Alterations of Gut Microbiota and Serum Biochemical Markers in DILI Patients

NCT ID: NCT05465642

Last Updated: 2023-08-31

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

90 participants

Study Classification

OBSERVATIONAL

Study Start Date

2022-07-04

Study Completion Date

2024-12-31

Brief Summary

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Drug-induced liver injury is a leading cause of acute liver failure worldwide and one of the least understood areas in hepatology research. Increasing evidence has shown that drug-induced liver injury is associated with gut microbiota.

Detailed Description

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Background:

Drug-induced liver injury(DILI) refers to the liver injury induced by all kinds of drugs and is the leading cause of acute liver failure worldwide. China has a large population base and a wide variety of clinical drugs, and it is common for the population to use drugs irregularly. Therefore, the incidence of DILI is increasing year by year. The pathogenesis of DILI is complicated, and there are often multiple mechanisms successively or altogether. As a result of the same effect, it is particularly important to study the pathogenesis of DILI and find its therapeutic target. Increasing evidence shows that DILI is related to the gut microbiota, which provides broader insights and opportunities for understanding and treating this disease.

Aims:

We aim to map the alterations of gut microbiota and serum biochemical markers in patients with DILI, and to investigate the effects and mechanisms of key strains on the development of DILI, 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 will be collected at baseline. Fecal samples will be subject to 16S rRNA amplicon sequencing. Serum samples were taken for metabolomics detection.

Anticipated Results:

Compared to the healthy control group, patients with DILI will suffer from gut microbiota dysbiosis and have more microbes and microbial genes associated with inflammation and injury. The levels of serum biochemical markers are associated with the severity of DILI.

Implications and Future Studies:

Results of altered gut microbiome and serum biochemical markers could provide potential targets for manipulating intestinal microbiota to prevent or treat DILI.

Conditions

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Drug-induced Liver Injury Gut Microbiota Biochemical Markers

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Drug-induced liver injury

history of taking hepatotoxic drugs, liver injury.

Collect stool and blood samples from patients

Intervention Type OTHER

Collect stool and blood samples from patients

Healthy control

no liver disease or other disease

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 DILI:

1. aged \>18 years;
2. patients who meet the diagnostic criteria of DILI in Guidelines for Diagnosis and Treatment of Drug-induced Liver Injury;
3. history of taking hepatotoxic drugs;
4. with relatively complete clinical data and good compliance.

2\. The group of healthy control:

1. aged \>18 years;
2. no history of liver disease and other diseases.

Exclusion Criteria

1. with hepatocellular carcinoma (HCC) 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, alcoholic liver disease, autoimmune liver disease, immunoglobulin G4-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, wuhan

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

Li Zhang, Dr.

Role: backup

+8618756533130

References

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Hartmann P, Chu H, Duan Y, Schnabl B. Gut microbiota in liver disease: too much is harmful, nothing at all is not helpful either. Am J Physiol Gastrointest Liver Physiol. 2019 May 1;316(5):G563-G573. doi: 10.1152/ajpgi.00370.2018. Epub 2019 Feb 15.

Reference Type RESULT
PMID: 30767680 (View on PubMed)

Wu G, Win S, Than TA, Chen P, Kaplowitz N. Gut Microbiota and Liver Injury (I)-Acute Liver Injury. Adv Exp Med Biol. 2020;1238:23-37. doi: 10.1007/978-981-15-2385-4_3.

Reference Type RESULT
PMID: 32323178 (View on PubMed)

Gong S, Lan T, Zeng L, Luo H, Yang X, Li N, Chen X, Liu Z, Li R, Win S, Liu S, Zhou H, Schnabl B, Jiang Y, Kaplowitz N, Chen P. Gut microbiota mediates diurnal variation of acetaminophen induced acute liver injury in mice. J Hepatol. 2018 Jul;69(1):51-59. doi: 10.1016/j.jhep.2018.02.024. Epub 2018 Mar 8.

Reference Type RESULT
PMID: 29524531 (View on PubMed)

Schneider KM, Elfers C, Ghallab A, Schneider CV, Galvez EJC, Mohs A, Gui W, Candels LS, Wirtz TH, Zuehlke S, Spiteller M, Myllys M, Roulet A, Ouzerdine A, Lelouvier B, Kilic K, Liao L, Nier A, Latz E, Bergheim I, Thaiss CA, Hengstler JG, Strowig T, Trautwein C. Intestinal Dysbiosis Amplifies Acetaminophen-Induced Acute Liver Injury. Cell Mol Gastroenterol Hepatol. 2021;11(4):909-933. doi: 10.1016/j.jcmgh.2020.11.002. Epub 2020 Nov 12.

Reference Type RESULT
PMID: 33189892 (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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UHCT22354

Identifier Type: -

Identifier Source: org_study_id

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