{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T02:12:01Z","timestamp":1770343921116,"version":"3.49.0"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,2,12]],"date-time":"2021-02-12T00:00:00Z","timestamp":1613088000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,2,12]],"date-time":"2021-02-12T00:00:00Z","timestamp":1613088000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"crossref","award":["20K19311"],"award-info":[{"award-number":["20K19311"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Trials"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Liver cirrhosis is the irreversible fibrosis of the liver and causes refractory ascites and hepatic encephalopathy, which might not respond to treatment. Living donor liver transplantation (LDLT) is an effective treatment for patients with cirrhosis. However, post-LDLT patients are prone to muscle atrophy and sarcopenia. Therefore, physiotherapy of post-LDLT patients is essential for preventing the progression of sarcopenia. Recently, rehabilitation using neuromuscular electrical stimulation (NMES) has been reported to be useful for preventing the progression of sarcopenia. Similarly, nutrition therapy is essential for post-LDLT patients because these patients frequently experience malnutrition. However, the effects of combined NMES and nutrition therapy on post-LDLT patients remain unknown.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods\/design<\/jats:title>\n                <jats:p>This open-label, randomized, parallel-group study will compare the effects of combined therapy with NMES and branched-chain amino acids (BCAA) with those of NMES alone in patients with decompensated cirrhosis after LDLT. After LDLT, 50 patients with decompensated cirrhosis will be randomly assigned to receive NMES with BCAA or NMES without BCAA. The duration of the intervention will be 3\u2009months. To analyze the change in skeletal muscle mass, InBody 770 body composition and body water analysis and ultrasonography will be performed before LDLT and 4\u00a0weeks and 12\u00a0weeks post-LDLT. The primary endpoint is changes in the skeletal muscle mass from baseline to 3\u2009months. Important secondary endpoints are the changes in the skeletal muscle mass from baseline to 1\u2009month and changes in the quadriceps strength from baseline to 1\u2009month.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Discussion<\/jats:title>\n                <jats:p>The results of this study are expected to provide evidence regarding the effect of NMES combined with BCAA therapy on the skeletal muscle of post-LDLT patients.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p>Japan Registry of Clinical Research <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/jrct.niph.go.jp\/\">jRCTs071190051<\/jats:ext-link>. Registered on February 26, 2020.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13063-021-05086-y","type":"journal-article","created":{"date-parts":[[2021,2,12]],"date-time":"2021-02-12T20:30:21Z","timestamp":1613161821000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Comparative study of the effect of neuromuscular electrical stimulation and oral administration of branched-chain amino acid on preventing sarcopenia in patients after living-donor liver transplantation: study protocol for an open-label randomized controlled trial"],"prefix":"10.1186","volume":"22","author":[{"given":"Masafumi","family":"Haraguchi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kunihiro","family":"Ichinose","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8564-0490","authenticated-orcid":false,"given":"Hisamitsu","family":"Miyaaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masatoshi","family":"Hanada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masanori","family":"Fukushima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryu","family":"Sasaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Miuma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takanobu","family":"Hara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tota","family":"Kugiyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akihiko","family":"Soyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaaki","family":"Hidaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayumi","family":"Tsuji","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rintaro","family":"Yano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Motohiro","family":"Sekino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideaki","family":"Takahata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susumu","family":"Eguchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuhiko","family":"Nakao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,2,12]]},"reference":[{"issue":"8","key":"5086_CR1","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1056\/NEJMra1504367","volume":"375","author":"PS Ge","year":"2016","unstructured":"Ge PS, Runyon BA. Treatment of patients with cirrhosis. N Engl J Med. 2016;375(8):767\u201377.","journal-title":"N Engl J Med"},{"issue":"7","key":"5086_CR2","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1007\/s00535-016-1216-y","volume":"51","author":"H Fukui","year":"2016","unstructured":"Fukui H, Saito H, Ueno Y, Uto H, Obara K, Sakaida I, Shibuya A, Seike M, Nagoshi S, Segawa M, et al. Evidence-based clinical practice guidelines for liver cirrhosis 2015. J Gastroenterol. 2016;51(7):629\u201350.","journal-title":"J Gastroenterol"},{"issue":"4","key":"5086_CR3","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1007\/s12072-019-09963-2","volume":"13","author":"M Haraguchi","year":"2019","unstructured":"Haraguchi M, Miuma S, Masumoto H, Ichikawa T, Kanda Y, Sasaki R, Fukushima M, Miyaaki H, Taura N, Nakao K. Bacteroides in colonic mucosa-associated microbiota affects the development of minimal hepatic encephalopathy in patients with cirrhosis. Hepatol Int. 2019;13(4):482\u20139.","journal-title":"Hepatol Int"},{"issue":"1","key":"5086_CR4","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/j.nut.2014.07.005","volume":"31","author":"T Hanai","year":"2015","unstructured":"Hanai T, Shiraki M, Nishimura K, Ohnishi S, Imai K, Suetsugu A, Takai K, Shimizu M, Moriwaki H. Sarcopenia impairs prognosis of patients with liver cirrhosis. Nutrition (Burbank, Los Angeles County, Calif). 2015;31(1):193\u20139.","journal-title":"Nutrition (Burbank, Los Angeles County, Calif)"},{"issue":"12","key":"5086_CR5","doi-asserted-by":"publisher","first-page":"1416","DOI":"10.1097\/MEG.0000000000000986","volume":"29","author":"A Hiraoka","year":"2017","unstructured":"Hiraoka A, Michitaka K, Kiguchi D, Izumoto H, Ueki H, Kaneto M, Kitahata S, Aibiki T, Okudaira T, Tomida H, et al. Efficacy of branched-chain amino acid supplementation and walking exercise for preventing sarcopenia in patients with liver cirrhosis. Eur J Gastroenterol Hepatol. 2017;29(12):1416\u201323.","journal-title":"Eur J Gastroenterol Hepatol"},{"issue":"1","key":"5086_CR6","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1007\/s12072-016-9762-1","volume":"11","author":"M Haraguchi","year":"2017","unstructured":"Haraguchi M, Miyaaki H, Ichikawa T, Shibata H, Honda T, Ozawa E, Miuma S, Taura N, Takeshima F, Nakao K. Glucose fluctuations reduce quality of sleep and of life in patients with liver cirrhosis. Hepatol Int. 2017;11(1):125\u201331.","journal-title":"Hepatol Int"},{"issue":"6","key":"5086_CR7","doi-asserted-by":"publisher","first-page":"595","DOI":"10.3390\/nu9060595","volume":"9","author":"H Nishikawa","year":"2017","unstructured":"Nishikawa H, Enomoto H, Ishii A, Iwata Y, Miyamoto Y, Ishii N, Yuri Y, Hasegawa K, Nakano C, Nishimura T, et al. Comparison of prognostic impact between the child-pugh score and skeletal muscle mass for patients with liver cirrhosis. Nutrients. 2017;9(6):595.","journal-title":"Nutrients"},{"issue":"3","key":"5086_CR8","doi-asserted-by":"publisher","first-page":"61","DOI":"10.4254\/wjh.v3.i3.61","volume":"3","author":"P Feltracco","year":"2011","unstructured":"Feltracco P, Barbieri S, Galligioni H, Michieletto E, Carollo C, Ori C. Intensive care management of liver transplanted patients. World J Hepatol. 2011;3(3):61\u201371.","journal-title":"World J Hepatol"},{"issue":"5","key":"5086_CR9","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1097\/00002060-199110000-00003","volume":"70","author":"SM Tuel","year":"1991","unstructured":"Tuel SM, Meythaler JM, Cross LL. Inpatient comprehensive rehabilitation after liver transplantation. Am J Phys Med Rehabil. 1991;70(5):242\u20135.","journal-title":"Am J Phys Med Rehabil"},{"issue":"7","key":"5086_CR10","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1053\/jlts.2003.50148","volume":"9","author":"V Karam","year":"2003","unstructured":"Karam V, Castaing D, Danet C, Delvart V, Gasquet I, Adam R, Azoulay D, Samuel D, Bismuth H. Longitudinal prospective evaluation of quality of life in adult patients before and one year after liver transplantation. Liver Transpl. 2003;9(7):703\u201311.","journal-title":"Liver Transpl"},{"issue":"1","key":"5086_CR11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1399-0012.2004.00306.x","volume":"19","author":"JB Krasnoff","year":"2005","unstructured":"Krasnoff JB, Vintro AQ, Ascher NL, Bass NM, Dodd MJ, Painter PL. Objective measures of health-related quality of life over 24 months post-liver transplantation. Clin Transpl. 2005;19(1):1\u20139.","journal-title":"Clin Transpl"},{"issue":"3","key":"5086_CR12","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1002\/lt.20088","volume":"10","author":"SK Epstein","year":"2004","unstructured":"Epstein SK, Freeman RB, Khayat A, Unterborn JN, Pratt DS, Kaplan MM. Aerobic capacity is associated with 100-day outcome after hepatic transplantation. Liver Transpl. 2004;10(3):418\u201324.","journal-title":"Liver Transpl"},{"issue":"2","key":"5086_CR13","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1007\/s00421-010-1502-y","volume":"110","author":"NA Maffiuletti","year":"2010","unstructured":"Maffiuletti NA. Physiological and methodological considerations for the use of neuromuscular electrical stimulation. Eur J Appl Physiol. 2010;110(2):223\u201334.","journal-title":"Eur J Appl Physiol"},{"issue":"2","key":"5086_CR14","doi-asserted-by":"publisher","first-page":"219","DOI":"10.5935\/0103-507X.20180036","volume":"30","author":"A Sachetti","year":"2018","unstructured":"Sachetti A, Carpes MF, Dias AS, Sbruzzi G. Safety of neuromuscular electrical stimulation among critically ill patients: systematic review. Rev Bras Ter Intensiva. 2018;30(2):219\u201325.","journal-title":"Rev Bras Ter Intensiva"},{"key":"5086_CR15","doi-asserted-by":"publisher","unstructured":"Hanada M, Soyama A, Hidaka M, Nagura H, Oikawa M, Tsuji A, Kasawara KT, Mathur S, Reid WD, Takatsuki M, et al. Effects of quadriceps muscle neuromuscular electrical stimulation in living donor liver transplant recipients: phase-II single-blinded randomized controlled trial. Clin Rehabil. 2019. https:\/\/doi.org\/10.1177\/0269215518821718.","DOI":"10.1177\/0269215518821718"},{"issue":"4","key":"5086_CR16","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1007\/s00534-011-0459-5","volume":"19","author":"R Yoshida","year":"2012","unstructured":"Yoshida R, Yagi T, Sadamori H, Matsuda H, Shinoura S, Umeda Y, Sato D, Utsumi M, Nagasaka T, Okazaki N, et al. Branched-chain amino acid-enriched nutrients improve nutritional and metabolic abnormalities in the early post-transplant period after living donor liver transplantation. J Hepatobiliary Pancreat Sci. 2012;19(4):438\u201348.","journal-title":"J Hepatobiliary Pancreat Sci"},{"issue":"3","key":"5086_CR17","doi-asserted-by":"publisher","first-page":"E22","DOI":"10.1111\/hepr.12718","volume":"47","author":"S Koya","year":"2017","unstructured":"Koya S, Kawaguchi T, Hashida R, Goto E, Matsuse H, Saito H, Hirota K, Taira R, Matsushita Y, Imanaga M, et al. Effects of in-hospital exercise on liver function, physical ability, and muscle mass during treatment of hepatoma in patients with chronic liver disease. Hepatol Res. 2017;47(3):E22\u2013e34.","journal-title":"Hepatol Res"},{"key":"5086_CR18","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.clnesp.2017.08.005","volume":"22","author":"AC Meeks","year":"2017","unstructured":"Meeks AC, Madill J. Sarcopenia in liver transplantation: a review. Clin Nutr ESPEN. 2017;22:76\u201380.","journal-title":"Clin Nutr ESPEN"},{"issue":"6","key":"5086_CR19","doi-asserted-by":"publisher","first-page":"1549","DOI":"10.1111\/ajt.12221","volume":"13","author":"T Kaido","year":"2013","unstructured":"Kaido T, Ogawa K, Fujimoto Y, Ogura Y, Hata K, Ito T, Tomiyama K, Yagi S, Mori A, Uemoto S. Impact of sarcopenia on survival in patients undergoing living donor liver transplantation. Am J Transplant. 2013;13(6):1549\u201356.","journal-title":"Am J Transplant"},{"issue":"2","key":"5086_CR20","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1016\/j.bbrc.2003.07.016","volume":"313","author":"H Moriwaki","year":"2004","unstructured":"Moriwaki H, Miwa Y, Tajika M, Kato M, Fukushima H, Shiraki M. Branched-chain amino acids as a protein- and energy-source in liver cirrhosis. Biochem Biophys Res Commun. 2004;313(2):405\u20139.","journal-title":"Biochem Biophys Res Commun"},{"issue":"3","key":"5086_CR21","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1002\/hep.24412","volume":"54","author":"T Kawaguchi","year":"2011","unstructured":"Kawaguchi T, Izumi N, Charlton MR, Sata M. Branched-chain amino acids as pharmacological nutrients in chronic liver disease. Hepatology. 2011;54(3):1063\u201370.","journal-title":"Hepatology"},{"issue":"7","key":"5086_CR22","doi-asserted-by":"publisher","first-page":"1792","DOI":"10.1016\/S0016-5085(03)00323-8","volume":"124","author":"G Marchesini","year":"2003","unstructured":"Marchesini G, Bianchi G, Merli M, Amodio P, Panella C, Loguercio C, Rossi Fanelli F, Abbiati R. Nutritional supplementation with branched-chain amino acids in advanced cirrhosis: a double-blind, randomized trial. Gastroenterology. 2003;124(7):1792\u2013801.","journal-title":"Gastroenterology"},{"issue":"1","key":"5086_CR23","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1002\/hep.26370","volume":"58","author":"P Amodio","year":"2013","unstructured":"Amodio P, Bemeur C, Butterworth R, Cordoba J, Kato A, Montagnese S, Uribe M, Vilstrup H, Morgan MY. The nutritional management of hepatic encephalopathy in patients with cirrhosis: International Society for Hepatic Encephalopathy and Nitrogen Metabolism Consensus. Hepatology. 2013;58(1):325\u201336.","journal-title":"Hepatology"},{"issue":"11","key":"5086_CR24","doi-asserted-by":"publisher","first-page":"1664","DOI":"10.3390\/nu4111664","volume":"4","author":"RJ Manders","year":"2012","unstructured":"Manders RJ, Little JP, Forbes SC, Candow DG. Insulinotropic and muscle protein synthetic effects of branched-chain amino acids: potential therapy for type 2 diabetes and sarcopenia. Nutrients. 2012;4(11):1664\u201378.","journal-title":"Nutrients"},{"issue":"6","key":"5086_CR25","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1056\/NEJMoa1102662","volume":"365","author":"MP Casaer","year":"2011","unstructured":"Casaer MP, Mesotten D, Hermans G, Wouters PJ, Schetz M, Meyfroidt G, Van Cromphaut S, Ingels C, Meersseman P, Muller J, et al. Early versus late parenteral nutrition in critically ill adults. N Engl J Med. 2011;365(6):506\u201317.","journal-title":"N Engl J Med"},{"issue":"5","key":"5086_CR26","doi-asserted-by":"publisher","first-page":"e001891","DOI":"10.1136\/bmjopen-2012-001891","volume":"2","author":"SM Parry","year":"2012","unstructured":"Parry SM, Berney S, Koopman R, Bryant A, El-Ansary D, Puthucheary Z, Hart N, Warrillow S, Denehy L. Early rehabilitation in critical care (eRiCC): functional electrical stimulation with cycling protocol for a randomised controlled trial. BMJ Open. 2012;2(5):e001891.","journal-title":"BMJ Open"}],"container-title":["Trials"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-021-05086-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s13063-021-05086-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-021-05086-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,12]],"date-time":"2021-02-12T20:49:36Z","timestamp":1613162976000},"score":1,"resource":{"primary":{"URL":"https:\/\/trialsjournal.biomedcentral.com\/articles\/10.1186\/s13063-021-05086-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,12]]},"references-count":26,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["5086"],"URL":"https:\/\/doi.org\/10.1186\/s13063-021-05086-y","relation":{},"ISSN":["1745-6215"],"issn-type":[{"value":"1745-6215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,12]]},"assertion":[{"value":"21 June 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 January 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 February 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The certified review board of Japan\u2019s Ministry of Health, Labor, and Welfare approved this protocol (no. CRB19-0015). Informed consent will be obtained from all study participants.","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":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"137"}}