Longitudinal Study Comparing the Responsiveness of Outcomes Measures in ALS Trials

Confidential Human Trial Longitudinal Study Comparing the Responsiveness of Outcomes Measures in ALS Trials Statement of Work Abstract A clear unmet challenge in ALS clinical research is the ability to screen potential therapeutic agents quickly. Using more sensitive and accurate outcome measures may improve clinical trial efficiency, requiring fewer subjects during a shorter time period. Quantitative strength measures accurately reflect disease progression in ALS. However, current methods are either very expensive and inconvenient or are unable to accurately measure strength throughout the entire strength range. We developed a new device, Accurate Test of Isometric Strength (ATLIS) that is easy to use and accurately tests strength of strong and weak muscle groups with high reliability. The maximal force of 12 muscle groups in the arms and legs are tested using fixed, wireless load cells and a high-back, adjustable chair. Raw scores are converted to percent of predicted normal to allow accurate comparisons between persons. Establishing a disease progression rate for each individual will allow us to detect small but clinically relevant therapeutic effects. This project will compare use of normalized ATLIS data with ALS-Functional Rating Scale-Revised and vital capacity (VC) in a prospective, longitudinal study of 100 subjects tested approximately every 2 to 4 months at four clinical sites. The study will determine the relative sensitivity of these 3 outcomes measures to define disease progression. The hypothesis is that ATLIS data will have significantly less variance than ALSFRS-R and VC data around each subject's regression slope.