{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,22]],"date-time":"2026-03-22T00:44:41Z","timestamp":1774140281331,"version":"3.50.1"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,10,11]],"date-time":"2019-10-11T00:00:00Z","timestamp":1570752000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,10,11]],"date-time":"2019-10-11T00:00:00Z","timestamp":1570752000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["NNF17OC0029426"],"award-info":[{"award-number":["NNF17OC0029426"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Trials"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n              <jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Neuropathic pain is a common pain condition that has a major negative impact on health-related quality of life. However, despite decades of research, it remains difficult to treat neuropathic pain. Lacosamide is a sodium-channel blocker that is efficacious in animal models of neuropathic pain. In humans, its effect in neuropathic pain is inconclusive, based on inconsistent results and very large placebo responses. Previous trials have not used patient stratification or looked for predictors for response.<\/jats:p>\n              <\/jats:sec>\n              <jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>This study will be conducted as a multicenter, randomized, double-blind, placebo-controlled, parallel, phase 2, proof-of-concept, phenotype-stratified study. The study will enroll 108 patients with peripheral neuropathic pain who will be randomized to a 12-week treatment with lacosamide or placebo up to 400\u2009mg\/day in a 2:1 ratio. The primary objective is to compare the change in the mean value of the patients\u2019 daily ratings of average pain intensity from baseline to the last week of treatment in patients with and without the irritable nociceptor phenotype in the per-protocol population. A supportive objective is to compare the effect of lacosamide with that of placebo in the two phenotypes. Secondary and tertiary outcomes include the Patient Global Impression of Change, pain relief, presence of 30% and 50% pain reduction, sleep disturbance, depression, and anxiety.<\/jats:p>\n              <\/jats:sec>\n              <jats:sec>\n                <jats:title>Discussion<\/jats:title>\n                <jats:p>We will examine the concept of individualized therapy based on phenotyping, and expect that this study will provide important information on the usefulness of lacosamide in the treatment of peripheral neuropathic pain.<\/jats:p>\n              <\/jats:sec>\n              <jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p>ClinicalTrials.gov, <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/results?cond=&amp;term=NCT03777956&amp;cntry=&amp;state=&amp;city=&amp;dist=\">NCT03777956<\/jats:ext-link>. Registered on 18 December 2018.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13063-019-3695-7","type":"journal-article","created":{"date-parts":[[2019,10,11]],"date-time":"2019-10-11T07:11:42Z","timestamp":1570777902000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Effect of lacosamide in peripheral neuropathic pain: study protocol for a randomized, placebo-controlled, phenotype-stratified trial"],"prefix":"10.1186","volume":"20","author":[{"given":"Malin E.","family":"Carmland","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa","family":"Kreutzfeldt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jakob V.","family":"Holbech","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niels T.","family":"Andersen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Troels S.","family":"Jensen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flemming W.","family":"Bach","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S\u00f8ren H.","family":"Sindrup","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5541-0240","authenticated-orcid":false,"given":"Nanna B.","family":"Finnerup","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,10,11]]},"reference":[{"key":"3695_CR1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.2","volume":"3","author":"L Colloca","year":"2017","unstructured":"Colloca L, Ludman T, Bouhassira D, Baron R, Dickenson AH, Yarnitsky D, et al. 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The study is approved by the Ethical Committee of the Central Denmark Region, which includes approval also for the Region of Southern Denmark, and thus there is local ethical approval for all participating centers (no. 1-10-72-264-18), the Danish Medicines Agency (no. 201881482), and the Data Protection Agency (via the Central Denmark region\u2019s internal notification) (no. 2016-015000001). The study is registered with the EU Clinical Trials Register (Eudra CT 2018-003110-40) and  (NCT03777956). Important protocol modifications will be communicated to all relevant parties mentioned above. Informed consent will be obtained from all participants from the investigators and we will follow the ICH Good Clinical Practice (GCP) guidelines, and the project will be monitored by the GCP units at Aarhus and Odense University Hospitals, for both planned and unplanned visits, according to a specific plan stated by the local GCP units. All methods used in the study are clinically established, and the project manager\/staff have extensive clinical experience in using them.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"MEC, JVH, SHS, and NTA declare no competing interests. NBF has received honoraria for serving on advisory boards or speaker panels from Teva, Novartis, Astellas, Gr\u00fcnenthal, Mitshubishe Tanabe, Merck, and Novartis. TSJ has received honoraria for serving on advisory boards from Pfizer, Gr\u00fcnenthal, and Aptinyx. FWB has received honoraria for serving on advisory boards from Novartis and TEVA.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"588"}}