Back to resultsExplore the Efficacy and Safety of FMT With Different Bacterial Doses in the Treatment of Hepatic Encephalopathy
Primary Purpose
Hepatic Encephalopathy
Status
Active
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Fecal Microbiota Transplantation
Sponsored by
About this trial
This is an interventional treatment trial for Hepatic Encephalopathy focused on measuring hepatic encephalopathy, fecal microbiota transplantation
Eligibility Criteria
Inclusion Criteria: 18-75 years old; 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; MELD score i ≤ 25 points (score range is 6-40, the higher the score is, the more serious the disease is) Meet the requirements for receiving FMT through nasojejunal tube The subject (or guardian) has signed the informed consent form Exclusion Criteria: Patients expected to undergo liver transplantation within 1 month 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 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) Heavy drinking in recent 12 weeks Have used drugs that affect the psychometric score of hepatic encephalopathy (PHEs), such as antidepressants and sedative hypnosis, in recent 4 weeks Patients who are allergic to antibiotics before treatment Infection (pathogen obtained through sterile sites) Patients with chronic endogenous gastrointestinal diseases, such as inflammatory bowel disease (ulcerative colitis, Crohn's disease or microscopic colitis), irritable bowel syndrome Suffering from neurological diseases, such as stroke, epilepsy, dementia and Parkinson's disease Pregnant or lactating patients (urine pregnancy test will be used for examination) Patients who cannot provide informed consent Patients who are unwilling or unable to undergo indwelling nasojejunal tube Other researchers think it is not suitable to be included in this experiment
Sites / Locations
- Shulan (Hangzhou) Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Low dose of group
High dose of group
Arm Description
Complete the fecal bacteria transplantation through the upper digestive tract: Intestinal preparation: Amoxicillin 0.5g bid, metronidazole 0.4g bid and levofloxacin 0.5g qd for 3 days. FMT: After 12h of antibiotic discontinuation, the total amount of bacterial liquid was 400ml, 100ml each time, Q12h, 2 days after 12h of antibiotic discontinuation.
Complete the fecal bacteria transplantation through the upper digestive tract: Intestinal preparation: Amoxicillin 0.5g bid, metronidazole 0.4g bid and levofloxacin 0.5g qd for 3 days. FMT: After 12h of antibiotic discontinuation, the total amount of bacterial liquid was 800ml, 100ml each time, Q12h, 4 days .
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
FMT related serious adverse events
FMT related serious adverse events
FMT related adverse events
FMT related adverse events
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05669651
Brief Title
Explore the Efficacy and Safety of FMT With Different Bacterial Doses in the Treatment of Hepatic Encephalopathy
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 1, 2022 (Actual)
Primary Completion Date
June 30, 2025 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Hainv Gao
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief 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.
Detailed 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatic Encephalopathy
Keywords
hepatic encephalopathy, fecal microbiota transplantation
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderOutcomes Assessor
Allocation
Randomized
Enrollment
100 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Low dose of group
Arm Type
Experimental
Arm Description
Complete the fecal bacteria transplantation through the upper digestive tract:
Intestinal preparation: Amoxicillin 0.5g bid, metronidazole 0.4g bid and levofloxacin 0.5g qd for 3 days.
FMT: After 12h of antibiotic discontinuation, the total amount of bacterial liquid was 400ml, 100ml each time, Q12h, 2 days after 12h of antibiotic discontinuation.
Arm Title
High dose of group
Arm Type
Experimental
Arm Description
Complete the fecal bacteria transplantation through the upper digestive tract:
Intestinal preparation: Amoxicillin 0.5g bid, metronidazole 0.4g bid and levofloxacin 0.5g qd for 3 days.
FMT: After 12h of antibiotic discontinuation, the total amount of bacterial liquid was 800ml, 100ml each time, Q12h, 4 days .
Intervention Type
Other
Intervention Name(s)
Fecal Microbiota Transplantation
Intervention 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.
Primary Outcome Measure Information:
Title
Incidence of the first breakthrough episode of hepatic encephalopathy after FMT.
Description
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.
