Investigation on the Role of Gut-liver Axis for Non-alcoholic Steatohepatitis Through Bariatric Surgery

NCT04501042 | Unknown

• 1 other identifier: 201903037RIND
• Study Type: observational
• Target: 140
• Locations: 1 country
• Sites: 1

Brief Summary

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Non-alcoholic steatohepatitis (NASH) is an aggressive form of NAFLD with remarkable inflammatory features which may cause advanced fibrosis and liver cancer. So far there is no FDA-approved drug for treating NASH. A 10% weight loss by life style modification is a standard recommendation to treat NASH which achieves only 10-20% success rate in clinical practice. Thus, the development of therapeutics to prevent and treat NASH is certainly an unmet need. For now, the mechanism of how simple steatosis progresses to NASH remains unclear and accumulating evidences suggest the role of gut microbiota may be essential. Studies have also noted the bariatric surgery effectively improve diabetes and NASH with significant alterations in the composition and function of gut microbiome. In this study, the investigators aim to investigate the role of gut microbiota in the pathophysiology of NASH by comparing NAFLD severity, gut microbiome, metabolomics, immune profiles among patients before and after the bariatric surgery. With these efforts, the investigators wish to decipher the mechanism of how bariatric surgery may improve NASH through changing the gut microbiota and find out microbe-associated molecular signatures between NASH and NAFLD through this study.

Conditions

Non-Alcoholic Fatty Liver Disease; Non-Alcoholic Steatohepatitis; Bariatric Surgery

Keywords

Non-Alcoholic Steatohepatitis; Bariatric Surgery; Gut Microbiota; Gut-Liver Axis; Metabolomics; Metagenomics

Outcome Measures

Primary Outcomes (4)

• Change of NAFLD severity score (histology) from baseline to the 6th month

  Liver biopsy will be performed before and after surgery (if available) to acquire histology evaluation

  Baseline and 6 months after bariatric surgery

• Change of NAFLD severity measured by Fibroscan from baseline to the 6th month

  Fibroscan (CAP and kPa)

  Baseline and 6 months after bariatric surgery

• Change of NAFLD severity measured by MRI proton density fat fraction from baseline to the

  MRI proton density fat fraction (%)

  Baseline and 6 months after bariatric surgery

• Change of NAFLD severity measured by magnetic resonance elastography from baseline to the

  magnetic resonance elastography (kPa)

  Baseline and 6 months after bariatric surgery

Secondary Outcomes (6)

• Change of gut microbiome profiles

  Baseline, 1st month, 3rd month and 6th month after surgery

• Change of body fluid metabolomic profiles

  Baseline, 1st month, 3rd month and 6th month after surgery

• Change of Immune profiles

  Baseline, 1st month, 3rd month and 6th month after surgery

• Change of gut permeability test

  Baseline and 6 months after bariatric surgery

• Change of gene expression profiles of liver tissue

  Baseline and 6 months after bariatric surgery (if available)

Study Arms (4)

Obese patients tissue proved NASH

age \>20，morbid obesity who will receive bariatric surgery, tissue proved NASH

Obese patients tissue proved NAFL

age \>20，morbid obesity who will receive bariatric surgery, tissue proved NAFL

NASH (before bariatric surgery)

age \>20，morbid obesity receiving bariatric surgery and was proved NASH histologically. Data collected before bariatric surgery.

Procedure: Bariatric surgery

NASH (after bariatric surgery)

age \>20，morbid obesity receiving bariatric surgery and was proved NASH histologically. Data collected after bariatric surgery.

Procedure: Bariatric surgery

Interventions

Bariatric surgery PROCEDURE

Bariatric surgery

Also known as: Liver biopsy, Portal vein sampling

NASH (after bariatric surgery); NASH (before bariatric surgery)

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Morbidly obese patients who planned to receive bariatric surgery

You may qualify if:

• Age \>20，morbidly obese patients who will receive bariatric surgery.

You may not qualify if:

• Average daily alcohol intake \>20 grams,
• Hepatitis B carriers, Hepatitis C carriers,
• people with liver disease caused by other causes
• liver cirrhosis,
• diseases related to abnormal blood coagulation,
• inflammatory bowel disease,
• routine use of steroids or immunity Inhibitors and other immunomodulatory drugs
• ursodeoxycholic and other drugs that affect bile acid metabolism
• those who have used antibiotics or probiotics within one month

Sponsors & Collaborators

• National Taiwan University Hospital: lead
• Ministry of Science and Technology, Taiwan: collaborator

Study Sites (1)

National Taiwan University Hospital

Taipei, 100, Taiwan

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Peripheral blood and portal vein (during operation) samples will be collected in this study. Plasma for biochemistry and metabolomics measurement, Buffy coat for NAFLD-susceptible single nucleotide polymorphism (SNP) detection (i.e. PNPLA3, TM6SF2...etc), peripheral blood mononuclear cell (PBMC) for flow cytometry, urine samples for lactulose/mannitol measurement (gut permeability test), fecal samples for metagenomics and metabolomics studies.

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

Bariatric Surgery

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Bariatrics; Obesity Management; Therapeutics; Surgical Procedures, Operative

Study Officials

• Ming-Shiang Wu, MD, PhD

  National Taiwan University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wei-Kai Wu

CONTACT

+886-2-23717101; weikaiwu0115@gmail.com

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2020
• First Posted: August 6, 2020
• Study Start: May 16, 2019
• Primary Completion: April 1, 2024
• Study Completion: September 1, 2024
• Last Updated: September 27, 2022

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)