Body-weight Reduction Effect on Portal Hypertension in Compensated Cirrhosis (B-REACH)
2026. augusztus 30. frissítette: JinjunChen, The Second Affiliated Hospital of Chongqing Medical University
Efficacy and Safety of Mazdutide Injection for the Treatment of Overweight Patients With Compensated Cirrhosis and Clinically Significant Portal Hypertension
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.
A tanulmány áttekintése
Állapot
Még nincs toborzás
Körülmények
Beavatkozás / kezelés
Tanulmány típusa
Beavatkozó
Beiratkozás (Becsült)
50
Fázis
- Nem alkalmazható
Részvételi kritériumok
A kutatók olyan embereket keresnek, akik megfelelnek egy bizonyos leírásnak, az úgynevezett jogosultsági kritériumoknak. Néhány példa ezekre a kritériumokra a személy általános egészségi állapota vagy a korábbi kezelések.
Jogosultsági kritériumok
Tanulmányozható életkorok
- Felnőtt
- Idősebb felnőtt
Egészséges önkénteseket fogad
Nem
Leírás
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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 2.
- 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.
Tanulási terv
Ez a rész a vizsgálati terv részleteit tartalmazza, beleértve a vizsgálat megtervezését és a vizsgálat mérését.
Hogyan készül a tanulmány?
Tervezési részletek
- Elsődleges cél: Kezelés
- Kiosztás: N/A
- Beavatkozó modell: Egyetlen csoportos hozzárendelés
- Maszkolás: Nincs (Open Label)
Fegyverek és beavatkozások
Résztvevő csoport / kar |
Beavatkozás / kezelés |
|---|---|
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Kísérleti: Experimental: Mazdutide (2/4/6 mg Titration) SC QW
|
Mazdutide injection is a sterile, clear to almost colorless liquid formulated for subcutaneous administration.
It is supplied in three fixed-dose strengths for this study: 2 mg/0.5 mL, 4 mg/0.5 mL, and 6 mg/0.5 mL.
Participants assigned to this arm receive once-weekly subcutaneous injections over a 16-week active treatment period.
The regimen begins with a forced dose-titration phase: 2 mg weekly for the first 4 weeks, followed by 4 mg weekly for the next 4 weeks, and then 6 mg weekly for the final 8 weeks, provided the preceding dose is tolerated.
In cases of treatment-emergent adverse events (CTCAE grade ≥2 or intolerable grade 1), the investigator may temporarily withhold the dose, step down to the next lower dose level (6 mg→4 mg→2 mg), or permanently discontinue the drug.
After symptom resolution, gradual re-escalation (2 mg→4 mg→6 mg) may be attempted at the investigator's discretion.
|
Mit mér a tanulmány?
Elsődleges eredményintézkedések
Eredménymérő |
Intézkedés leírása |
Időkeret |
|---|---|---|
|
Percentage Change in Hepatic Venous Pressure Gradient (HVPG) from Baseline
Időkeret: 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).
|
Baseline (screening, Day -14 to -1) to Week 16 (End of Treatment, Day 112 ± 3 days)
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Másodlagos eredményintézkedések
Eredménymérő |
Intézkedés leírása |
Időkeret |
|---|---|---|
|
Proportion of Participants Achieving HVPG Response
Időkeret: Baseline to Week 16 (End of Treatment, Day 112 ± 3 days)
|
Proportion of participants with a reduction in HVPG of ≥10% from baseline, or a reduction to an absolute value of <10 mmHg at week 16.
HVPG is measured via hepatic vein catheterization in triplicate under fasting conditions.
|
Baseline to Week 16 (End of Treatment, Day 112 ± 3 days)
|
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Incidence of Hepatic Decompensation Events
Időkeret: Baseline up to Week 16 (End of Treatment)
|
Number of participants experiencing any first or recurrent decompensation event during the treatment period, including: overt ascites (requiring paracentesis or diuretic escalation), overt hepatic encephalopathy (West Haven grade ≥2), or gastroesophageal variceal bleeding (confirmed by endoscopy or imaging).
|
Baseline up to Week 16 (End of Treatment)
|
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Treatment Discontinuation Due to Adverse Events
Időkeret: Day 1 (First dose) to Week 16 (End of Treatment)
|
Number of participants who permanently discontinue study drug due to any adverse event (AE) during the 16-week treatment period, regardless of causality.
Reasons for discontinuation will be summarized by system organ class and preferred term.
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Day 1 (First dose) to Week 16 (End of Treatment)
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Change in Liver and Spleen Stiffness
Időkeret: Baseline to Week 16 (End of Treatment, Day 112 ± 3 days)
|
Absolute change (kPa) and percentage change in liver stiffness measurement (LSM) and spleen stiffness measurement (SSM) from baseline to week 16, assessed by vibration-controlled transient elastography (VCTE™, FibroScan®) under fasting conditions.
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Baseline to Week 16 (End of Treatment, Day 112 ± 3 days)
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Egyéb eredményintézkedések
Eredménymérő |
Intézkedés leírása |
Időkeret |
|---|---|---|
|
Liver stiffness measured by VCTE
Időkeret: Baseline to weeks 4, 8, 12, and 16 (Days 28, 56, 84, 112; ±3 days)
|
Change from baseline in liver stiffness assessed by Vibration-Controlled Transient Elastography (VCTE).
Unit of measure: kPa
|
Baseline to weeks 4, 8, 12, and 16 (Days 28, 56, 84, 112; ±3 days)
|
|
Spleen Stiffness measured by VCTE
Időkeret: Baseline to weeks 4, 8, 12, and 16 (Days 28, 56, 84, 112; ±3 days)
|
Change from baseline in spleen stiffness assessed by Vibration-Controlled Transient Elastography (VCTE).
