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Metabolic Dysfunction-Associated SteatohepatitisPhase 4PRIMENCT07718126

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

A Phase 4 study testing Mazdutide and Lifestyle Optimization in people with Metabolic Dysfunction-Associated Steatohepatitis and Hepatic Steatosis, run by West China Hospital at 4 sites in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 to 60 years
What is being tested?
Mazdutide and Lifestyle Optimization
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
60 participants
Where
4 sitesChina
Study dates
1 Sep 2026to 31 Aug 2029
Phase
Phase 4
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 60 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

4 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Kunlin Xie, MD, PhD contact

8618980607259

xiekun@scu.edu.cn

China4 sites, 4 recruiting

  • Beijing Friendship Hospital, Capital Medical University

    Beijing, Beijing Municipality, 100050

    Lin Wei, MD, 8618610932626, weilin@ccmu.edu.cn

    Zhijun Zhu, MD

    Not yet recruiting

  • West China Hospital, Sichuan University

    Chengdu, Sichuan, 610041

    Kunlin Xie, MD, PhD, 8618980607259, xiekun@scu.edu.cn

    Hong Wu, MD

    Not yet recruiting

  • The First Affiliated Hospital of Chongqing Medical University

    Chongqing, Chongqing Municipality, 400016

    Jianguo Qiu, MD, 8615703042673, qiujianguo456@163.com

    Jingyang Gu, MD

    Recruiting

  • Anhui Provincial Hospital (The First Affiliated Hospital of USTC)

    Hefei, Anhui, 230036

    Shugeng Zhang, MD, 8615945965885, zsg0517@ustc.edu.cn

    Shugeng Zhang, MD

    Not yet recruiting

Other trials in China

About this study

Official title: Short-term Mazdutide Plus Lifestyle Intervention Versus Placebo for Pre-hepatectomy Prehabilitation in Living Liver Donors With MASLD: A Multicenter, Randomized, Double-blind, Placebo-controlled 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.

Read the detailed description

Background and Rationale:

Hepatic steatosis significantly elevates perioperative complications in major abdominal surgeries. In living donor liver transplantation (LDLT), macrovesicular steatosis exceeding 30% renders potential donors ineligible due to severe ischemia-reperfusion injury risks in recipients and impaired remnant liver regeneration in donors. Traditional prehabilitation strategies relying solely on lifestyle changes or low-calorie diets often fail to achieve satisfactory histological reversal within the critical, time-sensitive pre-operative window. Mazdutide, a dual agonist of GLP-1 and glucagon (GCG) receptors, has demonstrated powerful synergistic effects in rapid weight reduction and rapid hepatic fat clearance by simultaneously suppressing appetite and activating hepatic lipolysis. This trial aims to validate whether short-term mazdutide intervention can serve as an aggressive prehabilitation tool to accelerate donor downstaging.

Study Design and Procedures:

This is a prospective, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial conducted in major transplant centers. The study consists of two parts: Part 1 spans from screening to the liver procurement surgery (up to 24 weeks), and Part 2 covers post-operative follow-up up to 1 year.

Potential donors will undergo a rigorous two-step screening process:

  1. Non-invasive screening: Assessment of body mass index (BMI >= 24 kg/m²) and controlled attenuation parameter via FibroScan (CAP >= 268 dB/m).
  2. Histological confirmation: A baseline liver biopsy (Liver Biopsy 1) demonstrating MASLD with a NAFLD Activity Score (NAS) >= 3 and a steatosis subscore >= 2, strictly excluding any degree of liver fibrosis.

Eligible participants will be randomized (1:1) into:

  • Experimental Group (GG Group): Mazdutide subcutaneous injections once weekly, following a dose-escalation regimen: 2mg for Weeks 1-2, 4mg for Weeks 3-4, and a target dose of 6mg from Week 5 to Week 12.
  • Control Group (LL Group): Matching placebo injections once weekly. Both groups will receive identical, standardized counseling on an energy-restricted diet (deficit of 500-750 kcal/day, total intake <= 1500 kcal/day) and structured physical exercise (>= 150 minutes/week of moderate-to-high intensity sport). Compliance will be monitored via electronic diaries and smart wearable fitness trackers.

