Electrical impedance myography as a biomarker to assess ALS progression

Abstract

Electrical impedance myography (EIM), a non-invasive, electrophysiological technique, has preliminarily shown value as an ALS biomarker. Here we perform a multicenter study to further assess EIM’s potential for tracking ALS. ALS patients were enrolled across eight sites. Each subject underwent EIM, handheld dynamometry (HHD), and the ALS Functional Rating Scale-revised (ALSFRS-R) regularly. Techniques were compared by assessing the coefficient of variation (CoV) in the rate of decline and each technique’s correlation to survival. Results showed that in the 60 patients followed for one year, EIM phase measured from the most rapidly progressing muscle in each patient had a CoV in the rate of decline of 0.62, compared to HHD (0.82) and the ALSFRS-R (0.74). Restricting the measurements to the first six months gave a CoV of 0.55 for EIM, 0.93 for HHD, and 0.84 for ALSFRS-R. For both time-periods, all three measures correlated with survival. Based on these data, a six-month clinical trial designed to detect a 20% treatment effect with 80% power using EIM would require only 95 patients/arm compared to the ALSFRS-R, which would require 220 subjects/arm. In conclusion, EIM can serve as a useful ALS biomarker that offers the prospect of greatly accelerating phase 2 clinical trials.

Key words::

• Clinical trials
• amyotrophic lateral sclerosis
• electrical impedance myography

Acknowledgements

This study was funded by the ALS Association. We thank Lindsay Garmirian, Connie Lin, Philip Mongiovi, Lucy Wang, Tuhin Srivastava, and Andrew Spieker for their assistance with this project.

Declaration of interest: S. B. Rutkove serves as a consultant and holds equity in Convergence Medical Devices, Inc. He has also receives consulting fees from Neuralstem, Inc., GlaxoSmithKline, Inc. and royalties from UpToDate. He also has two patent applications submitted in the field of electrical impedance. He receives grant funding from NIH, NASA, and the Spinal Muscular Atrophy Foundation. J. B. Caress receives grant funding from NIH.

M. S. Cartwright receives grant funding from NIH. T. Burns serves as Podcast Section Editor for Neurology®; has served as a consultant for Bayhill Therapeutics; and has received research support from Knopp Neurosciences Inc. and the Myasthenia Gravis Foundation of America.

N. Maragakis serves on a scientific advisory board for Q Therapeutics, Inc.; received support from the Michael S. Ansari Gift Fund for basic science research; serves as a contributor to UpToDate; has served as a consultant for California Institute for Regenerative Medicine (CIRM); and receives/has received research support from Cytokinetics Inc., Sangamo BioSciences, Inc., TEDCO-Maryland Stem Cell Research Fund, NIH/NINDS, U.S. Department of Defense, and the ALS Association Packard Center for ALS Research at Johns Hopkins. M. Benatar has served as a consultant for Bayhill Therapeutics and Cytokinetics Inc.; receives publishing royalties for Neuromuscular Disease: Evidence and Analysis in Clinical Neurology (Humana Press, 2006), BluePrints in Neurology (Lippincott Williams & Wilkins, 2002), and Field of Vision: A Manual and Atlas of Perimetry (Humana Press, 2010); receives/has received research support from CytRx Corporation, the Muscular Dystrophy Association, the ALS Association, the Food and Drug Administration, and the Centers for Disease Control and Prevention, theWoodruff Health Sciences Center (Emory University), and the NIH; and has participated in medico-legal cases. J. M. Shefner serves on a DSMB for the NIH; serves as Neuromuscular Section Editor for and receives publishing royalties from UpToDate; has served as a consultant for Teva Pharmaceutical Industries Ltd., Gilead Sciences, Inc., GlaxoSmithKline, Trophos, and BrainGate; and receives research support from Isis Pharmaceuticals, Inc., Neuralstem, Inc., GlaxoSmithKline, Sanofi-Aventis, Teva Pharmaceutical Industries Ltd., Knopp Neurosciences Inc., Cytokinetics Inc., the NIH, and the ALS Association.

The authors alone are responsible for the content and writing of the paper.