Hepatic EncephalopathyEarly Phase 1NCT07683936
Fecal Microbiota Transplantation for the Treatment of Refractory Hepatic Encephalopathy After TIPS Surgery
A Early Phase 1 study testing Fecal Microbiota Transplantation, Rifaximin、Lactulose and Dietary Fiber Prebiotic in people with Hepatic Encephalopathy and Fecal Microbiota Transplantation, run by Air Force Military Medical University, China at 1 site in China.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatic Encephalopathy, Fecal Microbiota Transplantation, TIPS
- What is being tested?
- Fecal Microbiota Transplantation, Rifaximin、Lactulose and Dietary Fiber Prebiotic
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteChina
- Study dates
- 1 Jun 2026to 1 Jun 2028
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age: 18 - 75 years old, both genders are eligible
- Successful implementation of covered stent TIPS
- Those who experienced recurrence of hepatic encephalopathy after TIPS surgery and still used lactulose and rifaximin (within 6 months after intervention with rifaximin and lactulose, West Haven grade ≥ 2 hepatic encephalopathy occurred at least 2 times)
- Meet the conditions for receiving fecal microbiota transplantation through nasogastric tube (no severe anatomical abnormalities in the upper digestive tract; basic intestinal motility is normal; can tolerate the insertion of nasogastric tube and the subsequent infusion process)
- Obtain the patient's written informed consent
Who cannot join
- Patients with active gastrointestinal bleeding or perforation accompanied by severe damage to the intestinal barrier due to various reasons
- Patients with congenital or acquired immunodeficiency diseases, those who have received high-risk immunosuppressive or cytotoxic drug treatment within the recent 3 months, and those with severe immunosuppression (neutrophil count < 1.5×10⁶ cells/L; CD4+ T cell count < 2.0×10⁵ cells/L)
- Patients with malignant tumors of the liver or gastrointestinal tract, patients with spontaneous bacterial peritonitis, and patients with Budd-Chiari syndrome
- Patients with severe heart, kidney, or lung dysfunction (NYHA III-IV grade or unstable heart failure; eGFR < 30 ml/min/1.73m² or requiring dialysis; respiratory failure or requiring long-term oxygen therapy)
- Unstable vital signs (body temperature, heart rate, blood pressure, breathing)
- History of gastrointestinal surgery within the past 3 months, such as colon resection
Show all 12Show fewer
- Patients planning to undergo liver transplantation within 6 months
- Patients who have undergone FMT within the past 3 months
- Alcohol dependence or use of psychotropic drugs (benzodiazepines, opioids, etc.)
- Other neurological and psychiatric disorders, including dementia, Parkinson's disease, and post-stroke sequelae
- Pregnant or lactating subjects
- Subjects considered to have poor compliance by the investigator
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Xi'an International Medical Center Hospital
Xi'an
Guohong HAN, Professor, 13991969930, 13991969930@126.com
About this study
Official title: A Prospective Exploratory Study on Fecal Microbiota Transplantation for the Treatment of Refractory Hepatic Encephalopathy After TIPS Surgery
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.
Read the detailed description
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.
- Conditions
- Hepatic Encephalopathy, Fecal Microbiota Transplantation, TIPS, Refractory Hepatic Encephalopathy
- Being tested
- Fecal Microbiota Transplantation, Rifaximin、Lactulose, Dietary Fiber Prebiotic
- Keywords
- Hepatic Encephalopathy, Fecal Microbiota Transplantation, TIPS, Refractory Hepatic Encephalopathy
- Medical subject headings
- Hepatic Encephalopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fecal Microbiota TransplantationBiological
Also called FMT
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.
Rifaximin、LactuloseDrug
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.
Dietary Fiber PrebioticDietary supplement
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.
