Fixed dynamometry is more sensitive than vital capacity or ALS rating scale.

Area of Science:

• Neurology
• Biomedical Engineering
• Clinical Trials

Background:

• Developing sensitive outcome measures is crucial for advancing amyotrophic lateral sclerosis (ALS) therapeutics.
• Existing measures like ALSFRS-R and VC have limitations in detecting subtle changes.

Purpose of the Study:

• To compare the sensitivity and variability of the Accurate Test of Limb Isometric Strength (ATLIS) against the ALS Functional Rating Scale-Revised (ALSFRS-R) and vital capacity (VC).
• To evaluate ATLIS's potential for improving the efficiency of ALS clinical trials.

Main Methods:

• A longitudinal study involving 100 participants with ALS.
• Comparison of ATLIS (using a wireless load cell) with ALSFRS-R and VC over multiple visits.
• Analysis of data from 66 participants with complete ATLIS, ALSFRS-R, and VC measurements.

Main Results:

• ATLIS demonstrated significantly less within- and among-person variability compared to ALSFRS-R and VC.
• Participants with normal ALSFRS-R scores exhibited lower-than-expected strength on ATLIS, indicating prefunctional deficits.
• ATLIS detected changes more sensitively than ALSFRS-R or VC.

Conclusions:

• ATLIS is a more sensitive outcome measure for ALS progression than ALSFRS-R or VC.
• Utilizing ATLIS could reduce clinical trial sample size requirements by approximately 33%.
• ATLIS's ability to detect prefunctional changes holds significant value for early-phase ALS drug development.