Six-Minute Activity-95^th Centile, a Novel Wearable-Derived Clinical Outcome Assessment for Duchenne Muscular Dystrophy

Background: The six-minute walk test and quantitative muscle testing (QMT) are commonly used skeletal muscle assessments in Duchenne muscular dystrophy; however, they present challenges in nonambulatory patients. Our objective was to evaluate whether 6-min activity-95^th centile, a novel accelerometry metric capturing a participant's greatest amount of movement in six consecutive minutes, distinguished between ambulatory and nonambulatory individuals and correlated with QMT data. Methods: Participants (N = 139) in an observational, longitudinal natural history study with median age of 12.0 years [interquartile range 10.0, 15.0] completed muscle testing and were instructed to wear an accelerometer on dominant wrist for 7 days and nights (a “wear”) at each of three annual study visits. One hundred two male participants were analyzed with a total of 184 valid wear periods. Results: Six-minute activity centiles declined over 2 years (n = 28, P < 0.001). No significant declines in centiles were detected immediately following loss of ambulation (n = 11). Significant correlations were observed between 6-min activity centiles and indexed QMT, with strongest at 95^th centile (r_s = 0.647, P < 0.001). There was a relationship between 6-min centiles and time since loss of ambulation. Conclusions: Ambulatory and nonambulatory patients with Duchenne muscular dystrophy were differentiated by 6-min activity and declined over time, modeling progression of skeletal myopathy. Six-minute activity-95^th centile has potential for future use as an effort-independent outcome of skeletal muscle progression and functional decline for both ambulatory and nonambulatory individuals.