Quantitative strength testing in ALS clinical trials.

Area of Science:

• Neurology
• Clinical Trials
• Biostatistics

Background:

• Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease.
• Accurate and reliable measures are crucial for assessing disease progression and treatment efficacy in ALS clinical trials.

Purpose of the Study:

• To evaluate the utility of quantitative strength testing using hand-held dynamometry (HHD) as an efficacy endpoint in two large Phase 3 ALS trials.
• To assess the reliability and reproducibility of HHD in measuring strength decline in ALS patients.

Main Methods:

• Two double-blind, randomized, placebo-controlled Phase 3 trials (ceftriaxone and dexpramipexole) involving 513 and 943 ALS patients, respectively.
• HHD was used to measure strength in 9 muscle groups bilaterally at regular intervals (every 2-3 months).
• Strength measurements were analyzed individually and as composite megascores; reliability was assessed using the coefficient of variation for rate of change.

Main Results:

• HHD demonstrated reliability and reproducibility in measuring strength decline in ALS.
• While HHD performed slightly less well than the ALSFRS-R, it outperformed vital capacity as a measure of disease progression.
• Individual muscle strength measurements showed high correlation with contralateral sides and other regional muscles.
• Strength decline correlated with both ALSFRS-R and vital capacity, indicating construct validity.

Conclusions:

• Quantitative strength testing with HHD is a reliable and reproducible method for assessing disease progression in ALS.
• HHD shows potential as a valuable efficacy measure in future ALS clinical trials.
• The findings support the integration of HHD into standard ALS outcome assessments.