Liver Disease; Alcohol-RelatedNCT05448144
Alterations of Gut Microbiota and Metabolites in ALD Patients
An observational study of Liver Disease; Alcohol-Related and Gut Microbiota, run by Union Hospital, Tongji Medical College, Huazhong University of Science and Technology at 1 site in China.
Trial summary
Alcohol-associated liver disease is one of the most prevalent liver diseases worldwide, and the leading cause of liver transplantation in the U.S. Alcohol-related liver disease is associated with changes in the intestinal microbiota and metabolites. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Liver Disease; Alcohol-Related, Gut Microbiota
- What is being tested?
- Collect stool and blood samples from patients
- How many people
- 200 participants
- Where
- 1 siteChina
- Study dates
- 1 Jun 2022to Dec 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 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Patients and healthy control will be recruited mainly from the outpatient or inpatient departments of Wuhan Union Hospital.
Who may be able to join
- 1. The group of ALD:
- aged >18 years;
- patients who meet the diagnostic criteria of ALD in Chinese Guideline for the Prevention and Management of Alcoholic Liver Disease (2018 Update);
- history of chronic heavy alcohol consumption;
- with relatively complete clinical data and good compliance.
- 2. The group of purely drinking:
Show all 13Show fewer
- aged >18 years;
- history of chronic alcohol consumption;
- no evidence of fatty liver, hepatitis or liver injury.
- 3. The group of healthy control:
- aged >18 years;
- without history of alcohol consumption;
- no evidence of fatty liver, hepatitis or liver injury.
Who cannot join
- with hepatocellular carcinoma or hepatic metastases;
- combined with infectious liver diseases, such as hepatitis A virus, hepatitis B virus, hepatitis C virus, hepatitis D virus, hepatitis E virus and human immunodeficiency virus (HIV);
- combined with non-infectious liver diseases, such as non-alcoholic fatty liver disease, drug-induced hepatitis, autoimmune liver disease, Immunoglobulin G subclass 4-related liver disease, Wilson's disease, alpha 1-antitrypsin deficiency, Budd-Chiari syndrome, and other congenital liver diseases;
- combined with severe organic lesions of other organs;
- pregnant and lactating women.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei, 430022
Huikuan Chu, M.D., +8613554105386, 2012xh0827@hust.edu.cn
Wenkang Gao, Dr., +8618838022896, gwkmed@163.com
About this study
Official title: Alterations of Gut Microbiota and Metabolites in Asian Patients With Alcohol-associated Liver Disease
Alcohol-associated liver disease is one of the most prevalent liver diseases worldwide, and the leading cause of liver transplantation in the U.S. Alcohol-related liver disease is associated with changes in the intestinal microbiota and metabolites.
Read the detailed description
Backgrounds:
Alcohol-associated liver disease (ALD) is a common disease caused by alcohol use disorder (AUD), ranging from asymptomatic liver steatosis to alcohol-associated hepatitis (AH), alcoholic cirrhosis and potentially, hepatocellular carcinoma (HCC). ALD is the most common reason for liver transplantation in the United States. Globally, about 2 million people die from liver disease each year and up to 50% of the death with cirrhosis can be attributed to alcohol consumption. In Europe, it has been estimated that 60%-80% of liver-related deaths can be attributed to alcohol consumption. Currently, the pathogenetic mechanisms have not been fully elucidated, but they might be related to oxidative stress, acetaldehyde-induced toxicity, cytokine and chemokine-induced inflammation. There is no effective therapeutic method for ALD till now except for liver transplantation. Recent studies have reported that gut microbiota has an intimate relationship with ALD, which provides broader insights and opportunities for understanding and treating this disease.
Aims:
We aim to map the alterations of gut microbiota and metabolites in patients with different levels of ALD, and to investigate the effects and mechanisms of key strains and their metabolites on the development of ALD, providing a theoretical basis and potential targets for its treatment.
Methods:
Patients who meet the inclusion criteria will sign informed consent, their demographic data, clinical labs, serum, and feces for shotgun metagenomics will be collected at baseline.
