Progressive loss of ambulation is one of the main causes of disability in Amyotrophic Lateral Sclerosis (ALS). A novel digital endpoint, the 95th centile of stride velocity (SV95C), measured by a magneto-inertial device specifically designed for continuous assessment of patients with neurological diseases (ActiMyo®) in uncontrolled environment, has been qualified as a primary endpoint in ambulant Duchenne Muscular Dystrophy, by the European Medicines Agency and is currently considered by the FDA. We conducted a longitudinal multisite natural history study in ALS to determine the feasibility, reliability, external validity and the sensitivity to change of SV95C in non-controlled environment in ambulant individuals with ALS.
Participants were assessed with standard evaluations including the ALS functional rating scale, six-minute walk test, Medical Research Council scores (MRC-S), Ashworth score and hand dynamometer every 3 months for 1 year. After each visit, patients were asked to wear for a month one inertial sensor at the ankle and one sensor at the wrist for continuous assessment of motor function in the real-world setting. These data are compared with already acquired normative data in healthy age-matched control subjects.
We included 19 patients with ALS (6 females and 13 males) aged from 20 to 70 years old. Eighteen of them (94%) provided a recording period over 50 hours at baseline. On the first 8 patients aged from 44 to 68 years old, reliability was excellent with an intra-class correlation coefficient of 0.98. Correlation with MRC-S was 0.46 (p<0.05). All patients declined rapidly with a standardized response mean of -2.78 at 3 months and -2.63 at 6 months. We will present the entire set of data during the congress.
If confirmed on the entire cohort, these data demonstrate the excellent analytical properties of SV95C in ALS, which allows to consider short clinical trials with limited number of patients.