STudy to Evaluate the Efficacy and Safety of Endoscopic Sleeve Gastroplasty (ESG) Versus LAparoscopic Sleeve Gastrectomy (LSG) in Obese Subjects With Non-Alcoholic SteatoHepatitis (NASH)
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Proportion of subjects undergoing ESG relative to LSG achieving resolution of NASH without worsening of fibrosis
研究概览
简要总结
The primary objectives of this study are to evaluate the effect of ESG with OverStitch® system (Apollo Endosurgery, Austin, TX, USA) compared to LSG on 1) histological improvement in NASH; 2) all-cause mortality and liver-related outcomes In obese subjects with non-alcoholic steatohepatitis (NASH).
Condition or disease: Non-alcoholic steatohepatitis (NASH) with or without fibrosis Intervention/treatment: ESG with OverStitch® system vs LSG
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects aged between 18 and 60 years (inclusive) at first screening visit.
- •Must provide signed written informed consent and agree to comply with the study protocol.
- •BMI between 35 and 45 kg/m2 with or without metabolic risk factors (type 2 diabetes, arterial hypertension, dyslipidaemia), and BMI between 30 and 34,9 kg/m2 with type 2 diabetes.
- •Histological confirmation of steatohepatitis in a diagnostic liver biopsy (biopsy obtained in the 6 months prior to randomization or during the selection period) with at least a score of 1 in each component of the NAS score (steatosis with a score of 0 to 3, degeneration by ballooning with a score of 0 to 2 and lobular inflammation with a score of 0 to 3) and:
- •NAS score ≥ 4
- •fibrosis < 4 according to the staging system of CRN fibrosis on NASH
- •For patients with fibrosis ≤ 1, must be associated at least one of the following conditions: metabolic syndrome (NCEP ATP III definition), type 2 diabetes, HOMA-IR >6
- •Absence of other well documented causes of chronic liver disease (alcoholic liver disease, viral hepatitis, cholestasis, autoimmune hepatitis, Wilson's disease, hemochromatosis, alpha 1 antitrypsin deficiency)
- •Patients agree to have 1 liver biopsy after 96 weeks after intervention
排除标准
- •Known heart failure (Grade I to IV of the classification of the New York Heart Association).
- •History of efficient bariatric surgery within 10 years prior to Screening.
- •Patients with a history of clinically significant acute cardiac event in the 6 months prior to selection, such as: acute cardiovascular event, cerebrovascular accident, transient ischemic attack, or coronary heart disease (angina pectoris, myocardial infarction, revascularization procedures).
- •Weight loss of more than 5% in the 6 months prior to randomization.
- •Recent or current background of significant consumption of alcoholic beverages (<5 years). In the case of men, significant consumption is usually defined as more than 30 g of pure alcohol per day. In the case of women, it is usually defined as more than 20 g of pure alcohol per day.
- •Liver cirrhosis.
- •Non-cirrhotic portal hypertension.
- •Esophagogastric varices.
- •Hepatocellular carcinoma
- •Portal thrombosis.
- •Refusal to give informed consent.
- •Any medical condition that could reduce life expectancy to less than 2 years, including known cancers.
- •Signs of any other unstable or clinically significant immunological, endocrine, hematological, gastrointestinal, neurological, neoplastic or psychiatric disease without treatment.
- •Instability or mental incompetence, so that the validity of the informed consent or the ability to comply with the study are uncertain.
- •Antibodies positive for the human immunodeficiency virus.
- •Descompensated liver disease with the following hematologic and biochemical criteria:
- •Aspartate aminotransferase (AST) and / or ALT> 10 x upper limit of normal (ULN)
- •Total bilirubin> 25 μmol / l (1.5 mg / dl)
- •Standardized international index> 1.4
- •Platelet count <100 000 / mm3
- •Serum creatinine levels> 135 μmol / l (> 1.53 mg / dl) in men and> 110 μmol / l (> 1.24 mg / dl) in women.
- •Significant renal disease, including nephritic syndrome, chronic kidney disease (patients with markers of hepatic injury or estimated glomerular filtration rate [eGFR] of less than 60 ml / min / 1.73 m2). If an abnormal value is obtained at the first screening visit, the eGFR measurement may be repeated before randomization within the following time frame: minimum 4 weeks after the initial test and maximum 2 weeks before the expected randomization. An abnormal repeated eGFR (less than 60 ml / min / 1.73 m2) leads to exclusion from the study.
结局指标
主要结局
Proportion of subjects undergoing ESG relative to LSG achieving resolution of NASH without worsening of fibrosis
时间窗: Measurement at 96 weeks
To evaluate the effect of ESG compared to LSG on liver histology in obese subjects with NASH with or without fibrosis by assessing the following endpoint: The proportion of subjects undergoing ESG relative to LSG achieving NASH resolution without worsening of fibrosis. NASH resolution is defined as the disappearance of ballooning and the disappearance or persistence of minimal lobular inflammation (grade 0 or 1) The worsening of fibrosis is defined as the progression of at least one stage.
Proportion of subjects undergoing ESG relative to LSG with cardiovascular and liver-related death events
时间窗: Measurement at 96 weeks
To evaluate the effect of ESG compared to LSG on liver histology in obese subjects with NASH with fibrosis by assessing the following endpoint: The proportion of subjects undergoing ESG relative to LSG achieving improvement of liver fibrosis of at least one stage.
次要结局
- Proportion of subjects undergoing ESG relative to LSG achieving improvement in liver histology according to the NASH-CRN scoring(Measurement at 96 weeks)
- Changes in the liver enzymes(Measurement at 96 weeks)
- Changes in body weight(Measurement at 96 weeks)
- Changes in serum expression of incretins(Measurement at 96 weeks)
- Changes in lipid parameter(Measurement at 96 weeks)
- Changes in mineral metabolism parameters.(Measurement at 96 weeks)
- Changes in gut microbiota(Measurement at 96 weeks)
- Incidence of adverse events(Measurement at 96 weeks)
- Changes in noninvasive markers of fibrosis and steatosis(Measurement at 96 weeks)
- Changes in inflammatory markers(Measurement at 96 weeks)
- Changes in glucose homeostasis markers and insulin resistance(Measurement at 96 weeks)
研究者
UECV
Dr. Javier Crespo
Instituto de Investigación Marqués de Valdecilla