The study includes 150 patients with DMD diagnosis confirmed by genetic testing, 8-16 years old (≥8 and \<17) at the study entry with a follow-up of up to 5 years. Random enrollment of a patient to one of two groups (intervention or control) takes place after pre-screening and screening stage starts the first phase of the trial. To be eligible for participation in the study, patients must receive standard of care cardiac therapy, which is an Angiotensin-converting-enzyme inhibitor (ACEi) for at least one-month prior to enrollment. A major part of the trial is equal for all patients - who will be receiving indistinguishable investigational medicinal products (IMPs), the drug metoprolol succinate or placebo. As a part of the clinical trial, diagnostic examinations evaluating progression of the disease, will be performed periodically. In addition, all patients will be monitored at home. Heart rate, blood pressure and patients' personal well-being will be controlled using telemedicine technologies. Additional visits in the research center will be provided if any adverse events occur. This model will be continued for 30 months from the enrollment of a first patient. After this period the first drug efficiency analysis will be performed. After that, the intervention may be continued or in case of negative impact of the intervention on patients' health and well-being, terminated with further patients monitoring.
Subject's parent(s) or legal guardian(s) has (have) provided written informed consent, where applicable, prior to any study-related procedures; participants will be asked to give written or verbal assent according to requirements (>16 years old)
Stated willingness to comply with all study procedures and availability for the duration of the study
Ability to take oral medication and be willing to adhere to the study intervention regimen
Subject has confirmed diagnosis of DMD, as defined as clinical picture consistent with typical DMD and: i) Dystrophin immunofluorescence and/or immunoblot showing complete dystrophin deficiency, or ii) Identifiable mutation within the DMD gene (deletion/duplication of one or more exons), where reading frame can be predicted as 'out-of-frame' or, iii) Complete dystrophin gene sequencing showing an alteration (point mutation, duplication, other) that is expected to preclude production of the dystrophin protein (i.e., nonsense mutation, deletion/duplication leading to a downstream stop codon)
Current or previous permanent use of any beta-blocker medication
Treatment with another investigational drug or other intervention within 3 months prior to screening
Clinically significant bradycardia at rest or by Holter ECG, based on age and sex adjusted normal values, atrioventricular block higher than first degree at rest, or second degree Wenckebach at night, pauses longer than 2.5 seconds
Presence of pacemaker or ICD
Parallel
Metoprolol Succinate
DrugMetoprolol Succinate will be in the form of tablets and will be administered orally once daily. The dose will depend on the patient's weight category. Subject should take their treatment at a consistent time each day to promote compliance. IMP will be up titrated. Every two weeks the patients will be given the higher dose of metoprolol succinate or placebo accordingly to scheme.
Placebo
DrugPlacebo will be in the form of identical tablets and will be administered orally once daily.
Change in left ventricular ejection fraction (LVEF %) by Teichholtz method (echocardiography), compared to baseline at Interim Analysis and Final Analysis.
To evaluate whether metoprolol succinate in addition to standard of care treatment compared to placebo in children with DMD delays the progression of LV function loss.
DFS (the time to develop clinically evident heart failure)
To evaluate whether metoprolol succinate in addition to standard of care treatment compared to placebo in children with DMD delays progression of cardiomyopathy and heart failure
Prevalence of patients with myocardial fibrosis assessed by LGE Cardiac magnetic resonance (CMR)
To evaluate whether metoprolol succinate in addition to standard of care treatment compared to placebo in children with DMD delays progression of LGE in CMR
Prevalence of patients with sinus tachycardia based on resting HR (ECG) or defined as mean daily heart rate above 95th percentile for age and sex
To evaluate whether metoprolol succinate in addition to standard of care treatment compared to placebo in children with DMD prevents sinus tachycardia commonly seen in DMD patients
The rate of AE and SAE
To assess the safety and tolerability of metoprolol succinate in children with DMD
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