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 five sequential measurements of multiple muscles over a period of 8 months at 2-month intervals using the mView EIM device (Myolex, Inc., San Francisco, CA). 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.

Keywords:

• Electrical impedance myography
• biomarker
• clinical trials
• ALS

Search terms:

• ALS
• electrical impedance myography
• biomarker
• outcomes

Declaration of interest

Drs. Rutkove and Bohorquez hold equity in Myolex, Inc, receive consulting fees from the company and are named as inventors on relevant patents; they also received funding support for this study. All others received funding support only.

Additional information

Funding

This study was funded by SBIR grant (R44NS070385) from the NINDS at the National Institutes of Health to Skulpt Inc. N.B. Skulpt, Inc was renamed Myolex, Inc. in 12/2016.