Prospective Multicentric, Open Label, Randomized Clinical Trial of Superiority, With Two Arms, Comparing Bariatric Surgery to the Recommended Medical Treatment for NASH

University Hospital, Lille1 个研究点分布在 1 个国家目标入组 100 人2018年6月20日

适应症Surgery Obesity NASH - Nonalcoholic Steatohepatitis Cirrhosis

干预措施Bariatric surgery Lifestyle therapy

概览

阶段: 不适用
干预措施: Bariatric surgery
疾病 / 适应症: Surgery
发起方: University Hospital, Lille
入组人数: 100
试验地点: 1
主要终点: Rate of disappearance of NASH without worsening of fibrosis grade
状态: 招募中
最后更新: 10天前

概览研究者入排标准研究组 & 干预措施结局指标研究点相似试验

概览

简要总结

The aim of the study is to demonstrate the superiority of bariatric surgery on the disappearance of NASH without worsening of fibrosis in comparison to medical standard treatment in obese patients (35 kg/m² > BMI ≥ 30 kg/m²) with NASH complicated of advanced fibrosis (F3 and F4 fibrosis grade according to Brunt score).

注册库

clinicaltrials.gov

开始日期

2018年6月20日

结束日期

2028年6月20日

最后更新

10天前

研究类型

Interventional

研究设计

Parallel

性别

All

研究者

发起方

University Hospital, Lille

责任方

Sponsor

入排标准

入选标准

•Provide written informed consent and agree to comply to the study protocol prior to enrolment.
•BMI and Brunt Fibriosis score:
•For F3 fibrosis patients: 35\>BMI≥ 30kg/m² ; Fibroscan ≥ 9kPa or FibrometreVM ≥0.526 predicting a F3 fibrosis score grade within 1 month before inclusion or F3 fibrosis score grade diagnosed by hepatic biopsy performed before inclusion.
•For F4 fibrosis patients: 50\>BMI≥ 30kg/m² ; Fibroscan ≥ 15kPa predicting a F4 fibrosis score grade within 1 month before inclusion or F4 fibrosis score grade diagnosed by hepatic biopsy performed before inclusion.
•Fibroscan ≥ 9kPa or FibrometreVM ≥0.526 predicting a F3 or F4 fibrosis score grade within 1 month before inclusion Or F3 or F4 fibrosis score grade diagnosed by hepatic biopsy performed before inclusion.
•Patient should agree to have one liver biopsy during the screening period (before randomization, the randomization will be permitted after at least a second reading performed by pathologist of CHRU Lille to confirm the histological diagnosis of NASH with advanced fibrosis (F3-F4)) for the diagnosis purpose (if no histological biopsy within 1 month before inclusion is available) and one at the end of the treatment period for assessment of the treatment effects.
•For patients with cirrhosis, patients must fulfil all the following criteria: Platelets \> 125 000, PT \> 80 %, Albumin \> 35 g/L, MELD score at inclusion \< 9, CPT score \< 6, No history of previous decompensation, No oesophageal varices (endoscopy), No vascular shunt, ASA score ≤ III, Alcohol consumption lower than 20g/day for women and 30g/day for men.
•For hypertensive patients, hypertension must be controlled by stable dose of anti-hypertensive medication for at least 2 months prior to screening (and the stable dose can be maintained throughout the study).
•Female participating in the study must be either of non-child bearing (surgically sterilized at 6 month prior to screening or postmenopausal) or using an efficient contraception: hormonal contraception (including patch, contraceptive ring etc) intra-uterine device or other mechanical contraception
•Patient agrees to come to the study visits within the protocol-specified delay

排除标准

•Previous history of bariatric surgery (except gastric ring removed for more than 3 years).
•Decompensated cirrhosis (MELD\> 7 CPT score\> 5, previous history of decompensation (encephalopathy, ascites, jaundice, varicose vein rupture)
•Hepatocellular carcinoma
•Platelets \<125 000; TP \<80%; bilirubin \<20 mmol / l; albumin \<35 g / L.
•Other liver disease: alcohol consumption exceeding 20 g / day for women and 30g / day in men, HBV, HCV, CBP, CSP, autoimmune hepatitis, hemochromatosis, Wilson's disease, alpha-1 antitrypsin.
•Being processed Cancer (chemotherapy, radiotherapy or hormone therapy)
•HIV positive patients
•Patients who had an acute cardiovascular episode, coronary Heart Disease (Angina pectoris, myocardial infarction, revascularization procedure), stroke or TIA (Transient Ischemic Attack) within the 6 months prior to screening Recent cardiovascular events (stroke, myocardial infarcts, etc…) in the past 6 months.
•Severe chronic respiratory disease.
•Severe chronic cardiac insufficiency (grade III and IV of NYHA classification).

研究组 & 干预措施

Bariatric surgery

Two different types of bariatric surgery can be proposed: laparoscopic Roux-en-Y Gastric Bypass or a Laparoscopic sleeve gastrectomy. Decision of the surgery type will be made according to surgical expertise, habits of investigation centers and the patient's desire. All patients receive nutritional support and therapeutic education adapted to recommendations bariatric surgery care.

干预措施: Bariatric surgery

Lifestyle therapy

The group will received the medical standard treatment defined as lifestyle therapy combining diet with increased physical activity (standard treatment, control) (figure 1, design of study).

干预措施: Lifestyle therapy

结局指标

主要结局

Rate of disappearance of NASH without worsening of fibrosis grade

时间窗: at 60 weeks after randomization

Diagnosis of NASH on the liver biopsy

次要结局

Change in Alanine transaminase (ALT)(at 60 weeks after randomization)
Percentage of patients achieving at least a 2 point improvement in the NAS (≥2 points) without worsening of fibrosis grade(at 60 weeks after randomization)
Change in total bilirubin(at 60 weeks after randomization)
Change in the Brunt fibrosis score,(at 60 weeks after randomization)
Percentage of patient achieving 5 and 10% of weight loss from randomization to end of treatment.(at 60 weeks after randomization)
Change in INR (International Normalized Ratio)(at 60 weeks after randomization)
Change in the SF-36 quality of life score.(at 60 weeks after randomization)
Change in total cholesterol.(at 60 weeks after randomization)
Change in the Metavir score(at 60 weeks after randomization)
Change in Albumin(at 60 weeks after randomization)
Change in Fasting glucose(at 60 weeks after randomization)
Change in Glycated haemoglobin(at 60 weeks after randomization)
Change in the NAS (Nafld Activity Score) score(at 60 weeks after randomization)
Change in the fibrosis area(at 60 weeks after randomization)
Percentage of patients with at least one of the following complications(through study completion)
Change in ALP(at 60 weeks after randomization)
Change in metabolic profile assessed by HOMA score(at 60 weeks after randomization)
Change in HDL cholesterol(at 60 weeks after randomization)
Change in serum triglycerides(at 60 weeks after randomization)
Change in LDL cholesterol(at 60 weeks after randomization)
Change in aspartate transaminase (AST)(at 60 weeks after randomization)
Change in GGT(at 60 weeks after randomization)