Efficacy and Safety Endpoints:

At Week 12 (or earlier if triggered by regular FibroScan text assessments indicating steatosis resolution), a second liver biopsy (Liver Biopsy 2) and abdominal magnetic resonance imaging proton density fat fraction (MRI-PDFF) will be completed to evaluate the primary endpoint: resolution of hepatic steatosis without worsening of MASLD.

For donors successfully meeting the transplantation criteria, a mandatory 1-week drug washout period will be enforced before surgery to mitigate potential anesthesia risks associated with delayed gastric emptying. On the day of surgery, an ultrasound assessment of gastric volume will be performed prior to anesthesia induction.

Exploratory analysis in Part 2 will dynamically track the remnant liver regeneration rate in donors (via CT volumetry) and early graft function (AST/ALT peaks, TBil, and INR recovery profiles) as well as long-term quality of life (SF-36) in recipients up to 1 year post-transplantation.

Being tested
Mazdutide, Placebo (Normal Saline), Lifestyle Optimization
Keywords
Mazdutide, GLP-1/GCG receptor dual agonist, Living Donor Liver Transplantation, Prehabilitation, MASLD, Organ Donation, Preoperative Weight Loss
Medical subject headings
Fatty Liver

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MazdutideDrug

    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 OptimizationBehavioural

    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.

Study groups in NCT07718126
Study groupRoleWhat they receive
GLP-1/GCG receptor dual agonist plus lifestyle optimization (GG Group)ExperimentalSubcutaneous 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.
Receives: Drug: Mazdutide; Behavioral: Lifestyle Optimization
Lifestyle optimization only (LL group)Placebo comparatorSubcutaneous 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.
Receives: Drug: Placebo (Normal Saline); Behavioral: Lifestyle Optimization

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: From randomization (Week 0) to Week 12

Secondary outcomes (13)

  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.

    Measured: From randomization (Week 0) up to Week 12

  2. 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%.

    Measured: From randomization (Week 0) up to Week 12

  3. 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.

    Measured: From randomization (Week 0) up to Week 12

  4. 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.

    Measured: From randomization (Week 0) up to Week 12

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

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

    Measured: From randomization (Week 0) up to Week 24

  6. Percentage Change from Baseline in Body Weight

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

    Measured: From randomization (Week 0) up to Week 12

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

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

    Measured: From randomization (Week 0) up to Week 12

  8. Percentage Change from Baseline in Body Fat Percentage

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

    Measured: From randomization (Week 0) up to Week 12

  9. Percentage Change from Baseline in Visceral Fat Content

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

    Measured: From randomization (Week 0) up to Week 12

  10. Daily Net Energy Intake During the Treatment Period

    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.

    Measured: From randomization (Week 0) up to Week 12

  11. Time to Ultrasound-Assessed Hepatic Steatosis Improvement

    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.

    Measured: From randomization (Week 0) up to Week 12

  12. Time to Successful Liver Donation

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

    Measured: From randomization (Week 0) up to Week 24

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

    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.

    Measured: From randomization (Week 0) up to Week 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Jul 2026
  2. Study start1 Sep 2026
  3. Primary completion28 Feb 2029 (estimated)
  4. Study completion31 Aug 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07718126
Sponsor's protocol ID
2026-0674
Acronym
PRIME
Status last verified
Sep 2026
First submitted
16 Jul 2026
Last updated
23 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: The data that support the findings of this study are available from the corresponding author upon reasonable request.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Mazdutide and Lifestyle Optimization in people with Metabolic Dysfunction-Associated Steatohepatitis and Hepatic Steatosis, run by West China Hospital at 4 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 23 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Kunlin Xie, MD, PhD (8618980607259, xiekun@scu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of Participants Achieving Resolution of MASLD Without Worsening of Liver Fibrosis (ROM) (time frame: From randomization (Week 0) to Week 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07718126.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2026.

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