{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T17:41:43Z","timestamp":1781113303093,"version":"3.54.1"},"reference-count":19,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T00:00:00Z","timestamp":1677628800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000038","name":"U.S. Food and Drug Administration","doi-asserted-by":"publisher","award":["1R01FD006349"],"award-info":[{"award-number":["1R01FD006349"]}],"id":[{"id":"10.13039\/100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National institutes of Health","doi-asserted-by":"crossref","award":["2T32DK007754-22"],"award-info":[{"award-number":["2T32DK007754-22"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National institutes of health","doi-asserted-by":"crossref","award":["5T32HL007734"],"award-info":[{"award-number":["5T32HL007734"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National institutes of health","doi-asserted-by":"crossref","award":["5T32HL007734"],"award-info":[{"award-number":["5T32HL007734"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Richard and Sandra Cummings Research Fellowship of the Beth Israel Deaconess Medical Center Department of Surgery"},{"name":"The Boston Children\u2019s Vascular Biology Program"},{"name":"The Boston Children\u2019s Hospital Surgical Foundation"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Short bowel syndrome (SBS) is a leading cause of intestinal failure resulting in parenteral nutrition (PN) dependence and nutritional deficiencies. Long-term PN use is associated with the development of sepsis and intestinal failure-associated liver disease. Achieving enteral autonomy is the optimal way to prevent these complications. In SBS, the decreased intestinal length, bile acid deficiency, and rapid transit time contribute to fat malabsorption and continued PN dependence. We propose the use of an immobilized lipase cartridge (ILC; RELiZORB) that connects in-line with enteral feed tubing sets and is designed to breakdown the majority of fats provided in enteral nutrition (EN). Preclinical studies have demonstrated both improved fat and fat-soluble vitamin absorption with ILC use in a porcine model of SBS. To evaluate the clinical applicability of these findings, we designed a phase 3, open labeled, single center, clinical trial to determine the safety, tolerability, and efficacy of the RELiZORB enzyme cartridge when used daily with EN for 90 days.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>The patient population will include PN dependent children with SBS, aged 2\u201318 years. The primary outcome is the change in PN calories from baseline, assessed weekly throughout the study. Changes in growth Z-scores, 72-hour fecal fat and coefficient of fat absorption, plasma fatty acids and fat-soluble vitamins will also be evaluated. Assessment of change in continuous outcomes will be made using the area under the curve, expressed as a percent change relative to baseline, calculated over study day 7 to 90 (AUC<jats:sub>7-90<\/jats:sub>). The incidence of adverse events will be monitored and summarized by system organ class.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Discussion<\/jats:title>\n<jats:p>If successful, RELiZORB may offer a safe alternative to reducing PN dependence and achieving enteral autonomy in pediatric intestinal failure. These results would be clinically significant given the clear association between long-term PN use and complications in SBS.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\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\/show\/NCT03530852\" xlink:type=\"simple\">NCT03530852<\/jats:ext-link>; registered on May 21<jats:sup>st<\/jats:sup>, 2018, last update posted on September 14<jats:sup>th<\/jats:sup>, 2022.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0282248","type":"journal-article","created":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T18:30:32Z","timestamp":1677695432000},"page":"e0282248","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["Fat digestion using RELiZORB in children with short bowel syndrome who are dependent on parenteral nutrition: Protocol for a 90-day, phase 3, open labeled study"],"prefix":"10.1371","volume":"18","author":[{"given":"Savas T.","family":"Tsikis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott C.","family":"Fligor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul D.","family":"Mitchell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas 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