Bariatric Surgery Versus Non-alcoholic Steato-hepatitis

NCT03524365 | Completed

• 1 other identifier: 20182004
• Study Type: interventional
• Target: 288
• Locations: 1 country
• Sites: 3

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.

Conditions

Non Alcoholic Steatohepatitis

Outcome Measures

Primary Outcomes (1)

• histological resolution of NASH without worsening of fibrosis at 1 year after the interventions

  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.

  1 year

Secondary Outcomes (7)

• Adverse health events including the need for re-operation

  1 year

• Improvement of at least 1 point of histological liver fibrosis without worsening of NASH

  1 year

• Changes in glycemic control (only in diabetic patients)

  1 year

• Changes in insulin sensitivity

  1 year

• Changes in food intake

  1 year

Study Arms (3)

RYGB plus LM counselling

ACTIVE COMPARATOR

96 subjects with NASH

Procedure: RYGB

SG plus LM counselling

ACTIVE COMPARATOR

96 subjects with NASH

Procedure: SG

ILM

SHAM COMPARATOR

96 subjects with NASH

Other: Intensive Lifestyle Modification

Interventions

RYGB PROCEDURE

Roux-\&-Y Gastric Bypass (RYGB) involves the use of a surgical stapler to create a small and vertically oriented gastric pouch with a volume of 30 ml. The upper pouch is completely divided by the gastric remnant and is anastomosed to the jejunum, 75 cm distally to the Treitz's ligament , through a narrow gastrojejunal anastomosis in a Roux-en-Y fashion. Bowel continuity is restored by an entero-entero anastomosis, between the excluded biliary limb and the alimentary limb, performed at 100 cm from the gastrojejunostomy. Lifestyle modification counselling is provided to each patient.

RYGB plus LM counselling

SG PROCEDURE

The SG is created using a linear stapler with two sequential 4.8/60-mm green load firings for the antrum, followed by two or three sequential 3.5/60-mm blue loads for the remaining gastric corpus and fundus. The stapler is applied alongside a 48-Fr calibrating bougie. The resection line is performed avoiding the ''critical area'' by resecting the fundus 1.5 cm from the angle of His. Staple lines are buttressed with bovine pericardial strips. The resected stomach is grasped at the antral tip by a laparoscopic grasper and retrieved through one of the trocar sites. A methylene blue dye test by a nasogastric tube is routinely performed at the end of the procedure. The residual gastric remnant capacity is 60-80 ml. Drains are not routinely placed, and the nasogastric tube is removed at the end of the procedure. Upper gastrointestinal contrast (Gastrografin) study is performed on the first postoperative day. Lifestyle modification counselling is provided to each patient.

SG plus LM counselling

Intensive Lifestyle Modification OTHER

Resting calorie requirements will be calculated via the Harris Benedict equation (24) and an activity factor, and subjects will be instructed not to change their activity level other than that suggested by physicians during the study. The diet will contain 1/3 kcal less than the calculated energy expenditure and 30% fat of which 10% saturated, 55% lower glycemic index carbohydrates and 15% proteins. The participants will be encouraged to gradually increase their walking to achieve 10,000 steps per day. A moderate intensity physical activity program of 1 hour of aerobic exercise 2-3 hours per week will be recommended to all subjects. Their physical activity will be assessed by IPAQ-SF.

ILM

Eligibility Criteria

• Age: 25 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Catholic University of the Sacred Heart: lead
• University of Roma La Sapienza: collaborator

Study Sites (3)

San Camillo

Roma, Italy

Location

University of Rome Sapienza

Roma, Italy

Location

Catholic University School of Medicine

Rome, 00168, Italy

Location

Related Publications (3)

• Angelini G, Panunzi S, Pompili M, Riccardi L, Garcovich M, Verrastro O, Russo S, Mare T, Luxton J, le Roux CW, Raffaelli M, Mingrone G, Vincent RP. Performance of Noninvasive Tests for Metabolic Dysfunction-Associated Steatohepatitis and Liver Fibrosis Resolution after Bariatric Surgery. Clin Chem. 2025 Mar 3;71(3):406-417. doi: 10.1093/clinchem/hvae208.

  PMID: 39786442 DERIVED

• Verrastro O, Panunzi S, Castagneto-Gissey L, De Gaetano A, Lembo E, Capristo E, Guidone C, Angelini G, Pennestri F, Sessa L, Vecchio FM, Riccardi L, Zocco MA, Boskoski I, Casella-Mariolo JR, Marini P, Pompili M, Casella G, Fiori E, Rubino F, Bornstein SR, Raffaelli M, Mingrone G. Bariatric-metabolic surgery versus lifestyle intervention plus best medical care in non-alcoholic steatohepatitis (BRAVES): a multicentre, open-label, randomised trial. Lancet. 2023 May 27;401(10390):1786-1797. doi: 10.1016/S0140-6736(23)00634-7. Epub 2023 Apr 21.

  PMID: 37088093 DERIVED

• Angelini G, Panunzi S, Castagneto-Gissey L, Pellicano F, De Gaetano A, Pompili M, Riccardi L, Garcovich M, Raffaelli M, Ciccoritti L, Verrastro O, Russo MF, Vecchio FM, Casella G, Casella-Mariolo J, Papa L, Marini PL, Rubino F, le Roux CW, Bornstein S, Mingrone G. Accurate liquid biopsy for the diagnosis of non-alcoholic steatohepatitis and liver fibrosis. Gut. 2023 Feb;72(2):392-403. doi: 10.1136/gutjnl-2022-327498. Epub 2022 Jul 12.

  PMID: 35820779 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Study Officials

• Geltrude Mingrone, MD PhD

  Catholic University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Internal Medicine

Study Record Dates

• First Submitted: April 21, 2018
• First Posted: May 14, 2018
• Study Start: December 6, 2018
• Primary Completion: July 20, 2022
• Study Completion: July 20, 2022
• Last Updated: February 21, 2023

Record last verified: 2023-02

Locations

IT (3)