters.Planned outcomes
Characterization of primary and secondary pharmacokinetic parameters will allow one to define the dose range for children and adolescents with DMD-associated cardiomyopathy, informing both current compassionate care and the design of future efficacy trials. Additionally, this trial will enable the identification of efficacy markers to be used as endpoints in future efficacy trials and in clinical practice.Trial registration number
NCT06643442, ISRCTN 12497973, IRAS number 1009946.