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Fibrosis Reduction in Non Alcoholic Steatohepatitis (FRIN)

Primary Purpose

NASH With Fibrosis, Weight Loss, Bariatric Surgery Candidate

Status

Active

Phase

Not Applicable

Locations

Italy

Study Type

Interventional

Intervention

roux -en-y- gastric bypass

intensive life style modification

About this trial

This is an interventional diagnostic trial for NASH With Fibrosis

Eligibility Criteria

25 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Mingrone Geltrude

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

intensive lifestyle modifications

Roux-en-y-gastric bypass

Arm Description

VLCD 800-850 Kcal/day

laparoscopic RYGB

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Liver histology

Reversal of NASH: number of partcipant with a NAFLD activity score (NAS: from 0 to 8) < 3; Changes in Fibroscan evaluation: number of participant with a FibroScan <9.5 kPa.

Liver Markers

Changes in liver markers: number of participant with a significant reduction of AST and ALT from baseline;

Non-alcoholic Fatty Liver Disease Fibrosis score

Changes in Non-alcoholic Fatty Liver Disease Fibrosis score from baseline

Fibrosis-4 (FIB-4) Index

Changes in Fibrosis-4 (FIB-4) Index for Liver Fibrosis from baseline;

Fibroscan

Changes in Fibroscan evaluation: number of participant with a FibroScan <9.5 kPa.

Full Information

NCT ID

NCT05798702

First Posted

February 16, 2023

Last Updated

March 22, 2023

Sponsor

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

1. Study Identification

Unique Protocol Identification Number

NCT05798702

Brief Title

Fibrosis Reduction in Non Alcoholic Steatohepatitis

Acronym

FRIN

Official Title

Fibrosis Reduction in Non Alcoholic Steatohepatitis: the Effects of Weight Loss vs Metabolic Surgery

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

September 1, 2021 (Actual)

Primary Completion Date

September 1, 2025 (Anticipated)

Study Completion Date

September 1, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

NASH With Fibrosis, Weight Loss, Bariatric Surgery Candidate

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

intensive lifestyle modifications

Arm Type

Active Comparator

Arm Description

VLCD 800-850 Kcal/day

Arm Title

Roux-en-y-gastric bypass

Arm Type

Active Comparator

Arm Description

laparoscopic RYGB

Intervention Type

Procedure

Intervention Name(s)

roux -en-y- gastric bypass

Intervention Description

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.

Intervention Type

Dietary Supplement

Intervention Name(s)

intensive life style modification

Intervention Description

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

Primary Outcome Measure Information:

Title

histological reduction of fibrosis

Description

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

Time Frame

2 years

Secondary Outcome Measure Information:

Title

Liver histology

Description

Reversal of NASH: number of partcipant with a NAFLD activity score (NAS: from 0 to 8) < 3; Changes in Fibroscan evaluation: number of participant with a FibroScan <9.5 kPa.

Time Frame

2 years

Title

Liver Markers

Description

Changes in liver markers: number of participant with a significant reduction of AST and ALT from baseline;

Time Frame

2 years

Title

Non-alcoholic Fatty Liver Disease Fibrosis score

Description

Changes in Non-alcoholic Fatty Liver Disease Fibrosis score from baseline

Time Frame

2 years

Title

Fibrosis-4 (FIB-4) Index

Description

Changes in Fibrosis-4 (FIB-4) Index for Liver Fibrosis from baseline;

Time Frame

2 years

Title

Fibroscan

Description

Changes in Fibroscan evaluation: number of participant with a FibroScan <9.5 kPa.

Time Frame

2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

25 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

geltrude mingrone, professor

Organizational Affiliation

Policlinico A. Gemelli IRCCS

Official's Role

Principal Investigator

Facility Information:

Facility Name

Mingrone Geltrude

City

Roma

ZIP/Postal Code

00188

Country

Italy

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

30414863

Citation

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Results Reference

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PubMed Identifier

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Citation

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Results Reference

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Citation

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Results Reference

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Citation

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Citation

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Citation

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Citation

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Fibrosis Reduction in Non Alcoholic Steatohepatitis

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