💬In plain words
What the trial is, and whether it could suit you
The purpose of this study is to evaluate the efficacy and safety of a short-term (12-week) prehabilitation strategy combining mazdutide (a novel GLP-1/GCG receptor dual agonist) with lifestyle optimization, compared to lifestyle optimization alone, in potential living liver transplantation donors with metabolic dysfunction-associated steatohepatitis (MASLD).
Overweight or obese individuals who intend to donate a portion of their liver but are temporarily disqualified due to hepatic steatosis will be recruited across multiple clinical centers. Participants will be randomly assigned in a 1:1 ratio to either the experimental group (mazdutide subcutaneous injection once weekly plus standardized lifestyle counseling) or the control group (placebo subcutaneous injection once weekly plus standardized lifestyle counseling).
The primary objective is to determine whether the short-term addition
Sign in to get the eligibility rules as simple questions to take to your doctor.
📋 Eligibility rules (as published)
Inclusion Criteria:
* Age between 18 and 60 years old at the time of signing the informed consent form.
* Overweight, defined as Body Mass Index (BMI) ≥ 24 kg/m².
* Diagnosed with MASLD by non-invasive means (conventional ultrasound, FibroScan®, or MRI), with a Controlled Attenuation Parameter (CAP) ≥ 268 dB/m via FibroScan®.
* Histologically confirmed MASLD without any liver fibrosis, presenting a NAS ≥ 3, including a steatosis subscore ≥ 2 (subscores for hepatocyte ballooning and lobular inflammation are not limited).
* Meets ethical and legal regulations, voluntarily donates a portion of the liver, and the corresponding potential liver transplant recipient must be a spouse or a direct or collateral blood relative within three generations.
* Understands all procedures and follow-up requirements of the study, participates voluntarily, and signs the written informed consent form in person.
Exclusion Criteria:
* Liver biopsy indicates complication with any degree of liver fibrosis.
* Failure to diagnose overweight or MASLD by non-invasive means, including BMI \< 24 kg/m² and/or CAP \< 268 dB/m.
* Histological evaluation shows a total NAS \< 3 and/or a steatosis subscore \< 2.
* Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) \> 5 × upper limit of normal (ULN) at screening, and/or ALT or AST levels increase by more than 1 fold compared to baseline during screening, which is considered clinically significant by the investigator.
* Total bilirubin (TBil) \> 25.6 μmol/L (1.5 mg/dL), and/or alkaline phosphatase (ALP) \> 2 × ULN, and/or International Normalized Ratio (INR) \> 1.35 at screening.
* Platelet count \< 150,000/μL at screening, unless considered by the investigator to reflect the patient's daily baseline level and portal hypertension is absent.
* Estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73m² based on the CKD-EPI formula at screening.
* Glycated hemoglobin (HbA1c) \> 9.5% at screening.
* Unstable weight, defined as self-reported weight change \> 5% within 90 days prior to screening up to the time of screening.
* Presence of other clearly defined etiologies causing chronic liver disease (non-NAFLD), including positive HBsAg, positive anti-HIV, or positive HCV RNA at screening, or a known history of HCV RNA or HBsAg positivity within 2 years prior to screening.
* Presence or history of ascites, variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis, hepatocellular carcinoma, or liver transplantation at screening and randomization.
* Presence or history of malignant tumors within 5 years (except basal cell carcinoma, squamous cell skin cancer, and any carcinoma in situ).
* Personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN2).
* History of acute pancreatitis within 180 days prior to screening, or a history of chronic pancreatitis.
* Presence or history of gastroparesis, severe gastroesophageal reflux disease, or prior bariatric surgery at screening and randomization.
* History or presence of type 1 diabetes.
* Occurrence of myocardial infarction, stroke, NYHA class IV heart failure, hospitalization due to unstable angina, or transient ischemic attack within 90 days prior to screening or during the screening-to-randomization window.
* Type 2 diabetes accompanied by uncontrolled and potentially unstable diabetic retinopathy or maculopathy.
* History of severe depression, suicidal ideation, or recent suicide attempts.
* Known or suspected allergy to the active ingredients or any excipients of the study drug.
* Females who are pregnant, lactating, planning a pregnancy, or of childbearing potential but not utilizing highly effective contraceptive methods.
* Participation in any approved or unapproved investigational drug clinical trial within 180 days prior to screening (defined as exposure to the investigational drug and inclusive of any post-treatment follow-up period).
* Prior participation in this trial (defined as having already undergone randomization).
* Known or suspected excessive alcohol consumption (females \> 20g/day, males \> 30g/day) or presence of alcohol dependence.
* Use of any GLP-1 receptor agonist (GLP-1RA) within 90 days prior to screening.
* Receipt of glucose-lowering drugs (except GLP-1RA), lipid-lowering drugs, or weight-loss drugs considered by the investigator to be at unstable doses within 90 days prior to screening.
* Any condition considered by the investigator to render the participant unsuitable for liver donation, or diseases/conditions that may compromise participant safety, pose safety hazards from substantial weight loss, or affect compliance with the protocol.
* The recipient designated to receive the liver graft is not a spouse or a direct or collateral blood relative within three generations, or the donation violates ethical, moral, legal, or regulatory codes.
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