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

NCT ID: NCT03472157

Last Updated: 2023-01-27

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-06-20
• Study Completion Date: 2026-03-31

Brief Summary

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).

Conditions

Surgery; Obesity; NASH - Nonalcoholic Steatohepatitis; Cirrhosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Bariatric surgery

Intervention Type: PROCEDURE

Two different types of bariatric surgery can be proposed: laparoscopic Roux-en-Y Gastric Bypass or a Laparoscopic sleeve gastrectomy

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).

Group Type: ACTIVE_COMPARATOR

Lifestyle therapy

Intervention Type: OTHER

Lifestyle habits (caloric intake and exercise) + pedometer

Interventions

Lifestyle therapy

Lifestyle habits (caloric intake and exercise) + pedometer

Intervention Type: OTHER

Bariatric surgery

Two different types of bariatric surgery can be proposed: laparoscopic Roux-en-Y Gastric Bypass or a Laparoscopic sleeve gastrectomy

Intervention Type: PROCEDURE

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ministry of Health, France

OTHER_GOV

Sponsor Role: collaborator

University Hospital, Lille

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Philippe Mathurin, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Lille

Locations

Hôpital Claude Huriez, CHRU

Lille, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Philippe Mathurin, MD,PhD

Role: CONTACT

philippe.mathurin@chru-lille.fr

3 20 44 53 21 ext. +33

Guillaume Lassailly, MD

Role: CONTACT

guillaume.lassailly@chru-lille.fr

3 20 44 53 21 ext. +33

Other Identifiers

2017-A01575-48

Identifier Type: OTHER

Identifier Source: secondary_id

2016_78

Identifier Type: -

Identifier Source: org_study_id