NCT06374875Toboroz4. fázis

Fibrosis Lessens After Metabolic Surgery

A Prospective Multicenter International Randomized Controlled Trial Comparing Surgical and Medical Therapies in the Treatment of Advanced Metabolic Dysfunction Associated Steatohepatitis

Forrás: ClinicalTrials.gov · Utoljára frissítve: 2026. júl. 31.

Rövid összefoglaló (regiszter, angolul)

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), a major global public health concern, is commonly associated with obesity, diabetes, and dyslipidemia. MASLD is currently the most common cause of chronic liver disease affecting about 80% of people with obesity, ranging from simple fat deposits in the liver to Metabolic Dysfunction-Associated Steatohepatitis (MASH), cellular injury, advanced fibrosis, cirrhosis, or hepatocellular carcinoma. Patients with MASH are also at risk for cardiovascular disease and mortality. There is no universally approved medication for MASH. Weight loss remains the cornerstone of MASH treatment. Patients meeting the inclusion and exclusion criteria and who give informed consent will be enrolled in the trial and undergo the baseline liver biopsy (if none available). Approximately 120 patients with MASH and liver fibrosis (F1-F4 in baseline liver biopsy) will be randomized in a 1:1 ratio to metabolic surgery or medical treatment (incretin-based therapies ± other medical therapies for MASH) and followed for 2 years at which time a repeat liver biopsy will be performed for the assessment of the primary end point.

Állapot (regiszter): Toboroz
Fázis (regiszter): 4. fázis
Vizsgálattípus: Beavatkozással járó
Résztvevők száma: 120 (tervezett)
Első benyújtás: 2024. ápr. 16.
Kezdés: 2024. júl. 11.
Elsődleges befejezés: 2029. máj. 31.
Fő szponzor: The Cleveland Clinic
Betegségek: Elhízás, Zsírmáj (MASLD/MASH)
NCT-szám: NCT06374875

