Pre-hepatectomy Rehabilitation in Obese MASLD-Complicated Living Liver Donors With Mazdutide (PRIME)
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18-60
SponsorWest China Hospital
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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).
Disqualifiers
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.
Trial design
Design model
Parallel
Treatments tested in this trial
Mazdutide
DrugActive drug intervention consisting of a novel GLP-1/GCG receptor dual agonist solution (Mazdutide) administered via subcutaneous injection once weekly using a single-use prefilled automatic injection pen. The dosing schedule follows a 12-week step-up titration regimen starting at 2 mg q1w for Weeks 1-2, increasing to 4 mg q1w for Weeks 3-4 if gastrointestinal tolerated, and reaching a target dose of 6 mg q1w from Week 5 to Week 12 if gastrointestinal tolerated. For participants with intolerable gastrointestinal adverse events, the titration cycle can be prolonged to 3 weeks, or they are permitted to maintain a lower tolerated dose based on multidisciplinary team consensus. To ensure surgical safety, this prehabilitation protocol enforces a mandatory 1-week drug washout period prior to hepatectomy, followed by a preoperative gastric ultrasound assessment by an anesthesiologist to rule out aspiration risks.
Placebo (Normal Saline)
DrugInactive comparator intervention consisting of a matching placebo (normal saline) solution administered via subcutaneous injection once weekly. To strictly maintain the double-blind design, the placebo features an identical appearance, volume, and automatic prefilled injection pen delivery device. The administration schedule, dose escalation simulation steps, and the mandatory 1-week pre-operative drug washout period mirror the experimental mazdutide group exactly to maintain the blinding integrity prior to the hepatectomy.
Lifestyle Optimization
BehavioralStandardized lifestyle optimization provided to both groups, consisting of an calorie-restricted diet (CRD) and structured physical exercise. The CRD targets a daily calorie deficit of 500 to 750 kcal, with a total daily intake not exceeding 1500 kcal (1000-1200 kcal for females; 1200-1500 kcal for males). The structured exercise requires at least 5 days per week, totaling \>=150 minutes of moderate-to-high intensity aerobic training with a daily energy expenditure \>=150 kcal. Adherence is tracked objectively using a provided smart fitness tracker and daily electronic diaries without mandatory enforcement.
Treatment groups
60 Participants
are divided into 2 treatment groupsGroup A: GLP-1/GCG receptor dual agonist plus lifestyle optimization (GG Group)Experimental treatment 2 interventions
Group B: Lifestyle optimization only (LL group)Placebo comparator 2 interventions
Trial outcomes
Primary outcomes
1
Proportion of Participants Achieving Resolution of MASLD Without Worsening of Liver Fibrosis (ROM)
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.
Time frame
From randomization (Week 0) to Week 12Secondary outcomes
1
Proportion of Participants Achieving Ultrasound-Assessed Improvement of Hepatic Steatosis (uIOS)
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.
Time frame
From randomization (Week 0) up to Week 122
Proportion of Participants Achieving Imaging-Assessed Improvement of Hepatic Steatosis (iIOS)
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%.
Time frame
From randomization (Week 0) up to Week 123
Proportion of Participants Achieving Improvement of MASLD Without Worsening of Liver Fibrosis (IOM)
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.
Time frame
From randomization (Week 0) up to Week 124
Proportion of Participants Achieving Improvement of Hepatic Steatosis Without Worsening of MASLD (IOS)
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.
Time frame
From randomization (Week 0) up to Week 12Other outcomes
1
Peak Serum AST and ALT Levels Post-Hepatectomy
The maximum serum concentration values of AST and ALT recorded during the donor's post-operative hospitalization period.
Time frame
From liver procurement surgery up to post-operative Week 22
Time to Serum TBil Normalization Post-Hepatectomy
The number of days from the liver procurement surgery until the serum total bilirubin level drops back to the normal reference range, defined as \<= 17.1 μmol/L (1 mg/dL).
Time frame
From liver procurement surgery up to post-operative Week 23
Time to INR Normalization Post-Hepatectomy
The number of days from the liver procurement surgery until the international normalized ratio (INR) returns to the reference range of 0.8 to 1.5.
Time frame
From liver procurement surgery up to post-operative Week 24
Remnant Liver Volume After Liver Procurement Surgery
Absolute volume of the remnant liver measured in mL using multi-slice spiral abdominal contrast-enhanced CT scans.
Time frame
From liver procurement surgery up to post-operative Week 4Sponsors and contacts
Click on the lead sponsor to view all of their trials.
West China Hospital
Lead sponsor
Beijing Friendship Hospital
Collaborator
Anhui Provincial Hospital
Collaborator
First Affiliated Hospital of Chongqing Medical University
Collaborator
Source ClinicalTrials.gov