Objectively Monitoring Amyotrophic Lateral Sclerosis Patient Symptoms During Clinical Trials With Sensors: Observational Study (Preprint)
Garcia-Gancedo L., Kelly ML., Lavrov A., Parr J., Hart R., Marsden R., Turner MR., Talbot K., Chiwera T., Shaw CE., Al-Chalabi A.
<sec> <title>BACKGROUND</title> <p>Objective symptom monitoring of patients with Amyotrophic Lateral Sclerosis (ALS) has the potential to provide an important source of information to evaluate the impact of the disease on aspects of real-world functional capacity and activities of daily living in the home setting, providing useful objective outcome measures for clinical trials.</p> </sec> <sec> <title>OBJECTIVE</title> <p>This study aimed to investigate the feasibility of a novel digital platform for remote data collection of multiple symptoms—physical activity, heart rate variability (HRV), and digital speech characteristics—in 25 patients with ALS in an observational clinical trial setting to explore the impact of the devices on patients’ everyday life and to record tolerability related to the devices and study procedures over 48 weeks.</p> </sec> <sec> <title>METHODS</title> <p>In this exploratory, noncontrolled, nondrug study, patients attended a clinical site visit every 3 months to perform activity reference tasks while wearing a sensor, to conduct digital speech tests and for conventional ALS monitoring. In addition, patients wore the sensor in their daily life for approximately 3 days every month for the duration of the study.</p> </sec> <sec> <title>RESULTS</title> <p>The amount and quality of digital speech data captured at the clinical sites were as intended, and there were no significant issues. All the home monitoring sensor data available were propagated through the system and were received as expected. However, the amount and quality of physical activity home monitoring data were lower than anticipated. A total of 3 or more days (or partial days) of data were recorded for 65% of protocol time points, with no data collected for 24% of time points. At baseline, 24 of 25 patients provided data, reduced to 13 of 18 patients at Week 48. Lower-than-expected quality HRV data were obtained, likely because of poor contact between the sensor and the skin. In total, 6 of 25 patients had mild or moderate adverse events (AEs) in the skin and subcutaneous tissue disorders category because of skin irritation caused by the electrode patch. There were no reports of serious AEs or deaths. Most patients found the sensor comfortable, with no or minimal impact on daily activities.</p> </sec> <sec> <title>CONCLUSIONS</title> <p>The platform can measure physical activity in patients with ALS in their home environment; patients used the equipment successfully, and it was generally well tolerated. The quantity of home monitoring physical activity data was lower than expected, although it was sufficient to allow investigation of novel physical activity end points. Good-quality in-clinic speech data were successfully captured for analysis. Future studies using objective patient monitoring approaches, combined with the most current technological advances, may be useful to elucidate novel digital biomarkers of disease progression.</p> </sec>