Clinically meaningful change on the 100 meter timed test in neuromuscular diseases (S33.003)

Objective: The purpose of our study was to establish the minimal detectable change (MDC) of the 100m in muscular dystrophies to better interpret results over time and evaluate its utility to predict loss of ambulation. Background: The 100 meter timed test (100m) is a fixed distance ambulatory assessment used to quantify maximal ambulatory ability in children and adults. Subjects are encouraged to run, if safe, to achieve their fastest time. Change in ambulatory ability is a clinically meaningful outcome used across clinical trials for children and adults. A shorter, fixed distance test allowing maximal performance has the potential to reduce variability in performance over time. Design/Methods: Subjects with Duchenne muscular dystrophy (DMD) or a limb girdle muscular dystrophy (LGMD) completed the 100m during at least 1 study visit. The time to complete the test was recorded and a percent predicted was calculated based on age, gender, and body mass index. Results: The DMD cohort included 160 boys (mean age: 7.3 +/− 2.5 years, range 3.4 to 14.7 years) and LGMD cohort included 85 subjects (mean age: 19.6 +/− 11.6 years, range 2.9 to 54.4 years). A subset (N=71 DMD; N= 28 LGMD) completed the 100m up to 3 years post baseline. The MDC for the 100m was calculated as 1/3 the standard deviation of baseline values as well as the standard error of measurement (SEM) approach. Using the MDC 60% of our longitudinal cohort demonstrated a significant decline in ambulation over 12 months. A 100m time of less than 115 seconds, or 25% of predicted, emerged as a critical value for predicting loss of ambulation in DMD. Differences in the effect of LGMD subtype on trajectory of 100m will be discussed. Conclusions: The 100 meter timed test can be implemented in both pediatric and adult populations and can measure meaningful changes over time. Disclosure: Dr. Alfano has nothing to disclose. Dr. Miller has nothing to disclose. Dr. Iammarino has nothing to disclose. Dr. Moore-Clingenpeel has nothing to disclose. Dr. Dugan has nothing to disclose. Dr. Tsao has nothing to disclose. Dr. Rodino-Klapac has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Myonexus Therapeutics, Inc. Dr. Rodino-Klapac has received compensation for serving on the Board of Directors of Myonexus Therapeutics, Inc. Dr. Rodino-Klapac has received royalty, license fees, or contractual rights payments from Myonexus Therapeutics, Inc. and Sarepta Therapeutics.. Dr. Rodino-Klapac holds stock and/or stock options in Myonexus Therapeutics, Inc., which sponsored research in which Dr. Rodino-Klapac was involved as an investigator. Dr. Rodino-Klapac has received research support from Sarepta Therapeutics.. Dr. Waldrop has nothing to disclose. Dr. Flanigan has nothing to disclose. Dr. Mendell has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AveXis, Inc. Dr. Lowes has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AveXis, Inc., Bristol Meyers-Squibb, Pfizer, and Sarepta Therapeutics. Dr. Lowes has received research support from Novartis and Sarepta Therapeutics.