Fibrosis Reduction in Non Alcoholic Steatohepatitis

NCT05798702 | Active Not Recruiting

• 1 other identifier: 4103
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Non-Alcoholic Steatohepatitis (NASH) represents one of the stages of Non-Alcoholic Fatty Liver Disease (NAFLD) with a very high risk to evolve in cirrhosis and hepato-carcinoma. Currently, the only diagnostic method is a liver biopsy that remains the gold standard for characterizing liver histologic alterations and fibrosis stages. There is no specific treatment for NASH, in fact no drugs are currently licensed specifically for treating this disease. Aim: Our aim is to conduct a non-inferiority, randomized-controlled trial (RCT) comparing Roux-en-Y Gastric bypass (RYGB) with an intensive lifestyle modification plan (Very low-calorie diet, VLCD) for the reduction of advanced stages of fibrosis in subjects with obesity and NASH after 25% weight loss.

Conditions

NASH With Fibrosis; Weight Loss; Bariatric Surgery Candidate

Outcome Measures

Primary Outcomes (1)

• histological reduction of fibrosis

  The primary outcome is the rate of histological reduction of 2 points of fibrosis after 25% weight loss following either metabolic surgery or dieting

  2 years

Secondary Outcomes (5)

• Liver histology

  2 years

• Liver Markers

  2 years

• Non-alcoholic Fatty Liver Disease Fibrosis score

  2 years

• Fibrosis-4 (FIB-4) Index

  2 years

• Fibroscan

  2 years

Study Arms (2)

intensive lifestyle modifications

ACTIVE COMPARATOR

VLCD 800-850 Kcal/day

Dietary Supplement: intensive life style modification

Roux-en-y-gastric bypass

ACTIVE COMPARATOR

laparoscopic RYGB

Procedure: roux -en-y- gastric bypass

Interventions

roux -en-y- gastric bypass 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.

Roux-en-y-gastric bypass

intensive life style modification DIETARY_SUPPLEMENT

Weight loss will be induced using a VLCD (800-850 kcal/day; 59% carbohydrate, 13% fat, 26% protein, 2% fiber) with replacement meals for 2 months, followed by structured food reintroduction every 2-8 weeks (about 50% carbohydrate, 35% total fat, and 15% protein), and an ongoing structured program with follow-up visits up to 25% body weight loss

intensive lifestyle modifications

Eligibility Criteria

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

You may qualify if:

• Informed Consent signed before starting any procedure foreseen by the study;
• Liver Ultrasound shoving steatosis and Fibroscan\>9,5 KPa;
• NAFLD fibrosis score\>0,676;
• diagnosis of NASH with stage F3-F4 of fibrosis according to SAF score, documented by liver biopsy and no evidence of another form of liver disease;
• BMI≥ 30 and ≤50 kg/m2;
• Age 25-65 years.

You may not qualify if:

• Chronic liver disease other than NAFLD (e.g. hemochromatosis, viral or autoimmune hepatitis, Wilson's disease, α1 -antitrypsin deficiency);
• Presence of esophageal varices and/or ascites;
• INR ≥ 1,4;
• Platelet count ≤ 100000;
• Substantial alcohol consumption (\>20 g/day for women or \>30 g/day for men) and/or toxin exposure;
• Coronary event or procedure (myocardial infarction, unstable angina, coronary artery bypass, surgery or coronary angioplasty) in the previous 6 months;
• End stage renal failure;
• Participation in any other concurrent therapeutic clinical trial;
• Any other life-threatening, non-cardiac disease;
• Pregnancy;
• Type 1 diabetes, or LADA;
• Lipodystrophy;
• Abetalipoproteinemia;
• Interfering medications (e.g., amiodarone, methotrexate, tamoxifen, corticosteroids);
• Inability to give informed consent.

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead

Study Sites (1)

Mingrone Geltrude

Roma, 00188, Italy

Location

Related Publications (11)

• Younossi ZM. Non-alcoholic fatty liver disease - A global public health perspective. J Hepatol. 2019 Mar;70(3):531-544. doi: 10.1016/j.jhep.2018.10.033. Epub 2018 Nov 9.

  PMID: 30414863 RESULT

• Vilar Gomez E, Rodriguez De Miranda A, Gra Oramas B, Arus Soler E, Llanio Navarro R, Calzadilla Bertot L, Yasells Garcia A, Del Rosario Abreu Vazquez M. Clinical trial: a nutritional supplement Viusid, in combination with diet and exercise, in patients with nonalcoholic fatty liver disease. Aliment Pharmacol Ther. 2009 Nov 15;30(10):999-1009. doi: 10.1111/j.1365-2036.2009.04122.x. Epub 2009 Aug 18.

