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Acute Effects of Riluzole and Retigabine on Axonal Excitability in Patients With Amyotrophic Lateral Sclerosis: A Randomized, Double‐Blind, Placebo‐Controlled, Crossover Trial
Author(s) -
Kovalchuk Maria O.,
Heuberger Jules A.A.C.,
Sleutjes Boudewijn T.H.M.,
Ziagkos Dimitrios,
van den Berg Leonard H.,
Ferguson Toby A.,
Franssen Hessel,
Groeneveld Geert Jan
Publication year - 2018
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.1096
Subject(s) - riluzole , amyotrophic lateral sclerosis , placebo , medicine , crossover study , anesthesia , disease , pathology , alternative medicine
Increased excitability of motor neurons in patients with amyotrophic lateral sclerosis (ALS) may be a relevant factor leading to motor neuron damage. This randomized, double‐blind, three‐way crossover, placebo‐controlled study evaluated peripheral motor nerve excitability testing as a biomarker of hyperexcitability and assessed the effects of riluzole and retigabine in 18 patients with ALS. We performed excitability testing at baseline, and twice after participants had received a single dose of either 100 mg riluzole, 300 mg retigabine, or placebo. Between‐ and within‐day repeatability was at least acceptable for 14 out of 18 recorded excitability variables. No effects of riluzole on excitability testing were observed, but retigabine significantly decreased strength‐duration time‐constant (9.2%) and refractoriness at 2 ms (10.2) compared to placebo. Excitability testing was shown to be a reliable biomarker in patients with ALS, and the acute reversal of previously abnormal variables by retigabine justifies long‐term studies evaluating the impact on disease progression and survival.