Electrical impedance myography as a biomarker to assess ALS progression.
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.
Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA. srutkove@bidmc.harvard.edu
Seward B
SB
Rutkove
James B
JB
Caress
Michael S
MS
Cartwright
Ted M
TM
Burns
Judy
J
Warder
William S
WS
David
Namita
N
Goyal
Nicholas J
NJ
Maragakis
Lora
L
Clawson
Michael
M
Benatar
Sharon
S
Usher
Khema R
KR
Sharma
Shiva
S
Gautam
Pushpa
P
Narayanaswami
Elizabeth M
EM
Raynor
Mary Lou
ML
Watson
Jeremy M
JM
Shefner
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000401:mortality* / Q000503:physiopathology*; D002986:Clinical Trials as Topic; D018450:Disease Progression; D017097:Electric Impedance; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000503:physiopathology; D009213:Myography / Q000379:methods*; D015996:Survival Rate; D013997:Time Factors; D055815:Young Adult