Mit vállalsz

Vizsgálat típusa: Beavatkozással járó · 4. fázis
Tervezett résztvevők: 120
2024. júl. 11. és az elsődleges befejezés (2029. máj. 31.) között
22 helyszín, 13 országban
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Entry into the study would require that the patient:
Is a candidate for general anesthesia
Is eligible for metabolic surgery (RYGB or SG) based on the ASMBS/IFSO 2022 guidelines
Has insurance coverage for metabolic surgery (the requirements may vary in each country)
Is ≥18 and ≤75 years old at the time of signing the informed consent
Has a BMI ≥35 and ≤70 kg/m2 at the time of first study visit
FIB-4 ≥ 1.3
At least one of the following 5 criteria suggesting presence of advanced fibrosis:
- LSM ≥ 12 kPa by VCTE using FibroScan®
- LSM ≥ 12 kPa by SWE
- LSM ≥ 1.7 m/s by ARFI
- LSM ≥ 3.63 kPa MRE
- ELF score ≥ 9.8
Patients with and without T2DM are eligible for the study. Patients with T2DM should have been on a stable dose of anti-diabetic medication (including insulin but not semaglutide or tirzepatide or liraglutide) for at least 3 months prior to entry, with glycated hemoglobin (HbA1c) ≤12%.
Self-reported stable weight in 6 months before the first study visit (no weight loss \>10% within 6 months prior to the first study visit)
- In patients with a historical noninvasive tests or liver biopsy, weight loss of no more than 10% is allowed from 6 months prior to the historical tests until the first study visit
Has the ability and willingness to participate in the study, provide informed consent, and agree to any of the arms involved in the study
Can understand the options and comply with the requirements of each arm, including one liver biopsy performed during the screening period (if no adequate biopsy within 12 months before screening is available) and one liver biopsy after 2-years
Has a negative urine pregnancy test at the first and at the randomization visits for women of childbearing potential.
Women of childbearing age must agree to use reliable method of contraception for 2 years
- 8.2 Exclusion Criteria
- Patients who meet the following criteria will be excluded from the study:
Known history of other chronic liver diseases (drug induced, viral hepatitis, autoimmune, and genetic):
- Hepatitis B as detected by presence of hepatitis B surface antigen (HBsAg)
- Hepatitis C as detected by presence of hepatitis C virus (HCV) RNA (in case the screening test for hepatitis C is positive, the confirmative test is decisive)
- Autoimmune liver disease as diagnosed by antibodies or compatible liver histology
- Primary biliary cirrhosis as defined by the presence of at least 2 criteria (elevated alkaline phosphatase, presence of anti-mitochondrial antibody, and histologic evidence of nonsuppurative destructive cholangitis and destruction of interlobular bile ducts)
- Primary sclerosing cholangitis
- Wilson's disease as diagnosed by low ceruloplasmin or compatible liver histology
- Alpha-1-antitrypsin deficiency as diagnosed by alpha1-antitrypsin level or liver histology
- Hemochromatosis as diagnosed by HFE mutations (C282Y, H63D), ferritin and transferrin saturation levels, or presence of 3+ or 4+ stainable iron on liver biopsy
- Drug-induced liver disease diagnosed by medical history
- Known bile duct obstruction
- Suspected or proven liver cancer
Weight change \>10% within 6 months prior to the first study visit or prior to the historical liver biopsy
Treatment with semaglutide, tirzepatide, or liraglutide (for obesity or for T2DM) \<90 days before the first study visit.
- However, patients are allowed to participate if they have been on a low dose (or are on older generation GLP-1 agonists) and have lost less than 10% of their body weight since starting the medication.
Type 1 diabetes or autoimmune diabetes
Known cases of human immunodeficiency virus infection
Prior bariatric and metabolic surgery of any kind
- Reversed procedures such as gastric band or intragastric balloon that have been removed at least 3 months prior to the first study visit are allowed.
Prior complex foregut surgery including any esophageal and gastric surgeries, anti-reflux procedures, biliary diversion, and complex trauma surgery
Any surgery requiring general anesthesia within 1 month prior to signing the consent
History of solid organ transplant
Severe pulmonary disease defined as FEV1 \< 50% of predicted value
Significant cardiac or atherosclerotic disease (planned to undergo cardiac, coronary, carotid, or peripheral artery revascularization procedures in the next 12 months)
Severe uncompensated cardiopulmonary disease leading to American Society of Anesthesiologists Class IV or V
Classified as New York Heart Association Class IV
Left ventricular ejection fraction \<25% at the time of screening
Myocardial infarction, unstable angina, stroke, heart surgery, coronary stent placement in the past 6 months
Chronic renal insufficiency with eGFR below 30 mL/min/1.73 m2, or being on dialysis
Presence of large hiatal hernia (\>7 cm)
Presence of Crohn's disease
Psychiatric disorders including (but not limited to) dementia, active psychosis, severe depression requiring 3 or more medications, history of suicide attempts, active alcohol, or substance abuse within the previous 12 months that in the opinion of the investigators could disqualify the patient from metabolic surgery
