Non-Alcoholic Fatty Liver DiseaseNCT04501042
Investigation on the Role of Gut-liver Axis for Non-alcoholic Steatohepatitis Through Bariatric Surgery
An observational study of Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis, run by National Taiwan University Hospital at 1 site in Taiwan.
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. Read more about this study
- Who is it for?
- Ages 20 years and olderHealthy volunteers can take part
- Conditions the study is for
- Non-Alcoholic Fatty Liver Disease, Non-Alcoholic Steatohepatitis, Bariatric Surgery
- What is being tested?
- Bariatric surgery
- Type of treatment
- Surgery or procedure
- How many people
- 140 participants
- Where
- 1 siteTaiwan
- Study dates
- 16 May 2019to 1 Sep 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Morbidly obese patients who planned to receive bariatric surgery
Who may be able to join
- Age >20，morbidly obese patients who will receive bariatric surgery.
Who cannot join
- 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,
Show all 9Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Taiwan1 site, 1 recruiting
- Recruiting
National Taiwan University Hospital
Taipei, 100
Ming-Shiang Wu, MD, PhD, +886-2-23123456 ext. 65043, mingshiang@ntu.edu.tw
About this study
Official title: Investigation on Novel Route of Gut Microbiota Products for Bariatric Surgery to Improve Non-alcoholic Steatohepatitis and Development on Therapeutic Implications
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.
Read the detailed 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.
- 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.
- 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)
- Being tested
- Bariatric surgery
- Keywords
- Non-Alcoholic Steatohepatitis, Bariatric Surgery, Gut Microbiota, Gut-Liver Axis, Metabolomics, Metagenomics
- Medical subject headings
- Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bariatric surgeryProcedure or surgery
Also called Liver biopsy, Portal vein sampling
Bariatric surgery
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Procedure: Bariatric surgery | |
| NASH (after bariatric surgery) | age >20，morbid obesity receiving bariatric surgery and was proved NASH histologically. Data collected after bariatric surgery. Receives: Procedure: Bariatric surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Baseline and 6 months after bariatric surgery
Change of NAFLD severity measured by Fibroscan from baseline to the 6th month
Fibroscan (CAP and kPa)
Measured: 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 (%)
Measured: Baseline and 6 months after bariatric surgery
Change of NAFLD severity measured by magnetic resonance elastography from baseline to the
magnetic resonance elastography (kPa)
Measured: Baseline and 6 months after bariatric surgery
Secondary outcomes (6)
Change of gut microbiome profiles
fecal 16S ribosomal RNA sequencing and shotgun metagenome sequencing
Measured: Baseline, 1st month, 3rd month and 6th month after surgery
Change of body fluid metabolomic profiles
Metabolites in blood fluids measured by liquid chromatography mass spectrometry
Measured: Baseline, 1st month, 3rd month and 6th month after surgery
Change of Immune profiles
Immune cell phenotype patterns in body fluids measured by flow cytometry
Measured: Baseline, 1st month, 3rd month and 6th month after surgery
Change of gut permeability test
Lactulose/Mannitol challenge test
Measured: Baseline and 6 months after bariatric surgery
Change of gene expression profiles of liver tissue
gene expression measured by RNA-seq
Measured: Baseline and 6 months after bariatric surgery (if available)
Change of metabolomic profiles of liver tissue
Metabolites in liver tissue measured by liquid chromatography mass
Measured: Baseline and 6 months after bariatric surgery (if available)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2020
- Study start16 May 2019
- Primary completion1 Apr 2024 (estimated)
- Study completion1 Sep 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Alcoholic Fatty Liver DiseaseStudies of the same condition, open and under way.
- More trials run by National Taiwan University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 140 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Ministry of Science and Technology, Taiwan
- Responsible party
- Sponsor
- Investigators
- Ming-Shiang Wu, MD, PhD, Principal investigator, National Taiwan University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04501042
- Sponsor's protocol ID
- 201903037RIND
- Status last verified
- Sep 2021
- First submitted
- 22 Jul 2020
- Last updated
- 27 Sep 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigation on Novel Route of Gut Microbiota Products for Bariatric Surgery to Improve Non-alcoholic Steatohepatitis and Development on Therapeutic Implications
- ClinicalTrials.gov ID
- NCT04501042
- Acronym / sponsor ID
- 201903037RIND
- Keywords
- Non-Alcoholic Steatohepatitis, Bariatric Surgery, Gut Microbiota, Gut-Liver Axis, Metabolomics, Metagenomics
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 140 participants (estimated)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Collaborators
- Ministry of Science and Technology, Taiwan
- Study start
- 16 May 2019 (actual)
- Primary completion
- 1 Apr 2024 (estimated)
- Study completion
- 1 Sep 2024 (estimated)
- First posted
- 6 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
- 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.
- 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)
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 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) | – | Procedure: Bariatric surgeryage >20，morbid obesity receiving bariatric surgery and was proved NASH histologically. Data collected before bariatric surgery. |
| NASH (after bariatric surgery) | – | Procedure: Bariatric surgeryage >20，morbid obesity receiving bariatric surgery and was proved NASH histologically. Data collected after bariatric surgery. |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Morbidly obese patients who planned to receive bariatric surgery
Key inclusion criteria (1 listed)
- Age >20，morbidly obese patients who will receive bariatric surgery.
Key exclusion criteria (9 listed)
- 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,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bariatric surgeryAlso: Liver biopsy, Portal vein samplingBariatric surgery | Procedure or surgery | NASH (after bariatric surgery), NASH (before bariatric surgery) |
Primary outcome
Change of NAFLD severity score (histology) from baseline to the 6th month
Time frame: Baseline and 6 months after bariatric surgery
Liver biopsy will be performed before and after surgery (if available) to acquire histology evaluation
Change of NAFLD severity measured by Fibroscan from baseline to the 6th month
Time frame: Baseline and 6 months after bariatric surgery
Fibroscan (CAP and kPa)
Change of NAFLD severity measured by MRI proton density fat fraction from baseline to the
Time frame: Baseline and 6 months after bariatric surgery
MRI proton density fat fraction (%)
Change of NAFLD severity measured by magnetic resonance elastography from baseline to the
Time frame: Baseline and 6 months after bariatric surgery
magnetic resonance elastography (kPa)
6 secondary outcomes
Change of gut microbiome profiles
Time frame: Baseline, 1st month, 3rd month and 6th month after surgery
Change of body fluid metabolomic profiles
Time frame: Baseline, 1st month, 3rd month and 6th month after surgery
Change of Immune profiles
Time frame: Baseline, 1st month, 3rd month and 6th month after surgery
Change of gut permeability test
Time frame: Baseline and 6 months after bariatric surgery
Change of gene expression profiles of liver tissue
Time frame: Baseline and 6 months after bariatric surgery (if available)
Change of metabolomic profiles of liver tissue
Time frame: Baseline and 6 months after bariatric surgery (if available)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Sep 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ming-Shiang Wu, MD, PhD principal investigator
National Taiwan University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis, run by National Taiwan University Hospital at 1 site in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 27 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Wei-Kai Wu (+886-2-23717101, weikaiwu0115@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change of NAFLD severity score (histology) from baseline to the 6th month (time frame: Baseline and 6 months after bariatric surgery). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Sep 2022.