Alterations of Gut Microbiota and Metabolites in ALD Patients

NCT ID: NCT05448144

Last Updated: 2023-08-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

200 participants

Study Classification

OBSERVATIONAL

Study Start Date

2022-06-01

Study Completion Date

2024-12-31

Brief Summary

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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

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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

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Liver Disease; Alcohol-Related Gut Microbiota

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Alcohol-associated liver disease

drinking, had fatty liver, hepatitis, or hepatic cirrhosis

Collect stool and blood samples from patients

Intervention Type OTHER

Collect stool and blood samples from patients

Purely drinking

drinking, but had no fatty liver and hepatitis.

Collect stool and blood samples from patients

Intervention Type OTHER

Collect stool and blood samples from patients

Healthy control

no drinking and no liver diseases.

Collect stool and blood samples from patients

Intervention Type OTHER

Collect stool and blood samples from patients

Interventions

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Collect stool and blood samples from patients

Collect stool and blood samples from patients

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

1\. The group of ALD:

1. aged \>18 years;
2. patients who meet the diagnostic criteria of ALD in Chinese Guideline for the Prevention and Management of Alcoholic Liver Disease (2018 Update);
3. history of chronic heavy alcohol consumption;
4. with relatively complete clinical data and good compliance.

2\. The group of purely drinking:

1. aged \>18 years;
2. history of chronic alcohol consumption;
3. no evidence of fatty liver, hepatitis or liver injury.

3\. The group of healthy control:

1. aged \>18 years;
2. without history of alcohol consumption;
3. no evidence of fatty liver, hepatitis or liver injury.

Exclusion Criteria

1. with hepatocellular carcinoma or hepatic metastases;
2. 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);
3. 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;
4. combined with severe organic lesions of other organs;
5. pregnant and lactating women.
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

OTHER

Sponsor Role lead

Responsible Party

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Huikuan Chu, MD

Associate chief physician

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Huikuan Chu, M.D.

Role: STUDY_DIRECTOR

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Locations

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Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Huikuan Chu, M.D.

Role: CONTACT

+8613554105386

Wenkang Gao, Dr.

Role: CONTACT

+8618838022896

Facility Contacts

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Huikuan Chu, M.D.

Role: primary

+8613554105386

Wenkang Gao, Dr.

Role: backup

+8618838022896

References

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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.

Reference Type RESULT
PMID: 31606552 (View on PubMed)

Duan 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.

Reference Type RESULT
PMID: 31723265 (View on PubMed)

Chu 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.

Reference Type RESULT
PMID: 30171065 (View on PubMed)

Jiang 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.

Reference Type RESULT
PMID: 32671585 (View on PubMed)

Chu 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.

Reference Type RESULT
PMID: 30416839 (View on PubMed)

Provided Documents

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Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Related Links

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https://gcp.whuh.com/index.aspx

This web provides information of Human Subjects Protection in this study

Other Identifiers

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UHCT22032

Identifier Type: -

Identifier Source: org_study_id

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