Bariatric Surgery Versus Non-alcoholic Steato-hepatitis (BRAVES)

Catholic University of the Sacred Heart

Status: Completed

Conditions: Non Alcoholic Steatohepatitis

Treatments: Procedure: SG; Other: Intensive Lifestyle Modification; Procedure: RYGB

Study type: Interventional

Funder types: Other

Identifiers

NCT03524365

20182004

Details and patient eligibility

About

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.

Full 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.

Enrollment: 288 patients

Sex: All

Ages: 25 to 70 years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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288 participants in 3 patient groups

RYGB plus LM counselling

Active Comparator group

Description:

96 subjects with NASH

Treatment:

Procedure: RYGB

SG plus LM counselling

Active Comparator group

Description:

96 subjects with NASH

Treatment:

Procedure: SG

ILM

Sham Comparator group

Description:

96 subjects with NASH

Treatment:

Other: Intensive Lifestyle Modification