An Early Phase 1 interventional study of Fecal Microbiota Transplantation and Rifaximin、Lactulose in Hepatic Encephalopathy, Fecal Microbiota Transplantation and TIPS, sponsored by Air Force Military Medical University, China. Recruiting at 1 site in China. Open to participants aged 18 Years to 75 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-07-06.
Sponsored by Air Force Military Medical University, China · Early Phase 1, Interventional, and Treatment
This is a single-center, prospective, open-label, parallel-group exploratory clinical study designed to evaluate the safety and preliminary efficacy of fecal microbiota transplantation combined with standard medical therapy in patients with refractory overt hepatic encephalopathy after transjugular intrahepatic portosystemic shunt. The study also aims to explore whether adjunctive prebiotic supplementation may improve clinical outcomes and support gut microbiota reconstruction after fecal microbiota transplantation.
A total of 26 participants with recurrent overt hepatic encephalopathy after TIPS despite standard therapy with rifaximin and lactulose will be enrolled. All participants will continue to receive standard medical therapy, including rifaximin and lactulose. During an episode of overt hepatic encephalopathy, all participants will receive fecal microbiota transplantation via a nasojejunal tube at a dose of 100 mL per administration, twice daily, for 3 consecutive days. Participants will be assigned in a 1:1 ratio to either the fecal microbiota transplantation group or the fecal microbiota transplantation plus prebiotic group. Participants in the combination group will receive dietary fiber prebiotic supplementation at 24 g/day for 4 weeks in addition to the same fecal microbiota transplantation and standard medical therapy.
Participants will be followed for up to 6 months. The primary efficacy assessment will focus on recurrence of hepatic encephalopathy, including recurrence rate, time to first recurrence, episode grade, and duration. Secondary assessments will include time to reversal of hepatic encephalopathy, West Haven grade, blood ammonia, liver and kidney function, inflammatory markers, liver function scores, neurocognitive function, and changes in gut microbiota composition. Safety assessments will include adverse events, fecal microbiota transplantation-related adverse events, infection, worsening hepatic encephalopathy, hospitalization, and serious adverse events. This study is expected to provide preliminary clinical evidence for a microbiota-based therapeutic strategy in patients with refractory overt hepatic encephalopathy after TIPS.
Hepatic encephalopathy is one of the most common and clinically significant complications after transjugular intrahepatic portosystemic shunt. After TIPS, portosystemic shunting may increase the systemic exposure to gut-derived neurotoxins and inflammatory mediators, thereby increasing the risk of overt hepatic encephalopathy. Although lactulose and rifaximin are widely used as standard medical therapy, some patients continue to experience recurrent overt hepatic encephalopathy despite adequate treatment. For patients with refractory overt hepatic encephalopathy after TIPS, current therapeutic options remain limited, particularly in terms of rapid recovery of consciousness, prevention of recurrence, and restoration of gut microbial homeostasis.
Fecal microbiota transplantation may provide a microbiota-based therapeutic approach by reshaping the intestinal microbial ecosystem, modulating gut-derived toxin production, improving intestinal barrier and metabolic function, and regulating the gut-liver-brain axis. Previous studies have suggested that fecal microbiota transplantation may be safe and potentially effective in patients with cirrhosis-related hepatic encephalopathy. However, clinical evidence remains limited in patients with refractory overt hepatic encephalopathy specifically occurring after TIPS. In addition, prebiotics may support the growth and engraftment of beneficial bacterial taxa after fecal microbiota transplantation by providing fermentable dietary substrates. Therefore, this study is designed to evaluate the safety and preliminary efficacy of fecal microbiota transplantation combined with standard therapy in patients with refractory overt hepatic encephalopathy after TIPS, and to compare the clinical and microbiome-related effects of fecal microbiota transplantation with or without adjunctive prebiotic supplementation.
This is a single-center, prospective, open-label, parallel-group exploratory clinical study. A total of 26 eligible participants with refractory overt hepatic encephalopathy after TIPS will be enrolled. Eligible participants will be adults aged 18 to 75 years who have successfully undergone covered-stent TIPS and have experienced at least two episodes of overt hepatic encephalopathy with West Haven grade 2 or higher within 6 months despite treatment with rifaximin and lactulose. Participants must also be suitable for fecal microbiota transplantation via a nasojejunal tube and able to tolerate tube placement and subsequent infusion procedures. Key exclusion criteria include active major gastrointestinal bleeding or perforation, severely impaired intestinal barrier function, congenital or acquired immunodeficiency, recent high-risk immunosuppressive or cytotoxic therapy, hepatic or gastrointestinal malignancy, spontaneous bacterial peritonitis, Budd-Chiari syndrome, severe cardiac, renal, or pulmonary dysfunction, unstable vital signs, recent gastrointestinal surgery, planned liver transplantation within 6 months, recent fecal microbiota transplantation, alcohol dependence, use of medications that may affect neuropsychiatric status, other neuropsychiatric disorders, pregnancy or lactation, and poor compliance as judged by the investigator.