Anticipated Results:
Compared to healthy control group, patients with AH or alcohol-associated hepatic cirrhosis will suffer from microbiota dysbiosis and have more microbes and microbial genes associated with inflammation and fibrosis. Gut microbiota-derived metabolites may exacerbate the severity of ALD. Several microorganisms or metabolites can be used as prognostic markers.
Implications and Future Studies:
Results of altered gut microbiome and metabolites could provide potential targets for manipulating intestinal microbiota to prevent or treat ALD.
- Conditions
- Liver Disease; Alcohol-Related, Gut Microbiota
- Being tested
- Collect stool and blood samples from patients
- Keywords
- Alcohol-associated liver disease, Gut microbiota, Metabonomics
- Medical subject headings
- Liver Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Collect stool and blood samples from patientsOther
Collect stool and blood samples from patients
| Study group | Role | What they receive |
|---|---|---|
| Alcohol-associated liver disease | drinking, had fatty liver, hepatitis, or hepatic cirrhosis Receives: Other: Collect stool and blood samples from patients | |
| Purely drinking | drinking, but had no fatty liver and hepatitis. Receives: Other: Collect stool and blood samples from patients | |
| Healthy control | no drinking and no liver diseases. Receives: Other: Collect stool and blood samples from patients |
What is being measured
The primary outcome is the main question the study is designed to answer.
The alterations of gut microbiota in different groups
The alterations will be detected by genome sequencing
Measured: When subjects are enrolled
The alterations of gut metabolites in different group
The alterations will be detected by metabolomics
Measured: When subjects are enrolled
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jul 2022
- Study start1 Jun 2022
- Primary completionJun 2024 (estimated)
- Study completionDec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Liver Disease; Alcohol-RelatedStudies of the same condition, open and under way.
- More trials run by Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyThe 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Huikuan Chu, MD, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Investigators
- Huikuan Chu, M.D., Study director, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05448144
- Sponsor's protocol ID
- UHCT22032
- Status last verified
- Aug 2023
- First submitted
- 2 Jul 2022
- Last updated
- 29 Aug 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Chu H, Duan Y, Lang S, Jiang L, Wang Y, Llorente C, Liu J, Mogavero S, Bosques-Padilla F, Abraldes JG, Vargas V, Tu XM, Yang L, Hou X, Hube B, Starkel P, Schnabl B. The Candida albicans exotoxin candidalysin promotes alcohol-associated liver disease. J Hepatol. 2020 Mar;72(3):391-400. doi: 10.1016/j.jhep.2019.09.029. Epub 2019 Oct 10.
PubMed 31606552Duan Y, Llorente C, Lang S, Brandl K, Chu H, Jiang L, White RC, Clarke TH, Nguyen K, Torralba M, Shao Y, Liu J, Hernandez-Morales A, Lessor L, Rahman IR, Miyamoto Y, Ly M, Gao B, Sun W, Kiesel R, Hutmacher F, Lee S, Ventura-Cots M, Bosques-Padilla F, Verna EC, Abraldes JG, Brown RS Jr, Vargas V, Altamirano J, Caballeria J, Shawcross DL, Ho SB, Louvet A, Lucey MR, Mathurin P, Garcia-Tsao G, Bataller R, Tu XM, Eckmann L, van der Donk WA, Young R, Lawley TD, Starkel P, Pride D, Fouts DE, Schnabl B. Bacteriophage targeting of gut bacterium attenuates alcoholic liver disease. Nature. 2019 Nov;575(7783):505-511. doi: 10.1038/s41586-019-1742-x. Epub 2019 Nov 13.
PubMed 31723265Chu H, Duan Y, Yang L, Schnabl B. Small metabolites, possible big changes: a microbiota-centered view of non-alcoholic fatty liver disease. Gut. 2019 Feb;68(2):359-370. doi: 10.1136/gutjnl-2018-316307. Epub 2018 Aug 31.
PubMed 30171065Jiang L, Chu H, Gao B, Lang S, Wang Y, Duan Y, Schnabl B. Transcriptomic Profiling Identifies Novel Hepatic and Intestinal Genes Following Chronic Plus Binge Ethanol Feeding in Mice. Dig Dis Sci. 2020 Dec;65(12):3592-3604. doi: 10.1007/s10620-020-06461-6. Epub 2020 Jul 15.
