STOCKHOLM – according to research presented at the annual congress of the European Committee for Treatment and Research in MS. Remote gait monitoring using a popular fitness tracker may offer a surrogate measure of MS disability in clinical trials, the researchers reported.
Many outcome measures in MS are evaluated in controlled contexts and do not indicate how patients are functioning outside of the clinical setting, said, from the Weill Institute for Neurosciences at the University of California, San Francisco. Patient-reported outcome measures are subject to recall bias and uneven perception of deficits. Remote ambulatory monitoring, on the other hand, could be a more objective measure that provides continuous information in the real-world setting, said Dr. Block. She and her colleagues have proposed remote ambulatory activity monitoring as an outcome measure for clinical trials.
The investigators chose this measure as an exploratory endpoint for, a phase 3 trial investigating the efficacy and safety of MD1003 (high-dose pharmaceutical-grade biotin) in patients with inactive primary progressive MS and secondary progressive MS. “To our knowledge, this is the first major clinical trial in progressive MS to include continuous remote step count monitoring as an exploratory endpoint,” said Dr. Block.
In the SPI2 study, patients received either MD1003 (300 mg/day) or placebo. To examine the relationship between ambulatory monitoring and clinical disability and MRI measures, the researchers remotely monitored participants’ ambulatory activity for 27 months using a fitness tracker. The investigators used the average daily step count from the first 30 days as the baseline activity measure. At first, they set a low daily step-count goal to minimize the influence of motivation on ambulatory activity. Participants later were taught how to change the goal independently.
Dr. Block and colleagues created LASSO subset selection regression models to correlate average daily step count with sex, age, disease duration, age at onset, disease course, and various MRI models (such as upper cervical cord area, gray matter volume, normalized brain volume, thalamic volume, and T1 and T2 lesion volumes). They performed least squares regression models on the subset selection results. Finally, the researchers calculated Spearman correlations between average daily step count and clinical disability, as measured by Expanded Disability Status Scale (EDSS) and timed 25-foot walk, and the Physical and Mental Health Composite measures of the MS Quality of Life scale (MSQoL-29).
As of April 23, 2019, the researchers had enrolled 492 patients (262 women) with full data at 90 centers (40 in the United States, 39 in Europe, 8 in Canada, and 3 in Australia). In all, 311 patients (63%) had secondary progressive MS, and 181 had primary progressive MS. Participants had moderate disability; the median EDSS score was 6.0. Median disease duration was 10.6 years. The mean daily step count during the first month was 3,699.
Greater step count was correlated with lower EDSS score, faster completion of the timed 25-foot walk, better Physical Health Composite score, better Symbol Digit Modalities Test score, and better Mental Health Composite score. Furthermore, greater mean daily step count also correlated with greater upper cervical cord area, greater normalized brain volume, greater gray matter volume, and lower T1 lesion volume. The correlations between step count and thalamic volume and T2 lesion volume were not significant. “These data support the study of steps as an exploratory outcome measure in clinical trials for progressive MS,” said Dr. Block.
Dr. Block received reimbursement for travel expenses related to this study from MedDay Pharmaceuticals. Coinvestigators received research support and compensation from companies such as Abbvie, Alexion, Biogen, Genentech, MedDay Pharmaceuticals, Novartis, and Sanofi Genzyme. One investigator is an employee of MedDay Pharmaceuticals.
SOURCE: Block V et al. ECTRIMS 2019, .