All enrolled participants will continue to receive standard medical therapy. Standard therapy consists of rifaximin 0.4 g three times daily, with a total daily dose of 1200 mg, and lactulose 25 mL twice daily, adjusted as clinically needed. During an episode of overt hepatic encephalopathy, all participants will receive fecal microbiota transplantation via a nasojejunal tube. The fecal microbiota suspension will be administered at 100 mL per infusion, twice daily, for 3 consecutive days. The fecal microbiota product will be prepared from rigorously screened healthy donors under standardized conditions, with controlled storage and traceability. Participants will be assigned in a 1:1 ratio to the fecal microbiota transplantation group or the fecal microbiota transplantation plus prebiotic group, with 13 participants in each group. Participants in the combination group will receive additional dietary fiber prebiotic supplementation at a total dose of 24 g/day, administered as 12 g twice daily, starting on the day of fecal microbiota transplantation and continuing for 4 weeks.
Efficacy and safety will be systematically assessed during treatment and follow-up. Clinical assessments will include vital signs, mental status, West Haven grade, time to reversal of hepatic encephalopathy, recurrence of hepatic encephalopathy, hospitalization, and adverse events. Laboratory assessments will include complete blood count, liver function, renal function, coagulation function, plasma ammonia, hepatitis B virus DNA when applicable, alpha-fetoprotein, endotoxin, C-reactive protein, and interleukin-6. Liver disease severity will be assessed using Child-Pugh and MELD scores. Minimal hepatic encephalopathy testing and neurocognitive assessments will be performed when clinically feasible.
The primary efficacy endpoint is recurrence of hepatic encephalopathy, including recurrence rate, time to first recurrence, episode grade, episode duration, and the time from fecal microbiota transplantation to the first recurrence of hepatic encephalopathy. Secondary efficacy endpoints include changes in blood ammonia, liver function, renal function, inflammatory markers, liver function scores, psychological or neurocognitive test results, and gut microbiota diversity and taxonomic composition before and after fecal microbiota transplantation. Safety endpoints include overall adverse events, fecal microbiota transplantation-related adverse events, and serious adverse events, with particular attention to gastrointestinal symptoms, infection, worsening hepatic encephalopathy, hospitalization, septic shock, and death.
Participants will be followed at baseline before fecal microbiota transplantation, day 0 after completion of transplantation, day 15, month 1, month 3, and month 6. Additional assessments will be performed when hepatic encephalopathy occurs. At each scheduled time point, 5 mL of peripheral venous blood and 5 g of stool will be collected for laboratory testing and gut microbiota analysis. These data will be used to explore associations between microbial changes, clinical improvement, recurrence of hepatic encephalopathy, and safety outcomes.
Statistical analyses will be performed using the intention-to-treat principle. Clinical variables will be summarized using appropriate descriptive statistics and compared between groups when applicable. Time-dependent outcomes, including time to first recurrence and recurrence-free survival, will be analyzed using the Kaplan-Meier method and the Log-rank test. Competing risk models may be used to account for death or liver transplantation as competing events. Cox proportional hazards regression models will be used to explore factors associated with clinical outcomes. Microbiome data will be analyzed using diversity analysis, donor-recipient similarity assessment, changes in dominant bacterial taxa, and correlation or multivariable models to explore the relationship between gut microbiota dynamics and clinical outcomes.
225 studies on the registry are indexed under Hepatic Encephalopathy; 53 are open to participants now.
This study's planned enrollment of 26 is below the median of 60 across 154 interventional studies indexed under Hepatic Encephalopathy.
Browse Hepatic Encephalopathy studies →Air Force Military Medical University, China is the lead sponsor of 178 studies on the registry; 37 are open to participants now.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
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The New York Heart Association’s four classes of how much heart failure limits physical activity.
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GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CD4 count
The number of CD4 cells, a type of white blood cell, in a given amount of blood. It is used to follow how well the immune system is doing in HIV.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The fecal microbiota was transplanted via nasojejunal tube infusion. The infusion protocol was 100 mL per time, twice a day, for three consecutive days. The donor was strictly screened for infectious diseases and fecal pathogenic microorganisms, and was free of pathogenic bacteria and rich in beneficial bacteria such as Lachnospiraceae, Ruminococcaceae and Bifidobacteriaceae. The fecal microbiota preparation was prepared under sterile conditions and stored in a standardized manner.