| Study group | Role | What they receive |
|---|---|---|
| Fecal Microbiota Transplantation | Experimental | 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. Receives: Biological: Fecal Microbiota Transplantation; Drug: Rifaximin、Lactulose |
| Fecal Microbiota Transplantation plus Prebiotic Group | Experimental | 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. Receives: Biological: Fecal Microbiota Transplantation; Drug: Rifaximin、Lactulose; Dietary Supplement: Dietary Fiber Prebiotic |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From the date of randomization to the end of 6-month follow-up after intervention
Secondary outcomes (4)
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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: Baseline, 15 days after intervention, 1 month after intervention, 3 months after intervention, 6 months after intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jul 2026
- Study start1 Jun 2026
- Primary completion31 Jan 2027 (estimated)
- Study completion1 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Hepatic EncephalopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 26 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Air Force Military Medical University, China
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Guohong Han, Air Force Military Medical University, China
- Investigators
- Guohong HAN, Professor, Study chair, Xi'an International Medical Center HospitalGuohong HAN, Professor, Principal investigator, Xi'an International Medical Center HospitalMingtao ZHAO, Study director, Xi'an Jiaotong UniversityHeng ZENG, Study director, Xi'an International Medical Center HospitalNa ZHANG, Study director, Xi'an International Medical Center HospitalYiwei SHANG, Study director, Xi'an International Medical Center HospitalJing LI, Study director, Xi'an International Medical Center HospitalZhengyu WANG, Study director, Xi'an International Medical Center Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07683936
- Sponsor's protocol ID
- TIPS-HE-FMT002
- Status last verified
- Jun 2026
- First submitted
- 29 Jun 2026
- Last updated
- 6 Jul 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Bajaj JS, Fagan A, Gavis EA, Sterling RK, Gallagher ML, Lee H, Matherly SC, Siddiqui MS, Bartels A, Mousel T, Davis BC, Puri P, Fuchs M, Moutsoglou DM, Thacker LR, Sikaroodi M, Gillevet PM, Khoruts A. Microbiota transplant for hepatic encephalopathy in cirrhosis: The THEMATIC trial. J Hepatol. 2025 Jul;83(1):81-91. doi: 10.1016/j.jhep.2024.12.047. Epub 2025 Jan 10.
PubMed 39800192Bajaj JS, Kassam Z, Fagan A, Gavis EA, Liu E, Cox IJ, Kheradman R, Heuman D, Wang J, Gurry T, Williams R, Sikaroodi M, Fuchs M, Alm E, John B, Thacker LR, Riva A, Smith M, Taylor-Robinson SD, Gillevet PM. Fecal microbiota transplant from a rational stool donor improves hepatic encephalopathy: A randomized clinical trial. Hepatology. 2017 Dec;66(6):1727-1738. doi: 10.1002/hep.29306. Epub 2017 Oct 30.
PubMed 28586116Bajaj 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.
PubMed 31038755Porcari S, Ciccarese C, Heidrich V, Rondinella D, Quaranta G, Severino A, Arduini D, Buti S, Fornarini G, Primi F, Stumbo L, Giannarelli D, Giudice GC, Damassi A, Giron Berrios JR, Puncochar M, Barbazuk TB, Piccinno G, Pinto F, Armanini F, Asnicar F, Schinzari G, Derosa L, Kroemer G, Sanguinetti M, Masucci L, Gasbarrini A, Tortora G, Cammarota G, Zitvogel L, Segata N, Iacovelli R, Ianiro G. Fecal microbiota transplantation plus pembrolizumab and axitinib in metastatic renal cell carcinoma: the randomized phase 2 TACITO trial. Nat Med. 2026 Apr;32(4):1316-1324. doi: 10.1038/s41591-025-04189-2. Epub 2026 Jan 28.
PubMed 41606119Duttagupta S, Messaoudene M, Hunter S, Desilets A, Jamal R, Mihalcioiu C, Belkaid W, Marcoux N, Fidelle M, Suissa D, Ponce M, Geiger M, Malo J, Piccinno G, Puncochar M, Filin A, Heidrich V, Rusu D, Mbaye B, Durand S, Ben Aissa I, Puller V, de Lahondes R, Blais N, Tehfe M, Owen S, Belanger K, Parvathy SN, Shieh B, Raphael J, Lenehan J, Breadner D, Rothenstein J, Rozza N, Maillou J, Nili S, Prifti DK, Pinto F, Armanini F, Kim-Schulze S, Marron TU, Kroemer G, Derosa L, Zitvogel L, Silverman M, Segata N, Maleki Vareki S, Routy B, Elkrief A. Fecal microbiota transplantation plus immunotherapy in non-small cell lung cancer and melanoma: the phase 2 FMT-LUMINate trial. Nat Med. 2026 Apr;32(4):1337-1350. doi: 10.1038/s41591-025-04186-5. Epub 2026 Jan 28.
PubMed 41606121Fernandes R, Jabbarizadeh B, Rajeh A, Hong MMY, Baines KJ, Ernst S, Winquist E, Ali AS, Penny S, Figueredo R, Parvathy SN, Lenehan JG, Pinto DM, Silverman MS, Maleki Vareki S. Fecal microbiota transplantation plus immunotherapy in metastatic renal cell carcinoma: the phase 1 PERFORM trial. Nat Med. 2026 Apr;32(4):1325-1336. doi: 10.1038/s41591-025-04183-8. Epub 2026 Jan 28.
PubMed 41606120Bloom PP, Donlan J, Torres Soto M, Daidone M, Hohmann E, Chung RT. Fecal microbiota transplant improves cognition in hepatic encephalopathy and its effect varies by donor and recipient. Hepatol Commun. 2022 Aug;6(8):2079-2089. doi: 10.1002/hep4.1950. Epub 2022 Apr 5.
