Electrical impedance myography as a biomarker to assess ALS progression

Seward B. Rutkove, James B. Caress, Michael S. Cartwright, Ted M. Burns, Judy Warder, William S. David, Namita Goyal, Nicholas J. Maragakis, Lora Clawson, Michael G Benatar, Sharon Usher, Khema R Sharma, Shiva Gautam, Pushpa Narayanaswami, Elizabeth M. Raynor, Mary Lou Watson, Jeremy M. Shefner

Research output: Contribution to journalArticle

87 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)439-445
Number of pages7
JournalAmyotrophic Lateral Sclerosis
Volume13
Issue number5
DOIs
StatePublished - Sep 1 2012

Fingerprint

Myography
Electric Impedance
Biomarkers
Clinical Trials
Survival
Multicenter Studies
Muscles

Keywords

  • Amyotrophic lateral sclerosis
  • Clinical trials
  • Electrical impedance myography

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Rutkove, S. B., Caress, J. B., Cartwright, M. S., Burns, T. M., Warder, J., David, W. S., ... Shefner, J. M. (2012). Electrical impedance myography as a biomarker to assess ALS progression. Amyotrophic Lateral Sclerosis, 13(5), 439-445. https://doi.org/10.3109/17482968.2012.688837

Electrical impedance myography as a biomarker to assess ALS progression. / Rutkove, Seward B.; Caress, James B.; Cartwright, Michael S.; Burns, Ted M.; Warder, Judy; David, William S.; Goyal, Namita; Maragakis, Nicholas J.; Clawson, Lora; Benatar, Michael G; Usher, Sharon; Sharma, Khema R; Gautam, Shiva; Narayanaswami, Pushpa; Raynor, Elizabeth M.; Watson, Mary Lou; Shefner, Jeremy M.

In: Amyotrophic Lateral Sclerosis, Vol. 13, No. 5, 01.09.2012, p. 439-445.

Research output: Contribution to journalArticle

Rutkove, SB, Caress, JB, Cartwright, MS, Burns, TM, Warder, J, David, WS, Goyal, N, Maragakis, NJ, Clawson, L, Benatar, MG, Usher, S, Sharma, KR, Gautam, S, Narayanaswami, P, Raynor, EM, Watson, ML & Shefner, JM 2012, 'Electrical impedance myography as a biomarker to assess ALS progression', Amyotrophic Lateral Sclerosis, vol. 13, no. 5, pp. 439-445. https://doi.org/10.3109/17482968.2012.688837
Rutkove SB, Caress JB, Cartwright MS, Burns TM, Warder J, David WS et al. Electrical impedance myography as a biomarker to assess ALS progression. Amyotrophic Lateral Sclerosis. 2012 Sep 1;13(5):439-445. https://doi.org/10.3109/17482968.2012.688837
Rutkove, Seward B. ; Caress, James B. ; Cartwright, Michael S. ; Burns, Ted M. ; Warder, Judy ; David, William S. ; Goyal, Namita ; Maragakis, Nicholas J. ; Clawson, Lora ; Benatar, Michael G ; Usher, Sharon ; Sharma, Khema R ; Gautam, Shiva ; Narayanaswami, Pushpa ; Raynor, Elizabeth M. ; Watson, Mary Lou ; Shefner, Jeremy M. / Electrical impedance myography as a biomarker to assess ALS progression. In: Amyotrophic Lateral Sclerosis. 2012 ; Vol. 13, No. 5. pp. 439-445.
@article{1b146cdbe07145acb4cbc3b79bce2e91,
title = "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.",
keywords = "Amyotrophic lateral sclerosis, Clinical trials, Electrical impedance myography",
author = "Rutkove, {Seward B.} and Caress, {James B.} and Cartwright, {Michael S.} and Burns, {Ted M.} and Judy Warder and David, {William S.} and Namita Goyal and Maragakis, {Nicholas J.} and Lora Clawson and Benatar, {Michael G} and Sharon Usher and Sharma, {Khema R} and Shiva Gautam and Pushpa Narayanaswami and Raynor, {Elizabeth M.} and Watson, {Mary Lou} and Shefner, {Jeremy M.}",
year = "2012",
month = "9",
day = "1",
doi = "10.3109/17482968.2012.688837",
language = "English",
volume = "13",
pages = "439--445",
journal = "Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration",
issn = "2167-8421",
publisher = "Informa Healthcare",
number = "5",

}

TY - JOUR

T1 - Electrical impedance myography as a biomarker to assess ALS progression

AU - Rutkove, Seward B.

AU - Caress, James B.

AU - Cartwright, Michael S.

AU - Burns, Ted M.

AU - Warder, Judy

AU - David, William S.

AU - Goyal, Namita

AU - Maragakis, Nicholas J.

AU - Clawson, Lora

AU - Benatar, Michael G

AU - Usher, Sharon

AU - Sharma, Khema R

AU - Gautam, Shiva

AU - Narayanaswami, Pushpa

AU - Raynor, Elizabeth M.

AU - Watson, Mary Lou

AU - Shefner, Jeremy M.

PY - 2012/9/1

Y1 - 2012/9/1

N2 - 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.

AB - 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.

KW - Amyotrophic lateral sclerosis

KW - Clinical trials

KW - Electrical impedance myography

UR - http://www.scopus.com/inward/record.url?scp=84865342841&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84865342841&partnerID=8YFLogxK

U2 - 10.3109/17482968.2012.688837

DO - 10.3109/17482968.2012.688837

M3 - Article

C2 - 22670883

AN - SCOPUS:84865342841

VL - 13

SP - 439

EP - 445

JO - Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration

JF - Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration

SN - 2167-8421

IS - 5

ER -