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The primary endpoint was change in resting motor threshold (RMT).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>RMT was unchanged with 4 wk of mexiletine (combined active therapies) as compared to placebo, which showed a significant increase (<jats:italic>P<\/jats:italic> = .039). Reductions of motor evoked potential (MEP) amplitude (<jats:italic>P<\/jats:italic> = .013) and accommodation half\u2010time (<jats:italic>P<\/jats:italic> = .002), secondary outcome measures of cortical and axonal excitability, respectively, were also evident at 4 wk on mexiletine.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The relative stabilization of RMT in the treated subjects was unexpected and could be attributed to unaccounted sources of error or chance. However, a possible alternative cause is neuromodulation preventing an increase. The change in MEP amplitude and accommodation half\u2010time supports the reduction of cortical and axonal hyperexcitability with mexiletine.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mus.27146","type":"journal-article","created":{"date-parts":[[2020,12,19]],"date-time":"2020-12-19T12:30:54Z","timestamp":1608381054000},"page":"371-383","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Effects of mexiletine on hyperexcitability in sporadic amyotrophic lateral sclerosis: Preliminary findings from a small phase <scp>II<\/scp> randomized controlled trial"],"prefix":"10.1002","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4064-1032","authenticated-orcid":false,"given":"Michael D.","family":"Weiss","sequence":"first","affiliation":[{"name":"Department of Neurology University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric 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