PubMed 32671585Chu H, Williams B, Schnabl B. Gut microbiota, fatty liver disease, and hepatocellular carcinoma. Liver Res. 2018 Mar;2(1):43-51. doi: 10.1016/j.livres.2017.11.005. Epub 2018 Feb 21.
PubMed 30416839
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Alterations of Gut Microbiota and Metabolites in Asian Patients With Alcohol-associated Liver Disease
- ClinicalTrials.gov ID
- NCT05448144
- Acronym / sponsor ID
- UHCT22032
- Conditions
- Liver Disease; Alcohol-Related, Gut Microbiota
- Keywords
- Alcohol-associated liver disease, Gut microbiota, Metabonomics
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyUniversity, hospital or other
- Study start
- 1 Jun 2022 (actual)
- Primary completion
- Jun 2024 (estimated)
- Study completion
- Dec 2024 (estimated)
- First posted
- 7 Jul 2022 (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.
Alcohol-associated liver disease is one of the most prevalent liver diseases worldwide, and the leading cause of liver transplantation in the U.S. Alcohol-related liver disease is associated with changes in the intestinal microbiota and metabolites.
Detailed description
Backgrounds:
Alcohol-associated liver disease (ALD) is a common disease caused by alcohol use disorder (AUD), ranging from asymptomatic liver steatosis to alcohol-associated hepatitis (AH), alcoholic cirrhosis and potentially, hepatocellular carcinoma (HCC). ALD is the most common reason for liver transplantation in the United States. Globally, about 2 million people die from liver disease each year and up to 50% of the death with cirrhosis can be attributed to alcohol consumption. In Europe, it has been estimated that 60%-80% of liver-related deaths can be attributed to alcohol consumption. Currently, the pathogenetic mechanisms have not been fully elucidated, but they might be related to oxidative stress, acetaldehyde-induced toxicity, cytokine and chemokine-induced inflammation. There is no effective therapeutic method for ALD till now except for liver transplantation. Recent studies have reported that gut microbiota has an intimate relationship with ALD, which provides broader insights and opportunities for understanding and treating this disease.
Aims:
We aim to map the alterations of gut microbiota and metabolites in patients with different levels of ALD, and to investigate the effects and mechanisms of key strains and their metabolites on the development of ALD, providing a theoretical basis and potential targets for its treatment.
Methods:
Patients who meet the inclusion criteria will sign informed consent, their demographic data, clinical labs, serum, and feces for shotgun metagenomics will be collected at baseline.
Anticipated Results:
Compared to healthy control group, patients with AH or alcohol-associated hepatic cirrhosis will suffer from microbiota dysbiosis and have more microbes and microbial genes associated with inflammation and fibrosis. Gut microbiota-derived metabolites may exacerbate the severity of ALD. Several microorganisms or metabolites can be used as prognostic markers.
Implications and Future Studies:
Results of altered gut microbiome and metabolites could provide potential targets for manipulating intestinal microbiota to prevent or treat ALD.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Alcohol-associated liver disease | – | Other: Collect stool and blood samples from patientsdrinking, had fatty liver, hepatitis, or hepatic cirrhosis |
| Purely drinking | – | Other: Collect stool and blood samples from patientsdrinking, but had no fatty liver and hepatitis. |
| Healthy control | – | Other: Collect stool and blood samples from patientsno drinking and no liver diseases. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Patients and healthy control will be recruited mainly from the outpatient or inpatient departments of Wuhan Union Hospital.
Key inclusion criteria (13 listed)
- aged >18 years;
- patients who meet the diagnostic criteria of ALD in Chinese Guideline for the Prevention and Management of Alcoholic Liver Disease (2018 Update);
- history of chronic heavy alcohol consumption;
- with relatively complete clinical data and good compliance.
