Explore the Efficacy and Safety of FMT With Different Bacterial Doses in the Treatment of Hepatic Encephalopathy

Hepatic Encephalopathy Clinical Trial

Official title:

A Multicenter, Prospective, Randomized Controlled Study to Explore the Efficacy and Safety of Fecal Microbiota Transplantation With Different Bacterial Doses in the Treatment of Recurrent Hepatic Encephalopathy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05669651
• Other study ID #: Shulan (Hang zhou)2
• Status: Active, not recruiting
• Phase: N/A
• Start date: December 1, 2022
• Est. completion date: December 31, 2025

Study information

• Verified date: March 2023
• Source: Shulan (Hangzhou) Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Hepatic encephalopathy (HE) is one of the most serious complications of end-stage liver disease and an independent predictor of death in patients with liver cirrhosis. Recurrent hepatic encephalopathy is defined as recurrent hepatic encephalopathy after rifaximin combined with lactulose treatment. This project designs a prospective, multicenter cohort study on the treatment of recurrent hepatic encephalopathy with fecal microbiota transplantation, carries out the comparison of fecal microbiota transplantation with different amounts of bacteria, and the dynamic sequencing of the macro genome of the recipient's stool, compares the effectiveness and safety of fecal microbiota transplantation with different amounts of bacteria in the treatment of recurrent hepatic encephalopathy, and explores the internal mechanism of different effects, providing a new idea for the treatment of recurrent HE in clinical practice.

Description:

Fecal microbiota transplantation (FMT) refers to the transplantation of functional flora from healthy people's feces into patients' intestines to rebuild new intestinal flora and achieve the treatment of intestinal and parenteral diseases. In this study, 100 patients with recurrent hepatic encephalopathy were randomly divided into 1:1 groups to receive FMT with different amounts of bacteria, observe the therapeutic effect and adverse reactions of hepatic encephalopathy, and evaluate the effectiveness and safety of the two groups of patients. At the same time, the blood and stool samples of patients with recurrent hepatic encephalopathy before and after FMT were collected clinically, the composition of bile acid and other metabolites in stool and serum samples was analyzed, and the effective core flora was identified to clarify the mechanism of intestinal bacteria transplantation for the treatment of recurrent hepatic encephalopathy.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 100
• Est. completion date: December 31, 2025
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. 18-75 years old;

2. At least two obvious episodes of hepatic encephalopathy (West-Haven = 2 ) were related to cirrhosis in the first 6 months, and the condition was in remission (West Haven grade 0 or 1) at the time of enrollment. The attack of hepatic encephalopathy caused by gastrointestinal bleeding requiring at least 2 units of blood transfusion, the use of sedatives, renal failure requiring dialysis or central nervous system injury is not recorded as the previous attack;

3. MELD score i = 25 points (score range is 6-40, the higher the score is, the more serious the disease is)

4. Meet the requirements for receiving FMT through nasojejunal tube

5. The subject (or guardian) has signed the informed consent form

Exclusion Criteria:

1. Patients expected to undergo liver transplantation within 1 month

2. Patients with known causes of hepatic encephalopathy (including gastrointestinal bleeding and placement of portal systemic shunt or transjugular intrahepatic portal systemic shunt) within 3 months

3. There are chronic renal insufficiency (creatinine level > 2.0mg/dl), respiratory insufficiency, anemia (HB < 8g / dl), electrolyte abnormalities (serum sodium < 125umol / L; serum calcium > 10mg / dl [2.5umol / l]; or serum potassium < 2.5 mmol / L)

4. Heavy drinking in recent 12 weeks

5. Have used drugs that affect the psychometric score of hepatic encephalopathy (PHEs), such as antidepressants and sedative hypnosis, in recent 4 weeks

6. Patients who are allergic to antibiotics before treatment

7. Infection (pathogen obtained through sterile sites)

8. Patients with chronic endogenous gastrointestinal diseases, such as inflammatory bowel disease (ulcerative colitis, Crohn's disease or microscopic colitis), irritable bowel syndrome

9. Suffering from neurological diseases, such as stroke, epilepsy, dementia and Parkinson's disease

10. Pregnant or lactating patients (urine pregnancy test will be used for examination)

11. Patients who cannot provide informed consent

12. Patients who are unwilling or unable to undergo indwelling nasojejunal tube

13. Other researchers think it is not suitable to be included in this experiment

Related Conditions & MeSH terms

• Brain Diseases
• Hepatic Encephalopathy

Intervention

Other:
• Fecal Microbiota Transplantation
Fecal microbiota transplantation (FMT) refers to the transplantation of functional flora from healthy people's feces into patients' intestines to rebuild new intestinal flora and achieve the treatment of intestinal and parenteral diseases. In this study, 100 patients with recurrent hepatic encephalopathy were randomly divided into 1:1 groups to receive FMT with different amounts of bacteria, observe the therapeutic effect and adverse reactions of hepatic encephalopathy, and evaluate the effectiveness and safety of the two groups of patients. At the same time, the blood and stool samples of patients with recurrent hepatic encephalopathy before and after FMT were collected clinically, the composition of bile acid and other metabolites in stool and serum samples was analyzed, and the effective core flora was identified to clarify the mechanism of intestinal bacteria transplantation for the treatment of recurrent hepatic encephalopathy.

