Synbiotics Interventions for Managing Cirrhosis and Its Complications

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Cirrhosis, Liver, Metagonimiasis

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A 10-g packet of lactulose oral solution and three capsules of probiotics +entecavir group<br>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<br>* Orally administered Entecavir 0.5 mg, once a day. For six months<br>Drug: A 10-g packet of lactulose oral solution and three capsules of probiotics<br>* 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.<br>|
| Placebo Comparator: A 10-g packet of glucose oral solution and three capsules of starch+entecavir group<br>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<br>* Orally administered Entecavir 0.5 mg, once a day. For six months<br>Dietary Supplement: A 10-g packet of glucose oral solution and three capsules of starch<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cirrhosis, Liver, Synbiotics