RECRUITINGPhase 3INTERVENTIONAL

The Efficacy and Safety of Metoprolol as add-on Treatment to Standard of Care in Preventing Cardiomyopathy in Patients With DMD

The Efficacy and Safety of Metoprolol as add-on Treatment to Standard of Care in Preventing Cardiomyopathy in Patients With Duchenne Muscular Dystrophy Aged 8-16 Years. A Randomized, Double-blind, Placebo-controlled Study

About This Trial

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.

Who May Be Eligible (Plain English)

Who May Qualify: - Subject's parent(s) or legal guardian(s) has (have) provided written willing to sign a consent form, 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) - Taking ACEi treatment at minimum required doses for at least 30 days Who Should NOT Join This Trial: - 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 - Clinical signs or symptoms of heart failure - Left ventricular Ejection Fraction (LVEF) \<57% (assessed by Teichholtz echocardiography) - Inability to obtain adequate quality echocardiography images (necessary to monitor for primary endpoint and safety) - Known allergic reactions to components of the IMPs Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language

Inclusion Criteria: * 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) * Taking ACEi treatment at minimum required doses for at least 30 days Exclusion Criteria: * 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 * Clinical signs or symptoms of heart failure * Left ventricular Ejection Fraction (LVEF) \<57% (assessed by Teichholtz echocardiography) * Inability to obtain adequate quality echocardiography images (necessary to monitor for primary endpoint and safety) * Known allergic reactions to components of the IMPs

Treatments Being Tested

DRUG

Metoprolol Succinate

Metoprolol 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.

DRUG

Placebo

Placebo will be in the form of identical tablets and will be administered orally once daily.

Locations (1)

University Clinical Centre in Gdańsk, Clinic of Paediatric Cardiology and Congenital Heart Defects

Gdansk, Pomeranian Voivodeship, Poland