{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T01:50:32Z","timestamp":1790905832263,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2018,4,18]],"date-time":"2018-04-18T00:00:00Z","timestamp":1524009600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"French Ministry of Health","award":["13-017"],"award-info":[{"award-number":["13-017"]}]},{"name":"APICIL Foundation"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pain"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>T\u2010type calcium channels have been shown to play an important role in the initiation and maintenance of neuropathic pain and represent a promising therapeutic target for new analgesic treatments. Ethosuximide (<jats:styled-content style=\"fixed-case\">ETX<\/jats:styled-content>), an anticonvulsant and a T\u2010type channel blocker has shown analgesic effect in several chronic pain models but has not yet been evaluated in patients with neuropathic pain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This proof\u2010of\u2010concept, multicentre, double\u2010blind, controlled and randomized trial compared the efficacy and safety of <jats:styled-content style=\"fixed-case\">ETX<\/jats:styled-content> (given as add\u2010on therapy) to an inactive control (<jats:styled-content style=\"fixed-case\">IC<\/jats:styled-content>) in 114 patients with non\u2010diabetic peripheral neuropathic pain. After a 7\u2010day run\u2010in period, eligible patients aged over 18\u00a0years were randomly assigned (1:1) to <jats:styled-content style=\"fixed-case\">ETX<\/jats:styled-content> or <jats:styled-content style=\"fixed-case\">IC<\/jats:styled-content> for 6\u00a0weeks. The primary outcome was the difference between groups in the pain intensity (% of change from the baseline to end of treatment) assessed in the intention\u2010to\u2010treat population. This study is registered with Eudra<jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content> (2013\u2010004801\u201026) and ClinicalTrials.gov (<jats:styled-content style=\"fixed-case\">NCT<\/jats:styled-content>02100046).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The study was stopped during the interim analysis due to the high number of adverse events in the active treatment group. <jats:styled-content style=\"fixed-case\">ETX<\/jats:styled-content> failed to reduce total pain and showed a poor tolerance in comparison to <jats:styled-content style=\"fixed-case\">IC<\/jats:styled-content>. In the <jats:italic>per\u2010protocol<\/jats:italic> analysis, <jats:styled-content style=\"fixed-case\">ETX<\/jats:styled-content> significantly reduced pain intensity by 15.6% (95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> \u221225.8; \u22125.4) from baseline compared to <jats:styled-content style=\"fixed-case\">IC<\/jats:styled-content> (\u22127.8%, 95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> \u221214.3; \u22121.3; <jats:italic>p\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0.033), but this result must be interpreted with caution because of a small subgroup of patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Ethosuximide did not reduce the severity of neuropathic pain and induces, at the doses used, many adverse events.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>This article shows that <jats:styled-content style=\"fixed-case\">ETX<\/jats:styled-content> is not effective to treat neuropathic pain. Nevertheless, <jats:italic>per\u2010protocol<\/jats:italic> analysis suggests a possible analgesic effect of <jats:styled-content style=\"fixed-case\">ETX<\/jats:styled-content>. Thus, our work adds significant knowledge to preclinical and clinical data on the benefits of T\u2010type calcium channel inhibition for the treatment of neuropathic pain.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ejp.1221","type":"journal-article","created":{"date-parts":[[2018,3,26]],"date-time":"2018-03-26T01:23:05Z","timestamp":1522027385000},"page":"1321-1330","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Efficacy and safety of a T\u2010type calcium channel blocker in patients with neuropathic pain: A proof\u2010of\u2010concept, randomized, double\u2010blind and controlled trial"],"prefix":"10.1002","volume":"22","author":[{"given":"N.","family":"Kerckhove","sequence":"first","affiliation":[{"name":"Service de Pharmacologie M\u00e9dicale Direction de la Recherche Clinique et de l'Innovation CETD, CIC, CNRS, SIGMA Clermont, ICCF, Service de Pharmacie Universit\u00e9 Clermont Auvergne CHU Clermont\u2010Ferrand, 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