Biological: Fecal Microbiota Transplantation · Drug: Rifaximin、Lactulose
Participants in this arm received the same fecal microbiota transplantation protocol as the fecal microbiota transplantation group. The fecal microbiota was transplanted via nasojejunal tube infusion at a dose of 100 mL per administration, twice daily, for three consecutive days. The donor was strictly screened for infectious diseases and fecal pathogenic microorganisms, and the fecal microbiota preparation was prepared under sterile conditions and stored in a standardized manner. In addition to fecal microbiota transplantation, participants received dietary fiber prebiotic supplementation at a total dose of 24 g per day, administered as 12 g twice daily, starting on the day of fecal microbiota transplantation and continuing for four weeks. All participants continued standard medical therapy with rifaximin and lactulose during the study period.
Biological: Fecal Microbiota Transplantation · Drug: Rifaximin、Lactulose · Dietary Supplement: Dietary Fiber Prebiotic
Fecal microbiota transplantation is used to reconstruct gut microbiota structure, regulate intestinal microecological homeostasis, improve intestinal barrier function, reduce systemic endotoxin load and inflammatory level, for the prevention and treatment of refractory hepatic encephalopathy after TIPS. The preparation is made from stool of qualified screened donors, processed under sterile conditions.
Also known as: FMT
Rifaximin is a non-absorbable oral rifamycin antibiotic, used as standard medical therapy for hepatic encephalopathy, to reduce intestinal urease-producing bacteria and intestinal ammonia production.Lactulose is a synthetic disaccharide laxative, used as first-line standard medical therapy for hepatic encephalopathy, to acidify the intestinal lumen, reduce ammonia production and promote ammonia excretion.
Participants assigned to the FMT plus prebiotic group will receive dietary fiber prebiotic supplementation in addition to fecal microbiota transplantation and standard medical therapy. The prebiotic will be administered at a total dose of 24 g per day, given as 12 g twice daily, starting on the day of fecal microbiota transplantation and continuing for four weeks. Standard medical therapy with rifaximin and lactulose will be continued during the study period.
Incidence and severity of treatment-related adverse events (AEs) and serious adverse events (SAEs)
Record the number, incidence, severity (graded by NCI-CTC v3.0 criteria), correlation with trial intervention, and outcome of all AEs, FMT-related AEs and SAEs in subjects from randomization to the end of follow-up. Key monitoring includes gastrointestinal reactions, infection, exacerbation of hepatic encephalopathy and other intervention-related adverse events.
Time frame: From the date of randomization to the end of 6-month follow-up after intervention
Reversal time of hepatic encephalopathy
The reversal time of hepatic encephalopathy is defined as the time required from the start of fecal microbiota transplantation treatment until the patient's clinical consciousness state recovers to the remission state of hepatic encephalopathy. Hepatic encephalopathy remission is defined as a significant improvement in the West Haven classification compared to the baseline and a return to grade 0-1, with significant relief of related neurological and mental symptoms. The reversal time is recorded in hours or days and is used to assess the speed of improvement in hepatic encephalopathy after treatment.
Time frame: Throughout the entire period from the end of the intervention to 6 months after the intervention
Recurrent rate of hepatic encephalopathy
The recurrent rate of hepatic encephalopathy is defined as the proportion of subjects who experienced overt hepatic encephalopathy again during the follow-up period after receiving fecal microbiota transplantation treatment. Overt hepatic encephalopathy is evaluated according to the West Haven classification, and is defined as a hepatic encephalopathy event with a West Haven grade of ≥2. During the study period, the time of the first recurrence, the number of recurrences, and the severity of recurrence of the subjects were recorded, and the recurrence rates at each follow-up time point and throughout the entire follow-up period were calculated.
Time frame: Throughout the entire period from the end of the intervention to 6 months after the intervention
The colonization status of the intestinal microbiota
The survival rate (%) of the donor microbiota in the patient's intestinal tract
Time frame: Baseline, 15 days after intervention, 1 month after intervention, 3 months after intervention, 6 months after intervention
Changes in the α diversity of the intestinal microbiota
Using metagenomic sequencing technology, the α diversity of the intestinal microbiota (Shannon index, Simpson index) was evaluated.
Time frame: Baseline, 15 days after intervention, 1 month after intervention, 3 months after intervention, 6 months after intervention
Started Jun 2026 (actual). Primary completion is estimated for Jan 2027, 7 months after the start.
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