The Efficacy and Safety of Metoprolol as add-on Treatment to Standard of Care in Preventing Cardiomyopathy in Patients With DMD (MeDMD)
Muscular Dystrophy, Duchenne
About this trial
This is an interventional treatment trial for Muscular Dystrophy, Duchenne
Eligibility Criteria
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
Sites / Locations
- University Clinical Centre in Gdańsk, Clinic of Paediatric Cardiology and Congenital Heart DefectsRecruiting
Arms of the Study
Arm 1
Arm 2
Placebo Comparator
Experimental
Control Group
Treatment Group
Matching placebo will be supplied by the sponsor in child-proof bottles containing dividable tablets with the following dosage of 25mg of IMP and 100mg of IMP. The drug will be administered orally at singular daily doses ranging from 0.75 to 4.5 mg/kg over a Double-Blind Treatment Period (DBTP) of up to 60 months or less dependently on the time of enrolment. The Treatment Period will begin with up to 12-weeks long Up-titration Phase, during which the dose will be gradually escalated. If patient presents with signs and symptoms of intolerance the dose may be temporarily or permanently downgraded at the discretion of the clinician. The up titration ends with reaching maximal tolerated dose level or at a dose corresponding to 4.5 mg/kg.
Metoprolol succinate will be supplied by the sponsor in child-proof bottles containing dividable tablets with the following dosage of 25mg of IMP and 100mg of IMP. The drug will be administered orally at singular daily doses ranging from 0.75 to 4.5 mg/kg over a Double-Blind Treatment Period (DBTP) of up to 60 months or less dependently on the time of enrolment. The Treatment Period will begin with up to 12-weeks long Up-titration Phase, during which the dose will be gradually escalated. If patient presents with signs and symptoms of intolerance the dose may be temporarily or permanently downgraded at the discretion of the clinician. The up titration ends with reaching maximal tolerated dose level or at a dose corresponding to 4.5 mg/kg.