Bariatric Surgery Versus Non-alcoholic Steato-hepatitis

Not Applicable

Completed

• Conditions: Non Alcoholic Steatohepatitis
• Interventions: Procedure: RYGB; Procedure: SG; Other: Intensive Lifestyle Modification

• Registration Number: NCT03524365
• Lead Sponsor: Catholic University of the Sacred Heart

Brief Summary

Bariatric-metabolic surgery is effective in treating the cluster of conditions forming the metabolic syndrome, strictly associated with NAFLD and NASH. Recently, we and other authors have shown also in the long term (up 5 years) with randomized-controlled trials (RCTs) that bariatric-metabolic surgery allows remission of type 2 diabetes and obesity reduction, which are the two major pathogenetic factors of NASH development, with maintenance of weight loss.

Few small and mainly retrospective studies have shown that bariatric surgery is effective in improving NASH histologic picture in obese subjects.

The aim of our proposal is to conduct a 3 arm single centre, superiority, RCT comparing Roux-en-Y Gastric Bypass (RYGB) with Sleeve Gastrectomy (SG) and with Intensive Lifestyle Modifications (ILM) for the treatment of Non-Alcoholic Steato-Hepatitis.

Detailed Description

This is a Randomized Controlled multicentre Trial involving the Catholic University (Professor Geltrude Mingrone as PI and Professor Marco Raffaelli as co-PI)

The research question in PICOT format (P) - Population: Adults 25 to 70 years of age and BMI ≥ 30 and ≤55 kg/m2 with histological diagnosis of NASH.

(I) - Intervention: Roux-en-Y Gastric Bypass or Sleeve Gastrectomy, both plus lifestyle counseling.

(C) - Comparison: Intensive Lifestyle Modifications. (O) - Outcome: the histological resolution of NASH without worsening of fibrosis at 1 year after the interventions.

(T) - Time: One year after the intervention started.

1.3.3.2 Research Goals

* The primary aim of our study is to assess the effects of bariatric-metabolic surgery or ILM on NASH at 1 year after the interventions.

* Secondary aims are to assess the safety of bariatric surgery and the improvement of at least 1 stage of liver fibrosis without worsening of NASH, insulin sensitivity , T2DM, and lipoprotein profile changes.

The liver biopsy will be performed at baseline and at 1 year follow-up. Another liver biopsy will be performed at 3 and 5 years follow-up.

Study Timeline

• Study First Submitted: 2018-04-21
• Study First Submitted QC: 2018-05-02
• Study First Posted: 2018-05-14
• Study Start: 2018-12-06
• Primary Completion: 2022-07-20
• Study Completion: 2022-07-20
• Status Verified: 2023-02
• Last Update Submitted: 2023-02-17
• Last Update Posted: 2023-02-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 288

Inclusion Criteria

• Subjects with NASH documented by liver biopsy and no evidence of another form of liver disease with a BMI ≥ 30 and ≤55 kg/m2.

Subjects with normal liver who underwent laparoscopic elective cholecystectomy, but otherwise in healthy conditions, will be used as controls for the discovery of non-invasive biomarkers.

Exclusion Criteria

• Coronary event or procedure (myocardial infarction, unstable angina, coronary artery bypass, surgery or coronary angioplasty) in the previous 6 months; Liver cirrhosis; End stage renal failure; Participation in any other concurrent therapeutic clinical trial; Any other life-threatening, non-cardiac disease; Pregnancy; Inability to give informed consent; Substantial alcohol consumption (>20 g/day for women or >30 g/day for men); Wilson's disease;hepatitis B virus, hepatitis C virus (negative Hepatitis C RNA since more than 3 years will be considered eligible), autoimmune hepatitis, primary biliary cholangitis, haemochromatosis and α-1-antitrypsin deficiency; Lipodystrophy; Parenteral nutrition; Abetalipoproteinemia; Interfering medications (e.g., amiodarone, methotrexate, tamoxifen, corticosteroids).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
RYGB plus LM counselling	RYGB	96 subjects with NASH
SG plus LM counselling	SG	96 subjects with NASH
ILM	Intensive Lifestyle Modification	96 subjects with NASH

Primary Outcome Measures

Name	Time	Method
histological resolution of NASH without worsening of fibrosis at 1 year after the interventions	1 year	Histological diagnosis of NASH is established according to widely accepted criteria, using the NAFLD activity score (NAS) algorithm proposed by the NASH Clinical Research Network (CRN). These criteria include presence of steatosis in \>5% of hepatocytes, hepatocellular ballooning and lobular inflammatory infiltrates. The presence and stages of fibrosis will be also assessed using the NASH-CRN system: stage 0 =no fibrosis; stage 1 =centrilobular pericellular fibrosis; stage 2 =centrilobular and periportal fibrosis; stage 3 =bridging fibrosis; and stage 4 =cirrhosis.

Secondary Outcome Measures

Name	Time	Method
Changes in insulin sensitivity	1 year	HOMA IR or oral glucose minimal model
Changes in food intake	1 year	food intake diary
Adverse health events including the need for re-operation	1 year	adverse events include early operation complications
Changes in glycemic control (only in diabetic patients)	1 year	diabetes remission or improvement of glycemic control (glycated hemoglobin HbA1c)
Improvement of at least 1 point of histological liver fibrosis without worsening of NASH	1 year	liver fibrosis will be examined in liver biopsies
Changes in physical activity	1 year	Physical activity questionnaire
Changes in body composition: Fat-Free Mass (FFM), Fat Mass (FM).	1 year	FFM and FM will be assessed by DEXA

Trial Locations

Locations (3)

San Camillo; 🇮🇹 Roma, Italy

University of Rome Sapienza; 🇮🇹 Roma, Italy

Catholic University School of Medicine; 🇮🇹 Rome, Italy