Unit of measure: kPa.
|
Baseline to weeks 4, 8, 12, and 16 (Days 28, 56, 84, 112; ±3 days)
|
|
Liver Fat Content measured by Controlled Attenuation Parameter (CAP)
Időkeret: Baseline to weeks 4, 8, 12, and 16 (Days 28, 56, 84, 112; ±3 days)
|
Change from baseline in liver fat content assessed by CAP.
Unit of measure: dB/m.
|
Baseline to weeks 4, 8, 12, and 16 (Days 28, 56, 84, 112; ±3 days)
|
|
Liver Function Tests (ALT, AST, Bilirubin, Albumin)
Időkeret: Baseline to weeks 4, 8, 12, and 16 (Days 28, 56, 84, 112; ±3 days)
|
Change from baseline in serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total and direct bilirubin, and albumin.
These assessments have different units (ALT/AST in U/L; bilirubin in μmol/L or mg/dL; albumin in g/L) and will be reported individually without aggregation into a composite value.
|
Baseline to weeks 4, 8, 12, and 16 (Days 28, 56, 84, 112; ±3 days)
|
|
Coagulation Function (PT, INR, APTT)
Időkeret: Baseline to weeks 4, 8, 12, and 16 (Days 28, 56, 84, 112; ±3 days)
|
Change from baseline in prothrombin time (PT, in seconds), international normalized ratio (INR, dimensionless ratio), and activated partial thromboplastin time (APTT, in seconds).
These assessments with different units will be reported separately.
|
Baseline to weeks 4, 8, 12, and 16 (Days 28, 56, 84, 112; ±3 days)
|
|
Renal Function (eGFR)
Időkeret: Baseline to weeks 4, 8, 12, and 16 (Days 28, 56, 84, 112; ±3 days)
|
Change from baseline in estimated glomerular filtration rate calculated using the CKD-EPI or MDRD formula.
Unit of measure: mL/min/1.73m².
|
Baseline to weeks 4, 8, 12, and 16 (Days 28, 56, 84, 112; ±3 days)
|
|
Body Composition Indices (BMI, Waist-to-Hip Ratio, Waist-to-Height Ratio)
Időkeret: Baseline to weeks 4, 8, 12, and 16 (Days 28, 56, 84, 112; ±3 days)
|
Change from baseline in body composition indices.
Note on aggregation: Weight (kg) and height (m) will be combined to calculate BMI (kg/m²); waist circumference (cm) and hip circumference (cm) will be combined to calculate waist-to-hip ratio and waist-to-height ratio (both expressed as dimensionless ratios).
All derived indices will be reported individually.
|
Baseline to weeks 4, 8, 12, and 16 (Days 28, 56, 84, 112; ±3 days)
|
|
Fasting Glucose and Lipid Profile
Időkeret: Baseline to weeks 4, 8, 12, and 16 (Days 28, 56, 84, 112; ±3 days)
|
Change from baseline in fasting plasma glucose, total cholesterol, triglycerides, LDL-C, and HDL-C.
All assessments share the same unit of measure (mmol/L or mg/dL, depending on local laboratory standard) and will be reported as separate numerical values.
|
Baseline to weeks 4, 8, 12, and 16 (Days 28, 56, 84, 112; ±3 days)
|
|
Uric Acid
Időkeret: Baseline to weeks 4, 8, 12, and 16 (Days 28, 56, 84, 112; ±3 days)
|
Change from baseline in serum uric acid.
Unit of measure: μmol/L or mg/dL (as per local laboratory).
|
Baseline to weeks 4, 8, 12, and 16 (Days 28, 56, 84, 112; ±3 days)
|
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Urine Protein
Időkeret: Baseline to weeks 4, 8, 12, and 16 (Days 28, 56, 84, 112; ±3 days)
|
Change from baseline in urine protein concentration.
Unit of measure: mg/dL or g/24h (as per collection method).
|
Baseline to weeks 4, 8, 12, and 16 (Days 28, 56, 84, 112; ±3 days)
|
Együttműködők és nyomozók
Itt találhatja meg a tanulmányban érintett személyeket és szervezeteket.
Tanulmányi rekorddátumok
Ezek a dátumok nyomon követik a ClinicalTrials.gov webhelyre benyújtott vizsgálati rekordok és összefoglaló eredmények benyújtásának folyamatát. A vizsgálati feljegyzéseket és a jelentett eredményeket a Nemzeti Orvostudományi Könyvtár (NLM) felülvizsgálja, hogy megbizonyosodjon arról, hogy megfelelnek-e az adott minőség-ellenőrzési szabványoknak, mielőtt közzéteszik őket a nyilvános weboldalon.
Tanulmány főbb dátumok
Tanulmány kezdete (Becsült)
2026. szeptember 1.
Elsődleges befejezés (Becsült)
2029. május 31.
A tanulmány befejezése (Becsült)
2029. május 31.
Tanulmányi regisztráció dátumai
Először benyújtva
2026. augusztus 20.
Először nyújtották be, amely megfelel a minőségbiztosítási kritériumoknak
2026. augusztus 30.
Első közzététel (Tényleges)
2026. szeptember 1.
Tanulmányi rekordok frissítései
Utolsó frissítés közzétéve (Tényleges)
2026. szeptember 1.
Az utolsó frissítés elküldve, amely megfelel a minőségbiztosítási kritériumoknak
2026. augusztus 30.
Utolsó ellenőrzés
2026. augusztus 1.
Több információ
A tanulmányhoz kapcsolódó kifejezések
További vonatkozó MeSH feltételek
Egyéb vizsgálati azonosító számok
- 2026-IIT-SL-233
Terv az egyéni résztvevői adatokhoz (IPD)
Tervezi megosztani az egyéni résztvevői adatokat (IPD)?
NEM
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