A Randomized Controlled Study Evaluating Bariatric Surgery as a Treatment for Severe NASH With Advanced Liver Fibrosis in Non-severe Obese Patients

Official title

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

Overview

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).

Interventions

• Other Lifestyle therapy
  Lifestyle habits (caloric intake and exercise) + pedometer
• Procedure Bariatric surgery
  Two different types of bariatric surgery can be proposed: laparoscopic Roux-en-Y Gastric Bypass or a Laparoscopic sleeve gastrectomy

Primary outcome measures

• Rate of disappearance of NASH without worsening of fibrosis grade [Time frame: at 60 weeks after randomization]

Secondary outcome measures (12)

• Change in the NAS (Nafld Activity Score) score [Time frame: 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 [Time frame: at 60 weeks after randomization]
• Change in the Brunt fibrosis score, [Time frame: at 60 weeks after randomization]
• Change in the Metavir score [Time frame: at 60 weeks after randomization]
• Change in the fibrosis area [Time frame: at 60 weeks after randomization]
• Change in the SF-36 quality of life score. [Time frame: at 60 weeks after randomization]
• Percentage of patients with at least one of the following complications [Time frame: through study completion]
• Percentage of patient achieving 5 and 10% of weight loss from randomization to end of treatment. [Time frame: at 60 weeks after randomization]
• Change in aspartate transaminase (AST) [Time frame: at 60 weeks after randomization]
• Change in Alanine transaminase (ALT) [Time frame: at 60 weeks after randomization]
• Change in total bilirubin [Time frame: at 60 weeks after randomization]
• Change in GGT [Time frame: at 60 weeks after randomization]

Eligibility criteria

Inclusion criteria

• 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

Exclusion criteria

• 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).
• Pregnant or breastfeeding women.
• Simultaneous enrollment in another clinical trial.
• Drug abuse within the past year.
• Patient with contra-indication for bariatric surgery
• Gastic Banding, Biliopancreatic diversion and all the new bariatric surgery techniques are forbidden because the study design allow only the laparoscopic sleeve gastrectomy or laparoscopic Roux-en-Y gastric Bypaass.
• History of cancer, except:

• Patients considered in remission for at least 5 years after onset of treatment.
• Patients Treated and believed to be cured basal or squamous cell carcinoma of the skin or resected carcinoma of the cervix

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

France · 1 center

• Hôpital Claude Huriez, CHRU — Lille

Identifiers

NCT: NCT03472157 · 2016_78 · 2017-A01575-48

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