A Randomized Controlled Study on the Effects of Roux-en-Y Gastric Bypass Versus Sleeve Gastrectomy or Intensive Lifestyle Modifications on Non Alcoholic Steato-Hepatitis
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Enrollment
- 288
- Locations
- 3
- Primary Endpoint
- histological resolution of NASH without worsening of fibrosis at 1 year after the interventions
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 25 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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/m
- •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).
Arms & Interventions
RYGB plus LM counselling
96 subjects with NASH
Intervention: RYGB (Procedure)
SG plus LM counselling
96 subjects with NASH
Intervention: SG (Procedure)
ILM
96 subjects with NASH
Intervention: Intensive Lifestyle Modification (Other)
Outcomes
Primary Outcomes
histological resolution of NASH without worsening of fibrosis at 1 year after the interventions
Time Frame: 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 Outcomes
- Changes in insulin sensitivity(1 year)
- Changes in food intake(1 year)
- Adverse health events including the need for re-operation(1 year)
- Changes in glycemic control (only in diabetic patients)(1 year)
- Improvement of at least 1 point of histological liver fibrosis without worsening of NASH(1 year)
- Changes in physical activity(1 year)
- Changes in body composition: Fat-Free Mass (FFM), Fat Mass (FM).(1 year)
Investigators
Geltrude Mingrone
Associate Professor of Internal Medicine
Catholic University of the Sacred Heart