Résumé :
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ObjectiveWe performed a pilot study with the primary aim to establish the safety, tolerability of a combination of the NO donor isosorbide dinitrate and the non steroid antiinflammatorydrug ibuprofen in a cohort of adult patients affected by muscular dystrophies (Duchenne Muscular dystrophy, DMD, Becker muscular dystrophy, BMD, andLimb-girdle muscular dystrophy, LGMD) MethodsThis safety study of isosorbide dinitrate + ibuprofen included 71 patients, of whom 35 treated with the drug combinationfor 12 months and 36 untreated, each groups consisting of patients affected by DMD, BMD and LGMD.Safety and adverse events were assessed by reported signs andsymptoms, as well as by physical examinations, laboratory results, cardiac and respiratory function tests.Biological activity of the drug combination was assessed throughmotor function measure scale as well as cardiac and respiratory function testing. ResultsOverall, co-administration of isosorbide dinitrate + ibuprofen was associatedwith good safety and tolerability profiles. 7 patients did not complete the study due to very mild side effects or to lack of compliance to the treatment. Analysis of theexploratory end points of muscle strength or function evidenced a trends towards amelioration that reached statistical significance with dimension 1 (D1) and dimension3 (D3) of the MFM (Motor function Measure). Interpretation These preliminary data supports the hypothesis that systemic administration of ibuprofen and isosorbidedinitrate show an adequate safety margin for clinical studies aimed at assessing efficacy.
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