Locations

Country	Name	City	State
China	Shulan (Hangzhou) Hospital	Hangzhou	Zhejiang

Sponsors (1)

Lead Sponsor	Collaborator
Hainv Gao

Country where clinical trial is conducted

China, 

References & Publications (13)

Bajaj JS, Heuman DM, Sanyal AJ, Hylemon PB, Sterling RK, Stravitz RT, Fuchs M, Ridlon JM, Daita K, Monteith P, Noble NA, White MB, Fisher A, Sikaroodi M, Rangwala H, Gillevet PM. Modulation of the metabiome by rifaximin in patients with cirrhosis and mini — View Citation

Bajaj JS, O'Leary JG, Tandon P, Wong F, Garcia-Tsao G, Kamath PS, Maliakkal B, Biggins SW, Thuluvath PJ, Fallon MB, Subramanian RM, Vargas HE, Lai J, Thacker LR, Reddy KR. Hepatic Encephalopathy Is Associated With Mortality in Patients With Cirrhosis Inde — View Citation

Bajaj JS, Salzman NH, Acharya C, Sterling RK, White MB, Gavis EA, Fagan A, Hayward M, Holtz ML, Matherly S, Lee H, Osman M, Siddiqui MS, Fuchs M, Puri P, Sikaroodi M, Gillevet PM. Fecal Microbial Transplant Capsules Are Safe in Hepatic Encephalopathy: A P — View Citation

Butterworth RF. Hepatic Encephalopathy in Cirrhosis: Pathology and Pathophysiology. Drugs. 2019 Feb;79(Suppl 1):17-21. doi: 10.1007/s40265-018-1017-0. — View Citation

DuPont HL. Review article: the antimicrobial effects of rifaximin on the gut microbiota. Aliment Pharmacol Ther. 2016 Jan;43 Suppl 1:3-10. doi: 10.1111/apt.13434. — View Citation

Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature. 2012 Jun 13;486(7402):207-14. doi: 10.1038/nature11234. — View Citation

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Moayyedi P, Surette MG, Kim PT, Libertucci J, Wolfe M, Onischi C, Armstrong D, Marshall JK, Kassam Z, Reinisch W, Lee CH. Fecal Microbiota Transplantation Induces Remission in Patients With Active Ulcerative Colitis in a Randomized Controlled Trial. Gastr — View Citation

Olson MA, Cuff L. Molecular docking of superantigens with class II major histocompatibility complex proteins. J Mol Recognit. 1997 Nov-Dec;10(6):277-89. doi: 10.1002/(SICI)1099-1352(199711/12)10:63.0.CO;2-X. — View Citation

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Sender R, Fuchs S, Milo R. Are We Really Vastly Outnumbered? Revisiting the Ratio of Bacterial to Host Cells in Humans. Cell. 2016 Jan 28;164(3):337-40. doi: 10.1016/j.cell.2016.01.013. — View Citation

Vrieze A, Van Nood E, Holleman F, Salojarvi J, Kootte RS, Bartelsman JF, Dallinga-Thie GM, Ackermans MT, Serlie MJ, Oozeer R, Derrien M, Druesne A, Van Hylckama Vlieg JE, Bloks VW, Groen AK, Heilig HG, Zoetendal EG, Stroes ES, de Vos WM, Hoekstra JB, Nieu — View Citation

Zhang F, Cui B, He X, Nie Y, Wu K, Fan D; FMT-standardization Study Group. Microbiota transplantation: concept, methodology and strategy for its modernization. Protein Cell. 2018 May;9(5):462-473. doi: 10.1007/s13238-018-0541-8. Epub 2018 Apr 24. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of the first breakthrough episode of hepatic encephalopathy after FMT.	West-Haven Grade =2 that occurs within 12 weeks is defined as the first breakthrough episode of hepatic encephalopathy after FMT. Breakthrough attack patients identified as FMT is invalid, no breakthrough attack patients identified as FMT is effective, at the same time compare the advantages and disadvantages of two ways of FMT efficacy.	12 weeks
Secondary	FMT related serious adverse events	FMT related serious adverse events	one month
Secondary	FMT related adverse events	FMT related adverse events	one month