Reducing sample size requirements for future ALS clinical trials with a dedicated electrical impedance myography system

Abstract

Objective: In this longitudinal multicenter cohort study, we evaluated the potential of a dedicated electrical impedance myography (EIM) device to assess ALS progression and the system’s basic reproducibility and diagnostic accuracy. Methods: Forty-six ALS patients underwent up to 5 sequential measurements of multiple muscles over a period of 8 months at 2-month intervals using the mView EIM device (Myolex, Inc). Standard measures of disease status were also obtained. A group of 30 healthy volunteers and 30 ALS-mimics were evaluated once to determine if the technique could assist with initial diagnosis. Several electrode arrays and EIM outcomes were assessed. Results: EIM tracked ALS progression; power analyses suggested a 5.2-fold reduction in sample size requirements compared to ALSFRS-R by utilizing 50 kHz phase value from the muscle with the greatest EIM decline in each subject. This progression rate correlated to total ALSFRS-R progression, with R=0.371, p=0.021. Reproducibility was high, with both intra- and inter-rater intraclass correlation coefficients for individual muscles mostly greater than 0.90. The mean 50 kHz phase distinguished between ALS patients and healthy controls (area-under-curve 0.78, 95% confidence intervals (CIs) 0.68,0.89), but not between mimics and ALS patients (area-under-curve 0.60, 95% CIs 0.47,0.73). Conclusions: While limited in its specificity to identify ALS versus disease mimics, these results support the hypothesis that single-muscle EIM can serve as a convenient, repeatable, and powerful outcome measure in ALS clinical trials.

Partial Weight-Bearing in Female Rats: Proof of Concept in a Martian-Gravity Analog

“…EIM is finding increasing value for the assessment of muscle health in humans (Tarulli et al, 2005;Rutkove et al, 2017;Shefner et al, 2018). In a few seconds, localized impedance measurements can be obtained and include resistance (R) and reactance (X).…”

Functional Biomarkers for Amyotrophic Lateral Sclerosis

“…The advantage is that this technique does not rely on inherent electrical activity of the tissue (which conventional neurophysiological techniques do), but rather on how the tissue impacts the applied current, rendering the technique sensitive to structural and compositional changes in muscle such as denervation, reinnervation, myofiber atrophy and fat replacement within the muscle that occur in ALS (104). EIM values have been shown to correlate with standard clinical approaches including handheld dynamometry and MUNE (106, 107), and may be able to provide more than a five-fold reduction in sample size requirements for ALS clinical therapeutic trials over standard outcome measures such as the ALS functional rating scale-revised (ALSFRS-R) (108). Although EIM can detect changes early in the disease course of ALS as well as in clinically unaffected muscle groups (105), a limitation of EIM is that identified changes may not be able to differentiate ALS from other neuromuscular conditions (109, 110).…”

Point of Care Quantitative Assessment of Muscle Health in Older Individuals: An Investigation of Quantitative Muscle Ultrasound and Electrical Impedance Myography Techniques

“…Impedance is not very high in healthy muscle but is known to increase in conditions that impact normal muscle architecture [13]. Prior studies in amyotrophic lateral sclerosis (ALS) and Duchenne muscular dystrophy (DMD) demonstrate the promise of this technique [14,15,16]. Unlike imaging studies, EIM can be performed with little training.…”