Clinical trial NCT05798702: Fibrosis Reduction in Non Alcoholic Steatohepatitis
Official title: Fibrosis Reduction in Non Alcoholic Steatohepatitis: the Effects of Weight Loss vs Metabolic Surgery
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: NASH With Fibrosis
Weight Loss
Bariatric Surgery Candidate
Lead sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Sponsor class: OTHER
First posted: 2023-04-04
Enrollment: 20
Sex: ALL
Minimum age (years): 25
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

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.

Detailed description: Materials and Methods: The Investigators will screen patients with obesity, NAFLD fibrosis score (NFS) \>0.676 and FibroScan \> 9.5 kPA who have a high probability of NASH with advanced stage of fibrosis.

Participants will undergo liver biopsy to make diagnosis according to the Steatosis Activity Fibrosis (SAF) score algorithm. Subjects with BMI ≥ 30 and ≤50 kg/m2, age 25-65 years and F3-F4 fibrosis stage at liver biopsy will be included and randomized 1:1 to RYGB or VLCD. Anthropometric parameters, body composition with DEXA and liver function with blood samples will be assessed at the enrolment. A mixed meal metabolic test will be also performed to evaluate insulin sensitivity and secretion. These procedures will be repeated after 25% weight loss. Expectation: The Investigators expect a reduction of 2 points of histological fibrosis after 25% weight loss following either metabolic surgery or dieting. The investigators foresee also reversal of NASH, improvement of metabolic syndrome and glycemic control, changes in insulin sensitivity and secretion, changes in lipid profile, in NASH liver markers, in Fibroscan variables and in body composition

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: histological reduction of fibrosis
timeFrame: 2 years
Secondary outcomes:
measure: Liver histology
timeFrame: 2 years
measure: Liver Markers
timeFrame: 2 years
measure: Non-alcoholic Fatty Liver Disease Fibrosis score
timeFrame: 2 years
measure: Fibrosis-4 (FIB-4) Index
timeFrame: 2 years
measure: Fibroscan
timeFrame: 2 years
Other outcomes:
Locations:
city: Roma
country: Italy
facility: Mingrone Geltrude
Study officials:
affiliation: Policlinico A. Gemelli IRCCS
name: geltrude mingrone, professor
role: PRINCIPAL_INVESTIGATOR
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