Synbiotics Interventions for Managing Cirrhosis and Its Complications

Alterations in the Intestinal Microbiome and Metabolic Profile of Patients With Cirrhosis Supplemented With Lactulose, Clostridium Butyricum, and Bifidobacterium Longum Infantis: a Randomized Placebo-controlled Trial

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.

Study Overview

• Status: Completed
• Conditions: Cirrhosis, Liver; Metagonimiasis
• Intervention / Treatment: Drug: Entecavir 0.5 mg; Drug: A 10-g packet of lactulose oral solution and three capsules of probiotics; Dietary supplement: A 10-g packet of glucose oral solution and three capsules of starch

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • The First Affiliated Hospital, College of Medicine, Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A 10-g packet of lactulose oral solution and three capsules of probiotics +entecavir group; 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.	Drug: Entecavir 0.5 mg; Orally administered Entecavir 0.5 mg, once a day. For six months; Drug: A 10-g packet of lactulose oral solution and three capsules of probiotics; 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. For six months.
Placebo Comparator: 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+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.	Drug: Entecavir 0.5 mg; Orally administered Entecavir 0.5 mg, once a day. For six months; Dietary supplement: 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. Participants orally administered the contents three times daily after meals. For six months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Liver CT to assess cirrhosis in 70 cirrhotic participants	Liver CT was used to evaluate the liver cirrhosis of 70 cirrhotic participants	Up to 11 months
Assessing the intestinal microbiota of 120 cirrhotic and healthy participants through fecal metagenomics	fecal metagenomics was used to assess the intestinal microbiota of participants.	Up to 12 months
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.	Metabolomics was used to assess the metabolites of the participants' intestinal microbiota.	Up to 12 months

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): November 24, 2019
• Primary Completion (Actual): May 24, 2021
• Study Completion (Actual): October 24, 2022

Study Registration Dates

• First Submitted: November 25, 2022
• First Submitted That Met QC Criteria: January 12, 2023
• First Posted (Actual): January 18, 2023

Study Record Updates

• Last Update Posted (Actual): January 18, 2023
• Last Update Submitted That Met QC Criteria: January 12, 2023
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Cirrhosis, Liver; Synbiotics
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Infections; Liver Diseases; Parasitic Diseases; Helminthiasis; Fibrosis; Liver Cirrhosis; Trematode Infections; Anti-Infective Agents; Antiviral Agents; Gastrointestinal Agents; Lactulose; Entecavir; Pharmaceutical Solutions
• Other Study ID Numbers: wuzhongwenzju

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: share date: within 6 months after project finish. Website: Resman. http://www.medresman.org.cn/pub/cn/proj/search.aspx

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No