{
  "abstract": "Introduction Metabolic dysfunction-associated steatohepatitis (MASH), formerly known as non-alcoholic steatohepatitis (NASH), is the hepatic manifestation of the metabolic syndrome. When it co-occurs with type 2 diabetes (T2DM), it presents a significant therapeutic challenge due to a higher risk of fibrosis progression and adverse outcomes. While new treatments for MASH are emerging, their efficacy in the T2DM subpopulation remains an unmet need. Chiglitazar is a novel peroxisome proliferator-activated receptor pan-agonist that regulates key pathways in lipid metabolism, glucose homeostasis and inflammation. This trial aims to evaluate the efficacy and safety of chiglitazar as a combination therapy for patients with MASH and T2DM.Methods and analysis This is a prospective, multicentre, randomised, double-blind, placebo-controlled study. This trial will enrol 300 adult patients aged 18–75 years with biopsy-confirmed MASH and fibrosis stage F1 or higher. Participants will be randomised (1:1) to receive either chiglitazar 48 mg daily or a matching placebo. All participants will also receive background therapy consisting of vitamin E (100 mg three times a day) and polyene phosphatidyl choline (456 mg three times a day). The treatment duration is 78 weeks. The primary efficacy endpoint is resolution of steatohepatitis with no worsening of liver fibrosis. Key secondary endpoints include improvement in liver fibrosis by at least one stage and changes in metabolic and liver safety biomarkers.Ethics and dissemination Ethical approval has been obtained from the Shanghai Punan Hospital of Pudong New District Ethics Committee (Punan Branch of Renji Hospital Ethics Committee, Shanghai Jiaotong University School of Medicine). KY2025-066. The findings will be disseminated through publication in peer-reviewed journals and presentations at scientific conferences.Trial registration number NCT07303803.",
  "authors": [
    {
      "affiliations": [
        "Department of Gastroenterology, Ren Ji Hospital, Punan Campus, School of Medicine, Shanghai Jiao Tong University, Shanghai, China",
        "Department of Gastroenterology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China",
        "Shanghai Institute of Digestive Disease, Key Laboratory of Gastroenterology and Hepatology, Chinese Ministry of Health (Shanghai Jiao Tong University), Shanghai, China"
      ],
      "name": "Kai He"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Ren Ji Hospital, Punan Campus, School of Medicine, Shanghai Jiao Tong University, Shanghai, China"
      ],
      "name": "Fengyuan Chen"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Ren Ji Hospital, Punan Campus, School of Medicine, Shanghai Jiao Tong University, Shanghai, China"
      ],
      "name": "Rong Shao"
    },
    {
      "affiliations": [
        "Department of Ultrasound, Ren Ji Hospital, Punan Campus, School of Medicine, Shanghai Jiao Tong University, Shanghai, China"
      ],
      "name": "Wanjun Jiang"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China",
        "Shanghai Institute of Digestive Disease, Key Laboratory of Gastroenterology and Hepatology, Chinese Ministry of Health (Shanghai Jiao Tong University), Shanghai, China"
      ],
      "name": "Wenyi Gu"
    },
    {
      "affiliations": [
        "Department of Endocrinology and Metabolism, Ren Ji Hospital, Punan Campus, School of Medicine, Shanghai Jiao Tong University, Shanghai, China"
      ],
      "name": "Zeyu Huang"
    },
    {
      "affiliations": [
        "Department of Endocrinology and Metabolism, Ren Ji Hospital, Punan Campus, School of Medicine, Shanghai Jiao Tong University, Shanghai, China"
      ],
      "name": "Yunxia Gan"
    },
    {
      "affiliations": [
        "Department of Endocrinology and Metabolism, Ren Ji Hospital, Punan Campus, School of Medicine, Shanghai Jiao Tong University, Shanghai, China"
      ],
      "name": "Yan Wang"
    },
    {
      "affiliations": [
        "Department of Endocrinology and Metabolism, Ren Ji Hospital, Punan Campus, School of Medicine, Shanghai Jiao Tong University, Shanghai, China"
      ],
      "name": "Hong Wu"
    },
    {
      "affiliations": [
        "Department of Ultrasound, Ren Ji Hospital, Punan Campus, School of Medicine, Shanghai Jiao Tong University, Shanghai, China"
      ],
      "name": "Yunxin Zhao"
    },
    {
      "affiliations": [
        "Department of Ultrasound, Ren Ji Hospital, Punan Campus, School of Medicine, Shanghai Jiao Tong University, Shanghai, China"
      ],
      "name": "Bei Zhang"
    },
    {
      "affiliations": [
        "Clinical Research Institute, Institute of Advanced Clinical Medicine, Peking University, Beijing, China"
      ],
      "name": "Lingling Gao"
    },
    {
      "affiliations": [
        "Clinical Research Institute, Institute of Advanced Clinical Medicine, Peking University, Beijing, China"
      ],
      "name": "Xiaoyan Yan"
    },
    {
      "affiliations": [
        "Clinical Research Institute, Institute of Advanced Clinical Medicine, Peking University, Beijing, China"
      ],
      "name": "Chen Yao"
    },
    {
      "affiliations": [
        "Shenzhen Chipscreen Biosciences Co., Ltd, Shenzhen, Guangdong, China"
      ],
      "name": "Chaoyun Shen"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China",
        "Shanghai Institute of Digestive Disease, Key Laboratory of Gastroenterology and Hepatology, Chinese Ministry of Health (Shanghai Jiao Tong University), Shanghai, China"
      ],
      "name": "Peixuan Ji"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China",
        "Shanghai Institute of Digestive Disease, Key Laboratory of Gastroenterology and Hepatology, Chinese Ministry of Health (Shanghai Jiao Tong University), Shanghai, China"
      ],
      "name": "Jianyi Wei"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China",
        "Shanghai Institute of Digestive Disease, Key Laboratory of Gastroenterology and Hepatology, Chinese Ministry of Health (Shanghai Jiao Tong University), Shanghai, China"
      ],
      "name": "Yuexiang Bian"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China",
        "Shanghai Institute of Digestive Disease, Key Laboratory of Gastroenterology and Hepatology, Chinese Ministry of Health (Shanghai Jiao Tong University), Shanghai, China"
      ],
      "name": "Yawen Lu"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China",
        "Shanghai Institute of Digestive Disease, Key Laboratory of Gastroenterology and Hepatology, Chinese Ministry of Health (Shanghai Jiao Tong University), Shanghai, China"
      ],
      "name": "Adila Abuduaini"
    },
    {
      "affiliations": [
        "Department of Endocrinology and Metabolism, Ren Ji Hospital, Punan Campus, School of Medicine, Shanghai Jiao Tong University, Shanghai, China"
      ],
      "name": "Lianyong Liu"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Ren Ji Hospital, Punan Campus, School of Medicine, Shanghai Jiao Tong University, Shanghai, China",
        "Department of Gastroenterology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China",
        "Shanghai Institute of Digestive Disease, Key Laboratory of Gastroenterology and Hepatology, Chinese Ministry of Health (Shanghai Jiao Tong University), Shanghai, China"
      ],
      "name": "Hai Li"
    }
  ],
  "title": "Chiglitazar in combination with anti-inflammatory and hepatoprotective therapy for the treatment of MASH associated with T2DM: a prospective, multicentre, randomised, double-blind, placebo-controlled study protocol",
  "uid": "9110c13f-38a7-54b9-bc31-e51cb76acabc"
}