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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04501042
Other study ID # 201903037RIND
Secondary ID
Status Recruiting
Phase
First received
Last updated
Start date May 16, 2019
Est. completion date September 1, 2024

Study information

Verified date September 2021
Source National Taiwan University Hospital
Contact Wei-Kai Wu
Phone +886-2-23717101
Email weikaiwu0115@gmail.com
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial 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.


Description:

The investigators anticipate to recruit 140 morbidly obese patients who will receive bariatric surgery including 100 patients receiving sleeve gastrectomy (SG) and 40 receiving gastric bypass surgery (GB). Liver biopsy will be performed during the operation to confirm the histological scores of NAFLD severity. The investigators expect to have 50% NASH and 50% NAFL patients from these morbidly obese patients based on previous domestic data. (i.e. 50 patients receiving SG to have NASH and 50 patients receiving SG to have NAFL; 20 patients receiving GB to have NASH and 20 patients receiving GB to have NAFL.) In this study, the investigators have two study objectives which are as follows. 1. The first objective is to discover potential mechanisms among gut-liver axis for preventing or promoting NAFL to NASH by comparing (1) fecal microbiome composition and metabolomics, (2) peripheral blood biochemistry, metabolomics, immune cell phenotypes, and cytokines (3) portal vein biochemistry, metabolomics, immune cell phenotypes, and cytokines (4) Liver metabolomics and RNA-seq (5) gut permeability test (lactulose/mannitol challenge) (6) host genetic susceptibility for NAFLD (PNPLA3 and TM6SF2) between the tissue-proved NASH and NAFL patients in this study with a cross-sectional comparison. 2. The second objective is to longitudinally investigate the potential mechanisms of bariatric surgery for improving NASH via a gut-microbiota dependent pathway. Clinical and experimental data before (baseline) and after (1st, 3rd, 6th months) bariatric surgery will be collected which include (1) non-invasive evaluation of NAFLD severity (Fibroscan, MRI-PDFF (proton density fat fraction) and MRE), (2) blood biochemistry, metabolomics, immune cell phenotypes, and cytokines (3) fecal microbiome and metabolomics (4) gut permeability test (5) liver biopsy histology (if available)


Recruitment information / eligibility

Status Recruiting
Enrollment 140
Est. completion date September 1, 2024
Est. primary completion date April 1, 2024
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 20 Years and older
Eligibility Inclusion Criteria: Age >20,morbidly obese patients who will receive bariatric surgery. Exclusion Criteria: - 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

Study Design


Related Conditions & MeSH terms


Intervention

Procedure:
Bariatric surgery
Bariatric surgery

Locations

Country Name City State
Taiwan National Taiwan University Hospital Taipei

Sponsors (2)

Lead Sponsor Collaborator
National Taiwan University Hospital Ministry of Science and Technology, Taiwan

Country where clinical trial is conducted

Taiwan, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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
Primary Change of NAFLD severity measured by Fibroscan from baseline to the 6th month Fibroscan (CAP and kPa) Baseline and 6 months after bariatric surgery
Primary 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
Primary 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 Change of gut microbiome profiles fecal 16S ribosomal RNA sequencing and shotgun metagenome sequencing Baseline, 1st month, 3rd month and 6th month after surgery
Secondary Change of body fluid metabolomic profiles Metabolites in blood fluids measured by liquid chromatography mass spectrometry Baseline, 1st month, 3rd month and 6th month after surgery
Secondary Change of Immune profiles Immune cell phenotype patterns in body fluids measured by flow cytometry Baseline, 1st month, 3rd month and 6th month after surgery
Secondary Change of gut permeability test Lactulose/Mannitol challenge test Baseline and 6 months after bariatric surgery
Secondary Change of gene expression profiles of liver tissue gene expression measured by RNA-seq Baseline and 6 months after bariatric surgery (if available)
Secondary Change of metabolomic profiles of liver tissue Metabolites in liver tissue measured by liquid chromatography mass Baseline and 6 months after bariatric surgery (if available)
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