  PMID: 19691668 RESULT

• Dixon JB, Bhathal PS, Hughes NR, O'Brien PE. Nonalcoholic fatty liver disease: Improvement in liver histological analysis with weight loss. Hepatology. 2004 Jun;39(6):1647-54. doi: 10.1002/hep.20251.

  PMID: 15185306 RESULT

• Glass LM, Dickson RC, Anderson JC, Suriawinata AA, Putra J, Berk BS, Toor A. Total body weight loss of >/= 10 % is associated with improved hepatic fibrosis in patients with nonalcoholic steatohepatitis. Dig Dis Sci. 2015 Apr;60(4):1024-30. doi: 10.1007/s10620-014-3380-3. Epub 2014 Oct 30.

  PMID: 25354830 RESULT

• Mingrone G, Panunzi S, De Gaetano A, Guidone C, Iaconelli A, Nanni G, Castagneto M, Bornstein S, Rubino F. Bariatric-metabolic surgery versus conventional medical treatment in obese patients with type 2 diabetes: 5 year follow-up of an open-label, single-centre, randomised controlled trial. Lancet. 2015 Sep 5;386(9997):964-73. doi: 10.1016/S0140-6736(15)00075-6.

  PMID: 26369473 RESULT

• Lassailly G, Caiazzo R, Buob D, Pigeyre M, Verkindt H, Labreuche J, Raverdy V, Leteurtre E, Dharancy S, Louvet A, Romon M, Duhamel A, Pattou F, Mathurin P. Bariatric Surgery Reduces Features of Nonalcoholic Steatohepatitis in Morbidly Obese Patients. Gastroenterology. 2015 Aug;149(2):379-88; quiz e15-6. doi: 10.1053/j.gastro.2015.04.014. Epub 2015 Apr 25.

  PMID: 25917783 RESULT

• Lassailly G, Caiazzo R, Ntandja-Wandji LC, Gnemmi V, Baud G, Verkindt H, Ningarhari M, Louvet A, Leteurtre E, Raverdy V, Dharancy S, Pattou F, Mathurin P. Bariatric Surgery Provides Long-term Resolution of Nonalcoholic Steatohepatitis and Regression of Fibrosis. Gastroenterology. 2020 Oct;159(4):1290-1301.e5. doi: 10.1053/j.gastro.2020.06.006. Epub 2020 Jun 15.

  PMID: 32553765 RESULT

• Vilar-Gomez E, Martinez-Perez Y, Calzadilla-Bertot L, Torres-Gonzalez A, Gra-Oramas B, Gonzalez-Fabian L, Friedman SL, Diago M, Romero-Gomez M. Weight Loss Through Lifestyle Modification Significantly Reduces Features of Nonalcoholic Steatohepatitis. Gastroenterology. 2015 Aug;149(2):367-78.e5; quiz e14-5. doi: 10.1053/j.gastro.2015.04.005. Epub 2015 Apr 10.

  PMID: 25865049 RESULT

• Bedossa P, Poitou C, Veyrie N, Bouillot JL, Basdevant A, Paradis V, Tordjman J, Clement K. Histopathological algorithm and scoring system for evaluation of liver lesions in morbidly obese patients. Hepatology. 2012 Nov;56(5):1751-9. doi: 10.1002/hep.25889.

  PMID: 22707395 RESULT

• Angulo P, Hui JM, Marchesini G, Bugianesi E, George J, Farrell GC, Enders F, Saksena S, Burt AD, Bida JP, Lindor K, Sanderson SO, Lenzi M, Adams LA, Kench J, Therneau TM, Day CP. The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology. 2007 Apr;45(4):846-54. doi: 10.1002/hep.21496.

  PMID: 17393509 RESULT

• de Almeida SR, Rocha PR, Sanches MD, Leite VH, da Silva RA, Diniz MT, Diniz Mde F, Rocha AL. Roux-en-Y gastric bypass improves the nonalcoholic steatohepatitis (NASH) of morbid obesity. Obes Surg. 2006 Mar;16(3):270-8. doi: 10.1381/096089206776116462.

  PMID: 16545157 RESULT

MeSH Terms

Conditions

Weight Loss

Interventions

Gastric Bypass

Condition Hierarchy (Ancestors)

Body Weight Changes; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Bariatric Surgery; Bariatrics; Obesity Management; Therapeutics; Gastroenterostomy; Anastomosis, Surgical; Surgical Procedures, Operative; Digestive System Surgical Procedures

Study Officials

• geltrude mingrone, professor

  Policlinico A. Gemelli IRCCS

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: February 16, 2023
• First Posted: April 4, 2023
• Study Start: September 1, 2021
• Primary Completion: September 1, 2025
• Study Completion (Estimated): September 1, 2026
• Last Updated: April 4, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)