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

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ClinicalTrials.gov Identifier: NCT03472157
Recruitment Status : Recruiting
First Posted : March 21, 2018
Last Update Posted : September 12, 2018
Sponsor:
Collaborator:
Ministry of Health, France
Information provided by (Responsible Party):
University Hospital, Lille

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).

Condition or disease Intervention/treatment Phase
Surgery Obesity NASH - Nonalcoholic Steatohepatitis Cirrhosis Other: Lifestyle therapy Procedure: Bariatric surgery Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Prospective Multicentric, Open Label, Randomized Clinical Trial of Superiority, With Two Arms, Comparing Bariatric Surgery to the Recommended Medical Treatment for NASH
Actual Study Start Date : June 20, 2018
Estimated Primary Completion Date : March 2023
Estimated Study Completion Date : March 2023


Arm Intervention/treatment
Experimental: 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.

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

Active Comparator: 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).
Other: Lifestyle therapy
Lifestyle habits (caloric intake and exercise) + pedometer




Primary Outcome Measures :
  1. Rate of disappearance of NASH without worsening of fibrosis grade [ Time Frame: at 60 weeks after randomization ]
    Diagnosis of NASH on the liver biopsy


Secondary Outcome Measures :
  1. Change in the NAS (Nafld Activity Score) score [ Time Frame: at 60 weeks after randomization ]
    NAS is a histological score established on the liver biopsy. The NAS ranges form 0 to 8. 8 is associated with the highest severity.

  2. 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 ]
    NAS established on the liver biopsy

  3. Change in the Brunt fibrosis score, [ Time Frame: at 60 weeks after randomization ]
    Brunt fibrosis is a histological score ranges from 0 to 4. The Brunt fibrosis score is established on the liver biopsy. It is the recommended score for the evaluation of fibrosis in NASH and NAFLD. On the scale, "0" is an absence of fibrosis, whereas "4" matches with cirrhosis.

  4. Change in the Metavir score [ Time Frame: at 60 weeks after randomization ]
    METAVIR fibrosis score is established on the liver biopsy. METAVIR fibrosis is a histological score ranges from 0 to 4. This score is more discriminant than the Brunt score for the severe form of fibrosis that are included in this study.On the scale, "0" is an absence of fibrosis, whereas "4" matches with cirrhosis.

  5. Change in the fibrosis area [ Time Frame: at 60 weeks after randomization ]
    computerized morphometry analysis of fibrosis area

  6. Change in the SF-36 quality of life score. [ Time Frame: at 60 weeks after randomization ]
    SF-36 quality of life score

  7. Percentage of patients with at least one of the following complications [ Time Frame: through study completion ]
    complications: infection, thromboembolic complications, haemorrhage, rhabdomyolysis, hepatic decompensation and death

  8. Percentage of patient achieving 5 and 10% of weight loss from randomization to end of treatment. [ Time Frame: at 60 weeks after randomization ]
    Weight

  9. Change in aspartate transaminase (AST) [ Time Frame: at 60 weeks after randomization ]
    AST is a liver enzyme, used for the biological liver test evaluation.

  10. Change in Alanine transaminase (ALT) [ Time Frame: at 60 weeks after randomization ]
    ALT is a liver enzyme, used for the biological liver test evaluation.

  11. Change in total bilirubin [ Time Frame: at 60 weeks after randomization ]
    Total bilirubin is a liver enzyme, used for the biological liver test evaluation.

  12. Change in GGT [ Time Frame: at 60 weeks after randomization ]
    GGT (gamma glutamyl transferase) is a liver enzyme, used for the biological liver test evaluation. .

  13. Change in ALP [ Time Frame: at 60 weeks after randomization ]
    Alkalin Phosphatase is a liver enzyme, used for the biological liver test evaluation.

  14. Change in INR (International Normalized Ratio) [ Time Frame: at 60 weeks after randomization ]
    INR represents coagulation but also liver hepatocellular function.

  15. Change in Albumin [ Time Frame: at 60 weeks after randomization ]
    Albumin is used a marker of nutrition and hepatocellular function

  16. Change in metabolic profile assessed by HOMA score [ Time Frame: at 60 weeks after randomization ]
    HOMA is a score (scale) evaluating insulin resistance.

  17. Change in Fasting glucose [ Time Frame: at 60 weeks after randomization ]
    fasting glucose is a marker of diabetes and insulin resistance

  18. Change in Glycated haemoglobin [ Time Frame: at 60 weeks after randomization ]
    glycated haemoglobin is a surrogate marker for diabetes management and outcome.

  19. Change in HDL cholesterol [ Time Frame: at 60 weeks after randomization ]
    HDL cholesterol is a biomarker for lipid metabolism and cardiovascular risk

  20. Change in serum triglycerides [ Time Frame: at 60 weeks after randomization ]
    serum triglycerides is a biomarker for lipid metabolism and cardiovascular risk

  21. Change in LDL cholesterol [ Time Frame: at 60 weeks after randomization ]
    LDL cholesterol is a biomarker for lipid metabolism and cardiovascular risk

  22. Change in total cholesterol. [ Time Frame: at 60 weeks after randomization ]
    total cholesterol is a biomarker for lipid metabolism and cardiovascular risk



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Provide written informed consent and agree to comply to the study protocol prior to enrolment.
  • Patients 18 to 65 years of age
  • 30 kg/m² ≤ BMI < 35 kg/m²
  • Fibroscan ≥ 9kPa and 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 (4 months after inclusion) 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 < 8, CPT score < 6, No history of previous decompensation, No oesophageal varices (endoscopy), No vascular shunt, ASA score ≤ III, No alcohol consumption
  • 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:

  • BMI ≥ 35 kg / m2 or < 30 kg/m²
  • Previous history of bariatric surgery.
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03472157


Contacts
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Contact: Philippe Mathurin, MD,PhD 3 20 44 53 21 ext +33 philippe.mathurin@chru-lille.fr
Contact: Guillaume Lassailly, MD 3 20 44 53 21 ext +33 guillaume.lassailly@chru-lille.fr

Locations
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France
Hôpital Claude Huriez, CHRU Recruiting
Lille, France
Principal Investigator: Guillaume Lassailly, MD         
Sponsors and Collaborators
University Hospital, Lille
Ministry of Health, France
Investigators
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Principal Investigator: Philippe Mathurin, MD,PhD University Hospital, Lille

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Responsible Party: University Hospital, Lille
ClinicalTrials.gov Identifier: NCT03472157     History of Changes
Other Study ID Numbers: 2016_78
2017-A01575-48 ( Other Identifier: ID-RCB number, ANSM )
First Posted: March 21, 2018    Key Record Dates
Last Update Posted: September 12, 2018
Last Verified: May 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University Hospital, Lille:
Gastric bypass
Sleeve gastrectomy
Lifestyle therapy
NASH
Advanced fibrosis
Cirrhosis

Additional relevant MeSH terms:
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Fibrosis
Fatty Liver
Non-alcoholic Fatty Liver Disease
Pathologic Processes
Liver Diseases
Digestive System Diseases