Pregnancy, the intention of becoming pregnant, or not using adequate contraceptive measures
Breastfeeding
Diagnosis of malignancy within the preceding 3 years (except squamous cell and basal cell cancer of the skin)
Anemia defined as hemoglobin less than 9 g/dL
On therapeutic dose of anticoagulants such as warfarin or direct oral anticoagulants (DOACs)
Known history of clotting disorders, including pulmonary embolus and deep vein thrombosis
Clinical judgment that life expectancy is less than 3 years
Use of investigational therapy within 3 months prior to signing the consent
History of pancreatic carcinoma
Acute pancreatitis \< 180 days before screening
History or presence of chronic pancreatitis
Presence of concerning thyroid nodule
Uncontrolled thyroid disease: thyroid stimulating hormone (TSH) \> 6.0 mIU/L or \< 0.1 mIU/L before the first study visit
- Patients receiving treatment for hypothyroidism can be included if their thyroid hormone replacement dose has been stable for at least 3 months.
- Patients whose TSH is outside the rang but they have normal levels of thyroid hormones can be included.
A personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
Evidence or history of ascites or spontaneous bacterial peritonitis that require(d) treatment
- Trace ascites identified only by an abdominal imaging without other evidence of clinically significant portal hypertension and esophageal varices is not an exclusion criterion.
Evidence or history of hepatic encephalopathy
Evidence or history of variceal bleeding
Evidence or history of portosplenic vein thrombosis
Current or history of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to the first study visit.
- Defined as more than 14 units/week for females (\>1 drink per day) and more than 21 units/week for males (\>2 drinks per day) on average, where one unit of alcohol is equivalent to a 12-oz beer, 4-ounce glass of wine, or 1-ounce shot of hard liquor.
Treatment with medications (for more than 14 consecutive days) with known effect on liver steatosis (e.g., treatment with systemic corticosteroids \[oral or intravenous\], methotrexate, tamoxifen, valproic acid, amiodarone, or tetracycline) in the 3 months prior to the first study visit (or historical liver biopsy).
ALT or AST or Alkaline phosphatase \>200 U/L
Recurrent major hypoglycemia or hypoglycemic unawareness
Inability to safely obtain a liver biopsy
Any condition or major illness that, in the investigator's judgment, places the subject at undue risk by participating in the study
Unable to understand the risks, benefits, and compliance requirements of study
Lack capacity to give informed consent
Plans to move outside the primary location of study (country) within the next 24 months
Known or suspected allergy to semaglutide, tirzepatide, liraglutide, excipients, or related products
Previous participation in this trial and got randomized to one of the study groups but did not proceed.
Hospitalization due to COVID-19 within 2 months prior to screening.
Platelet count \<80,000
International Normalized Ratio (INR) \>1.7
Child-Pugh score B or C
MELD score ≥15
Upper endoscopy showing gastroesophageal varices
Upper endoscopy showing more than mild portal hypertensive gastropathy
Liver vascular ultrasound (duplex ultrasonography) showing significant portal hypertension characterized by dilated portal vein (\>13 mm), biphasic or reverse flow in the portal vein, enlarged paraumbilical veins, splenorenal collaterals, or dilated left and short gastric veins.
- Note: Negative findings on upper endoscopy and liver duplex ultrasound (done within one year of the first study visit for both tests) are necessary to establish eligibility for the FLAMES.
- Ruling out clinically significant portal hypertension is particularly important in patients with a liver stiffness ≥20 kPa or with a platelet count \<150,000 per μL or with a (historical) liver biopsy showing cirrhosis.
- A subset of patients without having upper endoscopy and liver duplex ultrasound can be eligible for enrollment if their:
- liver stiffness (by transient elastography using FibroScan®) is between 12 and 15 kPa and their platelet count is \>150,000 per μL, or
- a (historical) liver biopsy showing absence of cirrhosis, or
- a (historical) HVPG \< 5 mmHg
Cross-sectional abdominal imaging (if available historically) indicating presence of large portosystemic collaterals or ascites
- Splenomegaly alone (in the absence of other radiological and laboratory findings) is not considered to be a sign of clinically significant portal hypertension and is not an exclusion criterion.
HVPG ≥ 12 mmHg (if available historically or if measured at the time of de novo liver biopsy)
Liver biopsy characteristics:
- F0 in de novo biopsy; Enrollment cap of 20% for F1 in de novo biopsy.
- F0 and F1 in historical liver biopsy
- Absence of all three components of MASH (steatosis, hepatocyte ballooning, and lobular inﬂammation) in patients with F1, F2, and F3
- Absence of steatosis (\<5%) in patients with F4
- Diagnosis other than MASH

