Synbiotics Interventions for Managing Cirrhosis and Its Complications

Phase 4

Completed

• Conditions: Cirrhosis, Liver; Metagonimiasis
• Interventions: Drug: Entecavir 0.5 mg; Dietary Supplement: A 10-g packet of glucose oral solution and three capsules of starch; Drug: A 10-g packet of lactulose oral solution and three capsules of probiotics

• Registration Number: NCT05687409
• Lead Sponsor: First Affiliated Hospital of Zhejiang University

Brief Summary

Background Liver cirrhosis is commonly accompanied by intestinal dysbiosis and metabolic defects. Many clinical trials have shown microbiota-targeting strategies represent promising interventions for managing cirrhosis and its complications. However, the influences of the intestinal metagenomes and metabolic profiles of patients have not been fully elucidated.

Methods administered lactulose, Clostridium butyricum, and Bifidobacterium longum infantis as a synbiotic and used shotgun metagenomics and non-targeted metabolomics to characterize the results.

Detailed Description

Not available

Study Timeline

• Study Start: 2019-11-24
• Primary Completion: 2021-05-24
• Study Completion: 2022-10-24
• Status Verified: 2022-11
• Study First Submitted: 2022-11-25
• Study First Submitted QC: 2023-01-12
• Last Update Submitted: 2023-01-12
• Study First Posted: 2023-01-18
• Last Update Posted: 2023-01-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

• ① Hepatitis B cirrhosis was diagnosed by clinical biochemistry and imaging.

  • CTP rating is a-b.

    • There was a previous liver cirrhosis complication, including ascites, spontaneous peritonitis, massive gastrointestinal bleeding, liver coma, etc.

      • Over 18 years old. ⑤ Under 90 years old.

        • The patient or family member signs the informed consent form.

Exclusion Criteria

• ① The CTP of liver cirrhosis was evaluated as grade C.

  • Other types of cirrhosis such as primary biliary cirrhosis.

    • Pregnancy status. ④ Have a history of diabetes, renal insufficiency, gastrointestinal surgery, etc.

      • Antibiotics, PPI preparations and microecological preparations (including yogurt) have been used in the past 8 weeks.

        • Have a history of narcotic drug abuse, drug abuse, or mental illness. ⑦ Patients and their families do not agree to sign the informed consent form. ⑧ Under 18 years old or over 90 years old.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A 10-g packet of lactulose oral solution and three capsules of probiotics +entecavir group	Entecavir 0.5 mg	10-g packet of lactulose oral solution and three capsules of probiotics +entecavir group:Adults with histologically confirmed stable cirrhosis and BMI \< 25 kg m-2 were enrolled and assigned to receive boxes labeled A or B: one for the synbiotic, including a 10-g packet of lactulose oral solution and three capsules of probiotics (each containing \> 4.2×106 CFU Clostridium butyricum and \> 4.2×105 CFU Bifidobacterium longum infantis). Participants orally administered the contents three times daily after meals. Entecavir 5mg, once a day. All of the above lasted for six months.
A 10-g packet of glucose oral solution and three capsules of starch+entecavir group	A 10-g packet of glucose oral solution and three capsules of starch	A 10-g packet of glucose oral solution and three capsules of starch+entecavir group:Adults with histologically confirmed stable cirrhosis and BMI \< 25 kg m-2 were enrolled and assigned to receive boxes labeled A or B: one for the synbiotic, including a 10-g packet of lactulose oral solution and three capsules of probiotics (each containing \> 4.2×106 CFU Clostridium butyricum and \> 4.2×105 CFU Bifidobacterium longum infantis). Participants orally administered the contents three times daily after meals. Entecavir 5mg, once a day. All of the above lasted for six months.
A 10-g packet of glucose oral solution and three capsules of starch+entecavir group	Entecavir 0.5 mg	A 10-g packet of glucose oral solution and three capsules of starch+entecavir group:Adults with histologically confirmed stable cirrhosis and BMI \< 25 kg m-2 were enrolled and assigned to receive boxes labeled A or B: one for the synbiotic, including a 10-g packet of lactulose oral solution and three capsules of probiotics (each containing \> 4.2×106 CFU Clostridium butyricum and \> 4.2×105 CFU Bifidobacterium longum infantis). Participants orally administered the contents three times daily after meals. Entecavir 5mg, once a day. All of the above lasted for six months.
A 10-g packet of lactulose oral solution and three capsules of probiotics +entecavir group	A 10-g packet of lactulose oral solution and three capsules of probiotics	10-g packet of lactulose oral solution and three capsules of probiotics +entecavir group:Adults with histologically confirmed stable cirrhosis and BMI \< 25 kg m-2 were enrolled and assigned to receive boxes labeled A or B: one for the synbiotic, including a 10-g packet of lactulose oral solution and three capsules of probiotics (each containing \> 4.2×106 CFU Clostridium butyricum and \> 4.2×105 CFU Bifidobacterium longum infantis). Participants orally administered the contents three times daily after meals. Entecavir 5mg, once a day. All of the above lasted for six months.

Primary Outcome Measures

Name	Time	Method
Assessing the intestinal microbiota of 120 cirrhotic and healthy participants through fecal metagenomics	Up to 12 months	fecal metagenomics was used to assess the intestinal microbiota of participants.
Liver CT to assess cirrhosis in 70 cirrhotic participants	Up to 11 months	Liver CT was used to evaluate the liver cirrhosis of 70 cirrhotic participants
Metabolomics to assess the metabolites of the 120 cirrhotic and healthy participants' intestinal microbiota including polyketides(Casimiroedine μmol/L),Benzenoids(Olmesartan μmol/L),Organoheterocyclic compounds(Amlexanox μmol/L) and etc.	Up to 12 months	Metabolomics was used to assess the metabolites of the participants' intestinal microbiota.

Trial Locations

Locations (1)

The First Affiliated Hospital, College of Medicine, Zhejiang University; 🇨🇳 Hangzhou, Zhejiang, China