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

What this study is testing ClinicalTrials.gov NCT07718126 ↗

Description as written by the study sponsor.

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.

Treatments tested

• 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.

• 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 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.