E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Duchenne muscular dystrophy is an X-linked inherited disorder which primarily affects skeletal muscle through a mutation in dystrophin which maps to the long arm of the X chromosome (Xp21). Patients with skeletal myopathy such as DMD eventually progress to develop dilated cardiomyopathy as dystrophin is expressed in all forms of muscle including cardiac and smooth muscle. Often the cause of death in patients with DMD is cardiac failure and arrhythmia. |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
1.Determine baseline left ventricular systolic function using cardiac MRI, neurohormonal status (B natriuretic peptide levels, secreted by ventricular myocardium in congestive heart failure), two-dimensional echocardiographic and tissue Doppler imaging characteristics of a cohort of patients (children / adolescents 7-18 years age) with DMD.
2.Determine the effects of carvedilol on LV ejection fraction, LV end-diastolic and systolic volumes, BNP levels, and tissue Doppler imaging velocities. The effects on these parameters (LV dimensions, LVEF, tissue Doppler velocities) will be measured at baseline and at 6 months after commencing therapy. The effects on BNP levels will be assessed at baseline, 1 and 6 months after initiation of therapy.
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Diagnosis of confirmed DMD with either dilated LV (>2Z scores) and depressed LV systolic function (LVEF <40%).
2.Agreement to participate.
3.Patients already treated with afterload reduction (ACE inhibitors), digitalis or diuretics will not be excluded as they will act as their own controls in determining positive or negative effects of carvedilol.
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E.4 | Principal exclusion criteria |
1.Refusal to participate. 2.Severe asthma which would be exacerbated by beta-blockade 3.Glucose intolerance or diabetes mellitus. 4.Severe claustrophobia which would prevent MR. 5.Any major contra-indication to cardiac MRI
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Left ventricular ejection fraction. 2. Left ventricular shortening fraction. 3. Left ventricular end diastolic and systolic volumes. 4. Tissue Doppler velocities. 5. BNP levels. 6. Clinical improvement of symptoms (NYHA status) and signs of heart failure. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The study will be terminated after patients have been treated for six months. Should patients develop severe side effects to the medication then the patient will be withdrawn from the study. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |