Effectiveness and safety analysis of Danggui Shaoyao Powder for the treatment of non-alcoholic fatty liver disease: study protocol for a randomized, double-blind, placebo-controlled clinical trial

Huang et al. BMC Complementary Medicine and Therapies https://doi.org/10.1186/s12906-023-03948-3 (2023) 23:126 BMC Complementary Medicine and Therapies Open Access STUDY PROTOCOL Effectiveness and safety analysis of Danggui Shaoyao Powder for the treatment of non‑alcoholic fatty liver disease: study protocol for a randomized, double‑blind, placebo‑controlled clinical trial Qian Huang1,2,3†, Ziming An1,2,3†, Xin Xin3, Qinmei Sun1, Siting Gao1, Sheng Lv1, Xiao Xu1, Shuohui Yang4, Fang Lu5, Jie Yuan5, Yu Zhao1, Yiyang Hu1,2,3, Ping Liu1,2,3 and Qin Feng1,2,3* Abstract Background The incidence of non-alcoholic fatty liver disease (NAFLD) has been on the rise in recent years, and there are no effective drugs to treat NAFLD; therefore, effective prevention and treatment of NAFLD have become a new challenge. Danggui Shaoyao Powder (DGSY) is a classic prescription commonly used in clinical practice and has been shown to reduce hepatic steatosis in patients with NAFLD. In addition, previous studies have shown that DGSY can alleviate hepatic steatosis and inflammation in NAFLD mice. Although clinical practice and basic studies have shown that DGSY is effective in NAFLD, high levels of clinical evidence are lacking. Therefore, a standardized RCT study protocol is required to evaluate its clinical efficacy and safety. Methods and analysis This study will be a randomized, double-blind, placebo-controlled, and single-center trial. According to the random number table, NAFLD participants will be randomly divided into the DGSY or placebo group for 24 weeks. The follow-up period will be 6 weeks after drug withdrawal. The primary outcome is the relative change in MRI-proton density fat fraction (MRI-PDFF) from baseline to 24 weeks. Absolute changes in serum alanine aminotransferase (ALT), liver stiffness measurement (LSM), body mass index (BMI), blood lipid, blood glucose, and insulin resistance index will be selected as secondary outcomes to comprehensively evaluate the clinical efficacy of DGSY in the treatment of NAFLD. The safety of DGSY will be evaluated by renal function, routine blood and urine tests, and electrocardiogram. Discussion This study will provide evidence-based medical corroboration for the clinical application of DGSY and promote the development and application of this classic prescription. Trial registration http://www.chictr.org.cn. Trial number: ChiCTR2000029144. Registered on 15 Jan 2020. Keywords Danggui Shaoyao Powder, Non-alcoholic fatty liver disease, Randomized controlled trial, Traditional Chinese medicine † Qian Huang and Ziming An are equally contributed to this work. *Correspondence: Qin Feng Full list of author information is available at the end of the article © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativeco mmons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Huang et al. BMC Complementary Medicine and Therapies (2023) 23:126 Introduction Liver steatosis > 5% is defined as Non-alcoholic fatty liver disease (NAFLD) [1]. The disease spectrum includes non-alcoholic fatty liver (NAFL), non-alcoholic steatohepatitis (NASH), and related liver fibrosis and cirrhosis [2, 3]. NAFLD can not only cause endstage liver disease and death but is also closely associated with a higher incidence of metabolic syndrome (MetS), type 2 diabetes mellitus (T2DM), arteriosclerotic cardiovascular disease, and colorectal tumors [4]. According to epidemiological statistics and analysis, the prevalence rate of NAFLD among adults in the world is as high as 25%, and that in Western countries is about 17%-46% NASH has become the leading cause of hepatocellular carcinoma in the United States and most common reason for liver transplantation [5, 6]. Therefore, active prevention and control of NAFLD are of great social significance. The etiology of NAFLD is complex, and its exact pathogenesis has not been fully elucidated. Currently, no drug has been approved by the Food and Drug Administration to treat NAFLD. “Control your mouth, take your legs” is an important therapeutic measure to prevent and treat NAFLD, but patients often have difficulty controlling their diet and maintaining their ideal weight. In addition, obeticholic acid, which has completed Phase III trials as a farnesoid X receptor (FXR) agonist that improves insulin sensitivity and reduces hepatic steatosis, inflammation, and fibrosis, showed promising results in NASH; however, pruritus was present in 23% of treated patients, and low-density lipoprotein cholesterol (LDL-C) was rapidly elevated in some patients. Therefore, drug safety requires long-term evaluation [7]. Given the high incidence of NAFLD and the lack of specific therapeutic drugs, the research and development of new drugs for NAFLD is particularly important. Traditional Chinese medicine (TCM) has been widely used in China. As a drug treatment approach for NAFLD, TCM is effective in promoting the reversal of NAFLD and improving clinical symptoms and laboratory indicators and is likely to provide a comprehensive therapeutic advantage in the treatment of NAFLD. Danggui Shaoyao Powder (DGSY, composed of Danggui, Shaoyao, Fuling, Baizhu, Zexie, and Chuanxiong) was obtained from the Synopsis Golden Chamber. Previous study by other researchs found that DGSY could decrease ALT and improve hepatic fat deposition assessed by elastography in NAFLD patients [8]. Animal studies also revealed that it could alleviate hepatic fat deposition and inflammation in NAFLD mice [9]. However, the current relevant clinical trial evidence levels are insufficient. Therefore, this study will systematically evaluate the clinical efficacy and safety of DGSY in treating NAFLD Page 2 of 8 through a prospective design and a randomized, doubleblind, placebo-controlled, single-center trial. Methods Study design overview This is a randomized, double-blind, placebo-controlled, and single-center trial protocol. This clinical trial was registered at Chictr.org.cn (ChiCTR2000029144). A brief flowchart of the study flo (...truncated)