{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T22:45:36Z","timestamp":1788561936840,"version":"build-2803163510"},"reference-count":39,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T00:00:00Z","timestamp":1768780800000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012355","name":"United European Gastroenterology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012355","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Chronic intestinal pseudo\u2010obstruction (CIPO) is a rare, severe disorder of gastrointestinal motility. Although 5\u2010hydroxytryptamine type 4 (5\u2010HT\n                      <jats:sub>4<\/jats:sub>\n                      ) receptor agonists stimulate gastrointestinal motility, few trials have assessed their therapeutic effects in patients with CIPO.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>\n                      To assess the efficacy and safety of velusetrag, a highly selective 5\u2010HT\n                      <jats:sub>4<\/jats:sub>\n                      receptor agonist,\u00a0in patients with CIPO.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This was a phase 2, placebo\u2010controlled, crossover, multiple (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091), multicenter, double\u2010blind, proof\u2010of\u2010concept trial. Eligible patients were aged 18\u201380\u2009years, had CIPO (idiopathic or secondary to neurodegenerative disorders) and received \u2265\u200930% of their daily caloric intake orally. Over four periods, each of four\u2009weeks, patients were randomly assigned to once\u2010daily, oral velusetrag 15\u2009mg (two periods) or placebo (two periods), with a 2\u2010week washout between each treatment period. The primary endpoint was the improvement in the weekly global gastrointestinal symptoms average index score (WGGSAIS) from the start to the end of each treatment period, assessed among patients who were responders or naive to previous 5\u2010HT\n                      <jats:sub>4<\/jats:sub>\n                      receptor agonist treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Overall, 17 patients with idiopathic CIPO received treatment and were included in safety analyses; efficacy was assessed in 15 patients. Mean (standard deviation) changes in WGGSAIS during treatment were \u22120.42 (0.693) for velusetrag and \u22120.19 (0.688) for placebo (between\u2010treatment difference: \u22120.24; 95% confidence interval: \u22120.553, 0.074;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.1279). No deaths or serious or treatment\u2010related treatment\u2010emergent adverse events were reported.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Velusetrag treatment was associated with improved symptoms versus placebo, although differences were not statistically significant at this sample size. Velusetrag was generally well tolerated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>ClinicalTrials.gov identifier: NCT05724069; EudraCT number: 2021\u2010000854\u201024<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nmo.70246","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T14:46:02Z","timestamp":1768833962000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Clinical Trial: Efficacy and Safety of Velusetrag in Chronic Intestinal Pseudo\u2010Obstruction: A Randomized, Phase 2, Placebo\u2010Controlled, Crossover, Multiple (\n                    <i>n<\/i>\n                    \u2009=\u20091), Proof\u2010of\u2010Concept Study"],"prefix":"10.1111","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7097-1492","authenticated-orcid":false,"given":"Carolina","family":"Malagelada","sequence":"first","affiliation":[{"name":"Digestive System Research Unit Vall d'Hebron University Hospital  Barcelona Spain"},{"name":"Network Biomedical Research Center for Liver and Digestive Diseases (CIBEREHD)  Madrid Spain"},{"name":"Autonomous University of Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0867-5873","authenticated-orcid":false,"given":"Roberto","family":"De Giorgio","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine University of Ferrara  Ferrara Italy"},{"name":"Internal Medicine Unit St. Annunziata Hospital  Cento Ferrara Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1258-0569","authenticated-orcid":false,"given":"Rosanna Francesca","family":"Cogliandro","sequence":"additional","affiliation":[{"name":"Internal Medicine and Digestive Pathophysiology Sant'Orsola\u2010Malpighi University Hospital  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3247-1539","authenticated-orcid":false,"given":"Luis","family":"Alcal\u00e1\u2010Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Digestive System Research Unit Vall d'Hebron University Hospital  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8644-1135","authenticated-orcid":false,"given":"Anna","family":"Costanzini","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine University of Ferrara  Ferrara Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Scuderi","sequence":"additional","affiliation":[{"name":"R&amp;D Department Alfasigma S.p.A.  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