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

NCT07718126 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: 2026-1206
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Metabolic Dysfunction-Associated Steatohepatitis; Hepatic Steatosis; Living Liver Donors

Keywords

Mazdutide; GLP-1/GCG receptor dual agonist; Living Donor Liver Transplantation; Prehabilitation; MASLD; Organ Donation; Preoperative Weight Loss

Outcome Measures

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.

  From randomization (Week 0) to Week 12

Secondary Outcomes (17)

• Proportion of Participants Achieving Ultrasound-Assessed Improvement of Hepatic Steatosis (uIOS)

  From randomization (Week 0) up to Week 12

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

  From randomization (Week 0) up to Week 12

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

  From randomization (Week 0) up to Week 12

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

  From randomization (Week 0) up to Week 12

• Proportion of Participants Successfully Completing Liver Donation (SCD)

  From randomization (Week 0) up to Week 24

Other Outcomes (4)

• Peak Serum AST and ALT Levels in Recipients Post-Transplantation

  From liver transplantation surgery up to post-operative Week 2

• Time to Serum TBil Normalization in Recipients Post-Transplantation

  From liver transplantation surgery up to post-operative Week 2

• Time to INR Normalization in Recipients Post-Transplantation

  From liver transplantation surgery up to post-operative Week 2

Study Arms (2)

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

EXPERIMENTAL

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.

Drug: Mazdutide; Behavioral: Lifestyle Optimization

Lifestyle optimization only (LL group)

PLACEBO COMPARATOR

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.

Drug: Placebo (Normal Saline); Behavioral: Lifestyle Optimization

Interventions

Mazdutide DRUG

Active 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.

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

Placebo (Normal Saline) DRUG

Inactive 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 only (LL group)

Lifestyle Optimization BEHAVIORAL

Standardized 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.

GLP-1/GCG receptor dual agonist plus lifestyle optimization (GG Group); Lifestyle optimization only (LL group)

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• West China Hospital: lead
• Beijing Friendship Hospital: collaborator
• Anhui Provincial Hospital: collaborator
• The Second Affiliated Hospital of Chongqing Medical University: collaborator
• First Affiliated Hospital of Chongqing Medical University: collaborator

Study Sites (3)

Anhui Provincial Hospital (The First Affiliated Hospital of USTC)

Hefei, Anhui, 230036, China

Location

Beijing Friendship Hospital, Capital Medical University

Beijing, Beijing Municipality, 100050, China

Location

West China Hospital, Sichuan University

Chengdu, Sichuan, 610041, China

Location

MeSH Terms

Conditions

Fatty Liver

Interventions

mazdutide; Saline Solution

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Central Study Contacts

Kunlin Xie, MD, PhD

CONTACT

8618980607259; xiekun@scu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate professor

Study Record Dates

• First Submitted: July 16, 2026
• First Posted: July 21, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): August 31, 2028
• Study Completion (Estimated): August 31, 2028
• Last Updated: July 21, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: The data that support the findings of this study are available from the corresponding author upon reasonable request.
• Access Criteria: The data that support the findings of this study are available from the corresponding author upon reasonable request.

Locations

CN (3)