- aged >18 years;
Key exclusion criteria (5 listed)
- with hepatocellular carcinoma or hepatic metastases;
- combined with infectious liver diseases, such as hepatitis A virus, hepatitis B virus, hepatitis C virus, hepatitis D virus, hepatitis E virus and human immunodeficiency virus (HIV);
- combined with non-infectious liver diseases, such as non-alcoholic fatty liver disease, drug-induced hepatitis, autoimmune liver disease, Immunoglobulin G subclass 4-related liver disease, Wilson's disease, alpha 1-antitrypsin deficiency, Budd-Chiari syndrome, and other congenital liver diseases;
- combined with severe organic lesions of other organs;
- pregnant and lactating women.
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 |
|---|---|---|
| Collect stool and blood samples from patientsCollect stool and blood samples from patients | Other | Alcohol-associated liver disease, Healthy control, Purely drinking |
Primary outcome
The alterations of gut microbiota in different groups
Time frame: When subjects are enrolled
The alterations will be detected by genome sequencing
The alterations of gut metabolites in different group
Time frame: When subjects are enrolled
The alterations will be detected by metabolomics
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2023.
- Results publication: PubMed 31606552Chu H, Duan Y, Lang S, Jiang L, Wang Y, Llorente C, Liu J, Mogavero S, Bosques-Padilla F, Abraldes JG, Vargas V, Tu XM, Yang L, Hou X, Hube B, Starkel P, Schnabl B. The Candida albicans exotoxin candidalysin promotes alcohol-associated liver disease. J Hepatol. 2020 Mar;72(3):391-400. doi: 10.1016/j.jhep.2019.09.029. Epub 2019 Oct 10.
- Results publication: PubMed 31723265Duan Y, Llorente C, Lang S, Brandl K, Chu H, Jiang L, White RC, Clarke TH, Nguyen K, Torralba M, Shao Y, Liu J, Hernandez-Morales A, Lessor L, Rahman IR, Miyamoto Y, Ly M, Gao B, Sun W, Kiesel R, Hutmacher F, Lee S, Ventura-Cots M, Bosques-Padilla F, Verna EC, Abraldes JG, Brown RS Jr, Vargas V, Altamirano J, Caballeria J, Shawcross DL, Ho SB, Louvet A, Lucey MR, Mathurin P, Garcia-Tsao G, Bataller R, Tu XM, Eckmann L, van der Donk WA, Young R, Lawley TD, Starkel P, Pride D, Fouts DE, Schnabl B. Bacteriophage targeting of gut bacterium attenuates alcoholic liver disease. Nature. 2019 Nov;575(7783):505-511. doi: 10.1038/s41586-019-1742-x. Epub 2019 Nov 13.
- Results publication: PubMed 30171065Chu H, Duan Y, Yang L, Schnabl B. Small metabolites, possible big changes: a microbiota-centered view of non-alcoholic fatty liver disease. Gut. 2019 Feb;68(2):359-370. doi: 10.1136/gutjnl-2018-316307. Epub 2018 Aug 31.
- Results publication: PubMed 32671585Jiang L, Chu H, Gao B, Lang S, Wang Y, Duan Y, Schnabl B. Transcriptomic Profiling Identifies Novel Hepatic and Intestinal Genes Following Chronic Plus Binge Ethanol Feeding in Mice. Dig Dis Sci. 2020 Dec;65(12):3592-3604. doi: 10.1007/s10620-020-06461-6. Epub 2020 Jul 15.
- Results publication: PubMed 30416839Chu H, Williams B, Schnabl B. Gut microbiota, fatty liver disease, and hepatocellular carcinoma. Liver Res. 2018 Mar;2(1):43-51. doi: 10.1016/j.livres.2017.11.005. Epub 2018 Feb 21.
- This web provides information of Human Subjects Protection in this studyLink provided by the sponsor.
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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.
Huikuan Chu, M.D. study director
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
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 Liver Disease; Alcohol-Related and Gut Microbiota, run by Union Hospital, Tongji Medical College, Huazhong University of Science and Technology at 1 site in China.
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 13 inclusion and 5 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 29 Aug 2023. 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 China. 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 Huikuan Chu, M.D. (+8613554105386, 2012xh0827@hust.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The alterations of gut microbiota in different groups (time frame: When subjects are enrolled). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05448144, which also lists 5 linked publications.
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 29 Aug 2023.