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
FMT related serious adverse events
Description
FMT related serious adverse events
Time Frame
one month
Title
FMT related adverse events
Description
FMT related adverse events
Time Frame
one month
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
18-75 years old;
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;
MELD score i ≤ 25 points (score range is 6-40, the higher the score is, the more serious the disease is)
Meet the requirements for receiving FMT through nasojejunal tube
The subject (or guardian) has signed the informed consent form
Exclusion Criteria:
Patients expected to undergo liver transplantation within 1 month
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
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)
Heavy drinking in recent 12 weeks
Have used drugs that affect the psychometric score of hepatic encephalopathy (PHEs), such as antidepressants and sedative hypnosis, in recent 4 weeks
Patients who are allergic to antibiotics before treatment
Infection (pathogen obtained through sterile sites)
Patients with chronic endogenous gastrointestinal diseases, such as inflammatory bowel disease (ulcerative colitis, Crohn's disease or microscopic colitis), irritable bowel syndrome
Suffering from neurological diseases, such as stroke, epilepsy, dementia and Parkinson's disease
Pregnant or lactating patients (urine pregnancy test will be used for examination)
Patients who cannot provide informed consent
Patients who are unwilling or unable to undergo indwelling nasojejunal tube
Other researchers think it is not suitable to be included in this experiment
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hainv Gao, doctor
Organizational Affiliation
Shulan (Hangzhou) Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
Shulan (Hangzhou) Hospital
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310000
Country
China
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
27720916
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 Independent of Other Extrahepatic Organ Failures. Clin Gastroenterol Hepatol. 2017 Apr;15(4):565-574.e4. doi: 10.1016/j.cgh.2016.09.157. Epub 2016 Oct 5.
Results Reference
result
PubMed Identifier
31038755
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 Phase 1, Randomized, Placebo-Controlled Trial. Hepatology. 2019 Nov;70(5):1690-1703. doi: 10.1002/hep.30690. Epub 2019 Jun 18. Erratum In: Hepatology. 2020 Oct;72(4):1501.
Results Reference
result
PubMed Identifier
30706423
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.
Results Reference
result
PubMed Identifier
23565181
Citation
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 minimal hepatic encephalopathy. PLoS One. 2013;8(4):e60042. doi: 10.1371/journal.pone.0060042. Epub 2013 Apr 2.
Results Reference
result
PubMed Identifier
29462280
Citation
McDonald LC, Gerding DN, Johnson S, Bakken JS, Carroll KC, Coffin SE, Dubberke ER, Garey KW, Gould CV, Kelly C, Loo V, Shaklee Sammons J, Sandora TJ, Wilcox MH. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018 Mar 19;66(7):e1-e48. doi: 10.1093/cid/cix1085.
Results Reference
result
PubMed Identifier
29691757
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.
Results Reference
result
PubMed Identifier
26618921
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.
Results Reference
result
PubMed Identifier
22728514
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, Nieuwdorp M. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology. 2012 Oct;143(4):913-6.e7. doi: 10.1053/j.gastro.2012.06.031. Epub 2012 Jun 20. Erratum In: Gastroenterology. 2013 Jan;144(1):250.
Results Reference
result
PubMed Identifier
25857665
Citation
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. Gastroenterology. 2015 Jul;149(1):102-109.e6. doi: 10.1053/j.gastro.2015.04.001. Epub 2015 Apr 7.
Results Reference
result
PubMed Identifier
26824647
Citation
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.
Results Reference
result
PubMed Identifier
9770652
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.
Results Reference
result
PubMed Identifier
22699609
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.
Results Reference
result
PubMed Identifier
20203603
Citation
Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, Nielsen T, Pons N, Levenez F, Yamada T, Mende DR, Li J, Xu J, Li S, Li D, Cao J, Wang B, Liang H, Zheng H, Xie Y, Tap J, Lepage P, Bertalan M, Batto JM, Hansen T, Le Paslier D, Linneberg A, Nielsen HB, Pelletier E, Renault P, Sicheritz-Ponten T, Turner K, Zhu H, Yu C, Li S, Jian M, Zhou Y, Li Y, Zhang X, Li S, Qin N, Yang H, Wang J, Brunak S, Dore J, Guarner F, Kristiansen K, Pedersen O, Parkhill J, Weissenbach J; MetaHIT Consortium; Bork P, Ehrlich SD, Wang J. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010 Mar 4;464(7285):59-65. doi: 10.1038/nature08821.
Results Reference
result
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Explore the Efficacy and Safety of FMT With Different Bacterial Doses in the Treatment of Hepatic Encephalopathy
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