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Trial · Interventional

RecruitingPhase 4Registry data

Pre-hepatectomy Rehabilitation in Obese MASLD-Complicated Living Liver Donors With Mazdutide (PRIME)

Short name PRIME

Overview

Status
Recruiting
Phase
Phase 4
Enrollment
60 participants (estimated)
Sponsor
West China Hospital · Other
Design
Randomized · Quadruple masking
Countries
1 country

China

Start
1 Sept 2026
Primary completion
28 Feb 2029 (estimated)
Completion
31 Aug 2029 (estimated)
First posted
21 Jul 2026
Last update posted
23 Sept 2026
Conditions
Metabolic Dysfunction-Associated Steatohepatitis · Hepatic Steatosis · Living Liver Donors

Timeline

1 trial · 1 ongoing

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
20262027202820292030
  1. Ph 4

    PRIME

    NCT07718126

    1 Sept 2026 to est. 31 Aug 2029

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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 of mazdutide can significantly increase the proportion of donors achieving histological resolution of hepatic steatosis without the worsening of fibrosis within 12 weeks. The study ultimately aims to provide high-quality evidence for a rapid, safe, and effective surgical prehabilitation protocol to expand the living donor pool and optimize perioperative outcomes for both donors and recipients.

Interventions

  • MazdutideDrug
  • Placebo (Normal Saline)Drug
  • Lifestyle OptimizationBehavioral

Arms2

  • Experimental

    GLP-1/GCG receptor dual agonist plus lifestyle optimization (GG Group)

    Subcutaneous injection of mazdutide once weekly following a 12-week dose-escalation regimen: 2 mg q1w for Weeks 1-2, 4 mg q1w for Weeks 3-4 (if gastrointestinal tolerated), and a target dose of 6 mg q1w from Week 5 to Week 12 (if gastrointestinal tolerated). Standardized lifestyle optimization consists of an energy-restricted diet (deficit of 500-750 kcal/day, total daily intake \<=1500 kcal/day) and structured physical exercise (\>=150 minutes/week of moderate-to-high intensity exercise). A mandatory 1-week drug washout period is enforced prior to surgery.

  • Placebo comparator

    Lifestyle optimization only (LL group)

    Subcutaneous injection of a matching placebo once weekly with identical appearance, volume, and injection device for 12 weeks. Standardized lifestyle optimization is identical to the experimental group, consisting of an energy-restricted diet (deficit of 500-750 kcal/day, total daily intake \<=1500 kcal/day) and structured physical exercise (\>=150 minutes/week of moderate-to-high intensity exercise). A matching 1-week placebo washout period is enforced prior to surgery to maintain blinding.

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Proportion of Participants Achieving Resolution of MASLD Without Worsening of Liver Fibrosis (ROM)

    Time frame · From randomization (Week 0) to Week 12

    Registry description

    Percentage of participants who achieve histological resolution of MASLD. Resolution is defined based on the second liver biopsy as a NAFLD Activity Score (NAS) steatosis subscore \<= 1, a hepatocyte ballooning subscore = 0, and a lobular inflammation subscore \<= 1. Additionally, to meet the criteria for resolution, there must be no increase in the total NAS, hepatocyte ballooning, or lobular inflammation subscores, and no worsening of liver fibrosis compared to the baseline liver biopsy.

Secondary outcomes(13)
  1. Proportion of Participants Achieving Ultrasound-Assessed Improvement of Hepatic Steatosis (uIOS)

    Time frame · From randomization (Week 0) up to Week 12

    Registry description

    Percentage of participants who achieve improvement of hepatic steatosis evaluated by FibroScan®. Improvement is defined as the Controlled Attenuation Parameter (CAP) dropping to \< 268 dB/m.

  2. Proportion of Participants Achieving Imaging-Assessed Improvement of Hepatic Steatosis (iIOS)

    Time frame · From randomization (Week 0) up to Week 12

    Registry description

    Percentage of participants who achieve improvement of hepatic steatosis evaluated by Magnetic Resonance Imaging (MRI). Improvement is defined as the MRI Proton Density Fat Fraction (MRI-PDFF) dropping to \< 15%.

  3. Proportion of Participants Achieving Improvement of MASLD Without Worsening of Liver Fibrosis (IOM)

    Time frame · From randomization (Week 0) up to Week 12

    Registry description

    Percentage of participants achieving MASLD improvement evaluated by liver biopsy. It is defined as a decrease in the total NAS by \>= 2 or a total NAS \<= 3, with a steatosis subscore \<= 1, while maintaining no increase in subscores for hepatocyte ballooning or lobular inflammation, and no worsening of liver fibrosis.

  4. Proportion of Participants Achieving Improvement of Hepatic Steatosis Without Worsening of MASLD (IOS)

    Time frame · From randomization (Week 0) up to Week 12

    Registry description

    Percentage of participants achieving steatosis improvement evaluated by liver biopsy. It is defined as a decrease in the total NAS by \>= 1 and a NAS steatosis subscore \<= 1, while maintaining no increase in total NAS, hepatocyte ballooning, or lobular inflammation subscores, and no worsening of liver fibrosis.

  5. Proportion of Participants Successfully Completing Liver Donation (SCD)

    Time frame · From randomization (Week 0) up to Week 24

    Registry description

    Percentage of participants who successfully fulfill the clinical criteria for living donor liver transplantation and complete the liver procurement surgery.

  6. Percentage Change from Baseline in Body Weight

    Time frame · From randomization (Week 0) up to Week 12

    Registry description

    Relative change in body weight measured in percentage using calibrated electronic scales under fasting conditions.

  7. Percentage Change from Baseline in Body Mass Index (BMI)

    Time frame · From randomization (Week 0) up to Week 12

    Registry description

    Relative change in BMI calculated as weight in kilograms divided by height in meters squared.

  8. Percentage Change from Baseline in Body Fat Percentage

    Time frame · From randomization (Week 0) up to Week 12

    Registry description

    Relative change in body fat percentage evaluated using the Bioelectrical Impedance Analysis (BIA) method.

  9. Percentage Change from Baseline in Visceral Fat Content

    Time frame · From randomization (Week 0) up to Week 12

    Registry description

    Relative change in visceral fat volume and content quantitatively assessed via abdominal MRI scans.

  10. Daily Net Energy Intake During the Treatment Period

    Time frame · From randomization (Week 0) up to Week 12

    Registry description

    Daily net energy intake calculated based on the total daily energy expenditure estimated by smart fitness trackers minus the daily dietary calorie intake self-reported via electronic questionnaires.

  11. Time to Ultrasound-Assessed Hepatic Steatosis Improvement

    Time frame · From randomization (Week 0) up to Week 12

    Registry description

    The number of days from randomization to the first documentation of hepatic steatosis improvement, defined as a CAP score \< 268 dB/m via regular FibroScan® assessments.

  12. Time to Successful Liver Donation

    Time frame · From randomization (Week 0) up to Week 24

    Registry description

    The number of days from randomization to the date of the successful liver procurement surgery.

  13. Change from Baseline in Health-Related Quality of Life (HRQoL) Score

    Time frame · From randomization (Week 0) up to Week 12

    Registry description

    Change in patient-reported quality of life assessed using the validated Chinese version of the Short Form-36 (SF-36) questionnaire. Total scores range from 0 to 100 for each subscale, with higher scores representing better health status and quality of life.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

No results are posted for this trial.

A trial that is still running, or that stopped early, may post results later.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years up to 60 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
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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