Efficacy and Safety of Mazdutide Injection for the Treatment of Overweight Patients With Compensated Cirrhosis and Clinically Significant Portal Hypertension
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 50
- 主要终点
- Percentage Change in Hepatic Venous Pressure Gradient (HVPG) from Baseline
研究概览
简要总结
Obesity and metabolic abnormalities accelerate decompensation in compensated cirrhosis, driven by clinically significant portal hypertension (CSPH, HVPG≥10 mmHg). Lifestyle-induced weight loss can lower portal pressure, but pharmacological options are limited. Mazdutide, a dual GLP-1/glucagon receptor agonist, has proven weight-loss and glycaemic benefits, yet its safety and efficacy in cirrhosis with portal hypertension are unknown. This investigator-initiated, single-arm, open-label, exploratory trial evaluates whether mazdutide can safely reduce portal pressure in overweight patients with compensated cirrhosis and CSPH.
The main questions it aims to answer are:
Does 16-week mazdutide treatment reduce HVPG (percentage change from baseline)? What adverse events occur, and is the drug tolerated?
Participants will:
Receive mazdutide SC injection once weekly for 16 weeks, titrated from 2 mg to 4 mg to 6 mg (if tolerated), with dose adjustment for intolerance.
Undergo HVPG at baseline and week 16 (primary endpoint). Have FibroScan® (liver/spleen stiffness, CAP) at baseline and weeks 4, 8, 12, 16.
Provide blood samples for liver, renal, glucose, lipid, and coagulation tests at each visit.
Undergo body composition, handgrip strength, and nutritional assessments to monitor muscle mass.
Attend clinic visits every 4 weeks during treatment and one follow-up visit 4 weeks post-treatment.
Key eligibility: Adults 18-75 with compensated cirrhosis (viral, MASLD, or alcohol-related), HVPG≥10 mmHg, BMI≥28 or ≥26 with comorbidities, stable weight, and stable carvedilol/propranolol if used. Exclude prior decompensation, HCC, CTP≥B8, eGFR<60, mazdutide contraindications, active infection, uncontrolled hepatitis, portal vein thrombosis, etc.
Endpoints: Primary - % change in HVPG. Secondary - HVPG response (≥10% decrease or <10 mmHg), decompensation events, treatment discontinuation due to AEs. Exploratory - changes in stiffness, liver fat, metabolic parameters, body composition, nutrition.
Safety: AEs (CTCAE v5.0), labs, vitals, with special monitoring for GI symptoms, dehydration, renal function, hepatic encephalopathy, muscle loss, pancreatitis, and gallbladder events.
Sample size and analysis: 50 patients. Primary endpoint analysed by paired t-test or Wilcoxon (α=0.05, two-sided) in FAS and PPS. Secondary endpoints mainly descriptive; key secondary tested for support. Subgroup analyses planned if feasible.
Study duration: 20 weeks (2-week screening, 16-week treatment, 4-week follow-up). Conducted at Second Affiliated Hospital of Chongqing Medical University, China. Ethics approved, informed consent required. This study will provide first evidence on mazdutide for portal hypertension in overweight cirrhosis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 18 to 75 years (inclusive), male or female.
- •Documented etiology of chronic liver disease, limited to chronic hepatitis B, chronic hepatitis C, metabolic dysfunction-associated steatotic liver disease (MASLD), or alcohol-related liver disease.
- •Cirrhosis confirmed by imaging (ultrasound, CT, or MRI), or pathology showing F3/F4 fibrosis, or liver stiffness measurement (LSM) ≥15 kPa by vibration-controlled transient elastography (VCTE).
- •Hepatic venous pressure gradient (HVPG) ≥10 mmHg.
- •Body mass index (BMI) ≥28 kg/m², or BMI ≥26 kg/m² with at least one weight-related comorbidity (e.g., hyperglycemia, hypertension, dyslipidemia, fatty liver, obstructive sleep apnea syndrome).
- •Stable body weight over the past 6 months, defined as weight fluctuation <3 kg.
- •For patients with gastroesophageal varices requiring carvedilol or propranolol, the dose must have been stable for at least 3 months with no planned dose adjustments during the trial.
- •Voluntarily signed informed consent form.
排除标准
- •Concurrent hepatocellular carcinoma or other malignancies (excluding cured basal cell carcinoma of the skin).
- •Prior history of clinically significant decompensation events (grade 2/3 ascites, overt hepatic encephalopathy, or gastroesophageal variceal bleeding).
- •Progressive jaundice during the screening period.
- •Hepatic impairment defined as Child-Turcotte-Pugh (CTP) score ≥B8 at screening.
- •Moderate to severe renal impairment (eGFR <60 mL/min) or current renal replacement therapy.
- •Contraindications to mazdutide: known allergy, personal or family history of medullary thyroid carcinoma, or multiple endocrine neoplasia syndrome type
- •Previous or current use of other weight-loss interventions (e.g., bariatric surgery, endoscopic bariatric procedures, other weight-loss drugs).
- •Participation in another interventional clinical trial within 3 months prior to screening, or previous treatment with mazdutide.
- •Active infection at screening.
- •For alcohol-related cirrhosis: alcohol abstinence <6 months or ongoing alcohol consumption. For viral cirrhosis (hepatitis B/C): failure to achieve virologic suppression (HBV-DNA <100 IU/mL for hepatitis B; for hepatitis C, HCV-RNA below the lower limit of detection after >12 weeks of antiviral therapy).
- •Prior portal-systemic shunt surgery (e.g., splenectomy).
- •Previous orthotopic liver transplantation.
- •Known portal vein thrombosis.
- •Contraindications to trial assessments, e.g., inability to undergo HVPG measurement.
- •Pregnancy or breastfeeding, or unwillingness to use investigator-approved contraception during the study and for 6 months after the study end.
- •Psychiatric or cognitive disorders that interfere with study compliance.
- •Any other condition judged by the investigator to make the participant unsuitable for participation.
研究组 & 干预措施
Experimental: Mazdutide (2/4/6 mg Titration) SC QW
干预措施: Mazdutide injection (Drug)
结局指标
主要结局
Percentage Change in Hepatic Venous Pressure Gradient (HVPG) from Baseline
时间窗: Baseline (screening, Day -14 to -1) to Week 16 (End of Treatment, Day 112 ± 3 days)
Percentage change in HVPG (measured in mmHg) from baseline to week 16. HVPG is calculated as the difference between wedged hepatic venous pressure (WHVP) and free hepatic venous pressure (FHVP), measured via hepatic vein catheterization under fasting conditions. A negative percentage change indicates a reduction in portal pressure. HVPG measurements will be performed in triplicate through the same hepatic vein, preferably in the morning, at baseline (screening period) and at week 16 (end-of-treatment visit, Day 112). All measurements follow a standardized procedure by experienced operators (≥25 HVPG measurements annually).
次要结局
- Proportion of Participants Achieving HVPG Response(Baseline to Week 16 (End of Treatment, Day 112 ± 3 days))
- Incidence of Hepatic Decompensation Events(Baseline up to Week 16 (End of Treatment))
- Treatment Discontinuation Due to Adverse Events(Day 1 (First dose) to Week 16 (End of Treatment))
- Change in Liver and Spleen Stiffness(Baseline to Week 16 (End of Treatment, Day 112 ± 3 days))
研究者
JinjunChen
Prof
The Second Affiliated Hospital of Chongqing Medical University