PubMed 35384391Quan X, Li Y, Wu H. Reply to "Probiotics for Hepatic Encephalopathy Prevention After TIPS: Still an Open Question". Liver Int. 2025 Nov;45(11):e70383. doi: 10.1111/liv.70383. No abstract available.
PubMed 41047753Li M, Li K, Tang S, Lv Y, Wang Q, Wang Z, Luo B, Niu J, Zhu Y, Guo W, Bai W, Wang E, Xia D, Wang Z, Li X, Yuan J, Yin Z, Trebicka J, Han G. Restoration of the gut microbiota is associated with a decreased risk of hepatic encephalopathy after TIPS. JHEP Rep. 2022 Feb 15;4(5):100448. doi: 10.1016/j.jhepr.2022.100448. eCollection 2022 May.
PubMed 35313729
Study at a glance
From the registry record, last updated by the sponsor on 6 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Exploratory Study on Fecal Microbiota Transplantation for the Treatment of Refractory Hepatic Encephalopathy After TIPS Surgery
- ClinicalTrials.gov ID
- NCT07683936
- Acronym / sponsor ID
- TIPS-HE-FMT002
- Conditions
- Hepatic Encephalopathy, Fecal Microbiota Transplantation, TIPS, Refractory Hepatic Encephalopathy
- Keywords
- Hepatic Encephalopathy, Fecal Microbiota Transplantation, TIPS, Refractory Hepatic Encephalopathy
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 26 participants (estimated)
- Lead sponsor
- Air Force Military Medical University, ChinaUniversity, hospital or other
- Study start
- 1 Jun 2026 (actual)
- Primary completion
- 31 Jan 2027 (estimated)
- Study completion
- 1 Jun 2028 (estimated)
- First posted
- 6 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fecal Microbiota Transplantation | Experimental | Biological: Fecal Microbiota Transplantation, Drug: Rifaximin、LactuloseThe 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. |
| Fecal Microbiota Transplantation plus Prebiotic Group | Experimental | Biological: Fecal Microbiota Transplantation, Drug: Rifaximin、Lactulose, Dietary Supplement: Dietary Fiber PrebioticParticipants 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age: 18 - 75 years old, both genders are eligible
- Successful implementation of covered stent TIPS
- Those who experienced recurrence of hepatic encephalopathy after TIPS surgery and still used lactulose and rifaximin (within 6 months after intervention with rifaximin and lactulose, West Haven grade ≥ 2 hepatic encephalopathy occurred at least 2 times)
- Meet the conditions for receiving fecal microbiota transplantation through nasogastric tube (no severe anatomical abnormalities in the upper digestive tract; basic intestinal motility is normal; can tolerate the insertion of nasogastric tube and the subsequent infusion process)
- Obtain the patient's written informed consent
Key exclusion criteria (12 listed)
- Patients with active gastrointestinal bleeding or perforation accompanied by severe damage to the intestinal barrier due to various reasons
- Patients with congenital or acquired immunodeficiency diseases, those who have received high-risk immunosuppressive or cytotoxic drug treatment within the recent 3 months, and those with severe immunosuppression (neutrophil count < 1.5×10⁶ cells/L; CD4+ T cell count < 2.0×10⁵ cells/L)
- Patients with malignant tumors of the liver or gastrointestinal tract, patients with spontaneous bacterial peritonitis, and patients with Budd-Chiari syndrome
- Patients with severe heart, kidney, or lung dysfunction (NYHA III-IV grade or unstable heart failure; eGFR < 30 ml/min/1.73m² or requiring dialysis; respiratory failure or requiring long-term oxygen therapy)
- Unstable vital signs (body temperature, heart rate, blood pressure, breathing)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fecal Microbiota TransplantationAlso: FMTFecal 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. | Biological | Fecal Microbiota Transplantation, Fecal Microbiota Transplantation plus Prebiotic Group |
| Rifaximin、LactuloseRifaximin 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. | Drug | Fecal Microbiota Transplantation, Fecal Microbiota Transplantation plus Prebiotic Group |
| Dietary Fiber PrebioticParticipants 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. | Dietary supplement | Fecal Microbiota Transplantation plus Prebiotic Group |
Primary outcome
Incidence and severity of treatment-related adverse events (AEs) and serious adverse events (SAEs)
Time frame: From the date of randomization to the end of 6-month follow-up after intervention
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.
4 secondary outcomes
Reversal time of hepatic encephalopathy
Time frame: Throughout the entire period from the end of the intervention to 6 months after the intervention
Recurrent rate of hepatic encephalopathy
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
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
Time frame: Baseline, 15 days after intervention, 1 month after intervention, 3 months after intervention, 6 months after intervention
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jul 2026.
- Background: PubMed 39800192Bajaj JS, Fagan A, