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One of the underlying pathophysiological mechanisms is insulin resistance (IR). Traditional Chinese medicine (TCM) has showed potential benefits in the management of NAFLD. Lingguizhugan decoction (LGZG) is a representative Chinese herbal formula; however, there is still no rigorous clinical trial supporting its application.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods\/design<\/jats:title>\n                    <jats:p>This study will be a three-arm, dose-optimization, randomized, double-blinded, placebo-controlled clinical trial. A total of 243 patients with NAFLD will be recruited and randomly assigned to the standard dose LGZG (SLGD) group, low dose LGZG (LLGD) group, or the placebo group based on a ratio of 1:1:1. The treatment period will be 12\u2009weeks and the follow-up period will last 4\u2009weeks. The primary outcome will be the proportions of participants with at least a 1-unit decrease of HOMA-IR from baseline to 12\u2009weeks. Secondary outcomes will include the changes of body weight, body mass index, liver function, blood lipid metabolism, blood glucose metabolism, inflammatory responses, liver-kidney echo ratio by ultrasound, and various scales. Biological samples will also be collected for future researches on mechanism exploration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This study will provide initial evidence regarding the efficacy and safety of LGZG in the treatment of NAFLD with spleen-yang deficiency pattern and promote its application in community healthcare centers. In addition, potential mechanisms will be explored based on studies of oral and gut microbiota.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>\n                      Chinese Clinical Trial Registry,\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.chictr.org.cn\/edit.aspx?pid=24555&amp;htm=4\">ChiCTR1800014364<\/jats:ext-link>\n                      . Registered on 1 January 2018. The final protocol version was V3.0.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13063-020-04362-7","type":"journal-article","created":{"date-parts":[[2020,6,10]],"date-time":"2020-06-10T08:02:47Z","timestamp":1591776167000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Traditional Chinese medicine Lingguizhugan decoction treating non-alcoholic fatty liver disease with spleen-yang deficiency pattern: Study protocol for a multicenter randomized controlled trial"],"prefix":"10.1186","volume":"21","author":[{"given":"Jingjuan","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruirui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengfu","family":"You","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiyong","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guang","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baocheng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,6,10]]},"reference":[{"key":"4362_CR1","doi-asserted-by":"publisher","first-page":"i4428","DOI":"10.1136\/bmj.i4428","volume":"354","author":"J Glen","year":"2016","unstructured":"Glen J, Floros L, Day C, Pryke R. 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Before the implementation of the study, the study protocol was modified three times and approved by the ethics committee, respectively. The final protocol version was V3.0. We will guarantee that this study is conducted in the principles of the Declaration of Helsinki and the principles of the Quality Control of Clinical Trial of Drugs in China. All participants need to sign the informed consent before enrollment, and will be informed about the purpose, probable risks and benefits, arrangement, the rights and obligations, and can quit the study at any time. Signed informed consent from patient willing to participate in the trial will be collected by clinical investigators. The informed consent form will be available from the corresponding author on request.","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 no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"512"}}