Effect and Safety of preventive Treatment with ACE-Inhibitor and Beta-Blocker on the onset of Left Ventricular Dysfunction in Duchenne Muscular Dystrophy

INTERVENTION: Trade Name: EnalHexal®, 5 mg Pharmaceutical Form: Tablet INN or Proposed INN: ENALAPRIL CAS Number: 75847733 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 5‐ Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use Trade Name: EnaHexal®, 10mg Pharmaceutical Form: Tablet INN or Proposed INN: ENALAPRIL CAS Number: 75847733 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 10‐ Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use Trade Name: MetoHEXAL® Succ ® 23,75 mg Retardtabletten Pharmaceutical Form: Tablet INN or Proposed INN: METOPROLOL SUCCINATE CAS Number: 98418474 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 23.75‐ Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use Trade Name: MetoHEXAL® Succ ® 47,5 mg Retardtabletten Pharmaceutical Form: Tablet INN or Proposed INN: METOPROLOL SUCCINATE CAS Number: 98418474 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 47.5‐ Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use Trade Name: MetoHEXAL® Succ ® 95 mg Retardtabletten Pharmaceutical Form: Tablet INN or Proposed INN: METOPROLOL SUCCINATE CAS Number: 98418474 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 95‐ Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use CONDITION: Therapeutic area: Diseases [C] ‐ Musculoskeletal Diseases [C05] PRIMARY OUTCOME: Main Objective: Efficacy of prophylactic anticongestive therapy: time from randomisation to left ventricular dysfunction, defined as left‐ventricular shortening fraction <28%(6 monthly control visits) Primary end point(s): efficacy of prophylactic anticongestive therapy, time from randomisation to left ventricular dysfunction,defined as left‐ventricular shortening fraction < 28% (6 monthly control visits) Secondary Objective: ‐ Comparison of safety and tolerability; ‐ Comparison of quality of life (Kindl questionnaire12‐16) ; ‐ Comparison of diagnostics: Tissue Doppler vs 2D Echocardiography; ‐ Comparison of total survival in both arms ; ‐ Comparison of pathophysiological changes in neuromuscular regulation (neurohumeral parameters like pro‐ BNP, Angiotensin II, Noradrenalin); ‐ Comparison of drop of heart frequency rate and heart frequency variability (24h ECG, Tissue Doppler); ; Timepoint(s) of evaluation of this end point: from baseline R4 until study end SECONDARY OUTCOME: Secondary end point(s): comparison of safety and tolerability; comparison of quality of life (Kindl); comparison of diagnostics tissue doppler vs 2 D Echo; comparison of pro‐BNP, Angiotensin II, Noradrenalin Timepoint(s) of evaluation of this end point: change of LVSF from baseline INCLUSION CRITERIA: Male patients with DMD (confirmed by genetic analysis or muscle biopsy) • aged 10 – 14 years • Normal left ventricular function (fraction shortening = 30%) • Normal renal function (GFR > 30 ml/min/1,73 m2) • Informed Consent of both parents, assent of patient Are the trial subjects under 18? yes Number of subjects for this age range: 55 F.1.2 Adults (18‐64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range