Résumé :
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Objective - To evaluate efficacy and tolerability of treatment with SNT-MC17/idebenone compared to placebo in children with Duchenne muscular dystrophy (DMD). Background - Idebenone supports mitochondrial respiratory chain function and reduces oxidative stress, pathways that are involved in DMD pathogenesis. In a controlled study we have shown that presymptomatic-initiated and long-term treatment with SNT-MC17/idebenone is cardioprotective and improves exercise performance in the homologous dystrophin-deficient mdx mouse. Design/Methods - 21 DMD patients (8-16 yr) with cardiac dysfunction were enrolled in a phase II double-blind randomized placebo-controlled trial. Comedication with glucocorticoids was allowed at stable dosage; use of ACE-inhibitors was excluded. Thirteen patients received SNT-MC17 (450 mg daily) for 52 weeks, 8 patients were randomized to the placebo group. The primary endpoint was the change from baseline in peak systolic radial strain of the left ventricular (LV) inferolateral wall, the region of the heart which is most affected in DMD. Secondary outcome measures included other cardiac parameters, respiratory function and upper limb muscle strength tests. Results - All subjects completed the study, and SNT-MC17 showed good safety and tolerability. Compared to patients on placebo, patients on SNT-MC17 showed significant improvement in peak systolic radial strain of the LV inferolateral wall (p= 0.030). Peak systolic longitudinal strain of the LV lateral wall improved in patients on SNT-MC17 and deteriorated in patients on placebo (p=0.039). Whereas SNT-MC17 treatment was associated with improvement in respiratory peak flow, patients on placebo deteriorated (p= 0.039). Changes in forced vital capacity and maximal inspiratory pressures were not statistically significant between the groups. No significant differences were detected for quantitative upper limb muscle strength. Conclusions - This is the first indication of clinical efficacy with SNT-MC17/idebenone on functional cardiac and respiratory parameters in DMD. The results provide the basis and guidance for phase II/III studies with SNT-MC17/idebenone in DMD.
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