Duchenne muscular dystrophy

Multicentric, national, randomized, placebo-controlled, double-blind, Phase III

130 male patients between the ages of 10 and 14-years-old with verified Duchenne muscular dystrophy

• Inclusion of the last patient (randomized): June 2012
• Final examination of the last patient (LPLV): 4th Quarter of 2015
• Financing by the BMBF (German Federal Ministry for Education, Science, Research and Technology) for 6 years

Goal of this study is to find out whether a preventive therapy with the ACE inhibitor enalapril and the beta-blocker metoprolol can serve to delay the start of a cardiac insufficiency and thereby lead to an improved quality of life as well as to a prolonged survival rate in patients with a known Duchenne muscular dystrophy. The primary target criterion for evaluating the efficacy of prophylactic anticongestive therapy is the time from randomization until the development of a left-ventricular dysfunction, which is defined as a left ventricular shortening fraction (LVSF), as seen in the 2D echocardiography, of < 28%.

• Compare the safety and tolerance
• Compare the quality of life using the Kindl questionnaire
• Compare the diagnostic advantages/disadvantages to the use of a tissue Doppler as compared with 2D echocardiography
• Compare the total survival time in the two study arms
• Compare pathophysiological changes in the neuromuscular feedback system
• Compare reduction in heart rate and heart frequency variability

• written declaration of consent of the guardian and agreement of the patient
• male, 10-14-years-old (completed years)
• diagnosis of Duchenne muscular dystrophy (molecular-genetic and/or through a muscle biopsy)
• normal left ventricular shortening fraction (LVSF ≥ 30%), as measured via echocardiography
• no previous treatment with ACE inhibitors, beta-blockers or AT II receptor antagonists during the last 3 months
• patient capable of performing the routine visits
• patient capable of regularly taking the medication
• patient is available for follow-ups (data collection during the course of the study)
• at least the initial dose of the study medication is tolerated (randomization criterion)

• participation in another clinical study at the same time
• previous therapy with ACE inhibitors, beta-blockers or AT II receptor antagonists during the last 3 months
• dilated left ventricle (> 97th percentile)
• intolerance or contraindication to the study medication
• limited renal function (GFR < 30 ml/min/ 1.73 m2)
• disturbed liver function (γ-GT and bilirubin with double the normal value)
• other medical grounds which are indicative against participation in the study
• patient is not capable of following the study protocol   

• Not permitted: Concomitant administration of beta-blockers or ACE inhibitors, other than the study medication, angiotensin II receptor antagonists, medications which may be expected to interact with the study medication (see expert information).
• Permitted: Steroid therapy (e.g., prednisolone), immunosuppressive therapy, non-steroidal concomitant medication begun 3 months prior to the start of the study (vitamin E, creatine monohydrate, green tea extract)

A maximum of 17 visits over the course of six years (depending on the time at which the primary endpoint is reached and the time of enrollment of the patient)

Course of the study:

• Open run-in phase to determine the dose (1st – 4th month)
  
• Blinded treatment phase (5th month – 6th year of the study)
  
• Follow-up phase / treatment according to the guidelines

2,230 EUR/patient

A number of clinics and heart centres all over Germany are taking part in the study. An up-to-date list of these participants can be found here …