Delayed onset of ambulation in boys with Duchenne muscular dystrophy: Potential use as an endpoint in clinical trials

摘要

Individuals with Duchenne muscular dystrophy (DMD) often exhibit delayed motor and cognitive development, including delayed onset of ambulation. Data on age when loss of independent ambulation occurs are well established for DMD; however, age at onset of walking has not been well described. We hypothesize that an effective medication given in early infancy would advance the age when walking is achieved so that it is closer to age-matched norms, and that this discrete event could serve as the primary outcome measure in a clinical trial. This study examined three data sets, Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet); Dutch Natural History Survey (DNHS); and Parent Project Muscular Dystrophy (PPMD). The distribution of onset of ambulation in DMD (mean ± SD) and median age, in months, at the onset of ambulation was 17.3 (±5.5) and 16.0 in MD STARnet, 21.8 (±7.1) and 20.0 in DNHS, and 16.1 (±4.4) and 15 in PPMD. Age of ambulation in these data sets were all significantly later (P < 0.001) than the corresponding age for typically developing boys, 12.1 (±1.8). A hypothetical clinical trial study design and power analyses are presented based on these data.