Életkor a regiszterben: 18 év – 75 év · Nem: nők és férfiak · Egészséges önkénteseket is fogad

A teljes feltétellista: ClinicalTrials.gov

Helyszínek (22)

Helyszínek a regiszter sorrendjében. Ha a profilodba mented a városodat, távolság szerint rendeződnek.

Helyszín	Város	Ország	Helyszín állapota
Hospital Alemão Oswaldo Cruz Ennek a helyszínnek vagy a koordinátora? Erősítsd meg az állapotát	São Paulo	Brazília	Toboroz
McGill University Ennek a helyszínnek vagy a koordinátora? Erősítsd meg az állapotát	Montreal	Kanada	Toborzás még nem indult
Clarunis Universitäres Ennek a helyszínnek vagy a koordinátora? Erősítsd meg az állapotát	Basel	Svájc	Toborzás még nem indult
Hôpitaux universitaires de Genève Ennek a helyszínnek vagy a koordinátora? Erősítsd meg az állapotát	Geneva	Svájc	Toborzás még nem indult
Hospital Clinic Barcelona Ennek a helyszínnek vagy a koordinátora? Erősítsd meg az állapotát	Barcelona	Spanyolország	Toborzás még nem indult
Turku University Hospital Ennek a helyszínnek vagy a koordinátora? Erősítsd meg az állapotát	Turku	Finnország	Toborzás még nem indult
Nuffield Health Bristol Hospital Ennek a helyszínnek vagy a koordinátora? Erősítsd meg az állapotát	Bristol	Egyesült Királyság	Toborzás még nem indult
Queen Mary University Ennek a helyszínnek vagy a koordinátora? Erősítsd meg az állapotát	London	Egyesült Királyság	Toborzás még nem indult
King's College Hospital Ennek a helyszínnek vagy a koordinátora? Erősítsd meg az állapotát	London	Egyesült Királyság	Toborzás még nem indult
University College Dublin Ennek a helyszínnek vagy a koordinátora? Erősítsd meg az állapotát	Dublin	Írország	Toborzás még nem indult
Sri Aurobindo Institute of Medical Sciences Ennek a helyszínnek vagy a koordinátora? Erősítsd meg az állapotát	Indore	India	Toborzás még nem indult
The Digestive Health Institute Ennek a helyszínnek vagy a koordinátora? Erősítsd meg az állapotát	Mumbai	India	Toborzás még nem indult
Università Cattolica del Sacro Cuore Ennek a helyszínnek vagy a koordinátora? Erősítsd meg az állapotát	Milan	Olaszország	Toborzás még nem indult
Sapienza Università di Roma Ennek a helyszínnek vagy a koordinátora? Erősítsd meg az állapotát	Roma	Olaszország	Toborzás még nem indult
Kuwait University Ennek a helyszínnek vagy a koordinátora? Erősítsd meg az állapotát	Kuwait City	Kuvait	Toborzás még nem indult
Instituto Nacional de Ciencias Médicas y Nutrición Salvador Ennek a helyszínnek vagy a koordinátora? Erősítsd meg az állapotát	Mexico City	Mexikó	Toborzás még nem indult
Linköping University Ennek a helyszínnek vagy a koordinátora? Erősítsd meg az állapotát	Linköping	Svédország	Toborzás még nem indult
Örebro University Ennek a helyszínnek vagy a koordinátora? Erősítsd meg az állapotát	Örebro	Svédország	Toborzás még nem indult
Cleveland Clinic Ennek a helyszínnek vagy a koordinátora? Erősítsd meg az állapotát	Cleveland	Egyesült Államok	Toboroz
Indiana University Ennek a helyszínnek vagy a koordinátora? Erősítsd meg az állapotát	Indianapolis	Egyesült Államok	Toborzás még nem indult
Banner Health Center Ennek a helyszínnek vagy a koordinátora? Erősítsd meg az állapotát	Phoenix	Egyesült Államok	Toborzás még nem indult
Mayo Clinic Ennek a helyszínnek vagy a koordinátora? Erősítsd meg az állapotát	Rochester	Egyesült Államok	Toborzás még nem indult

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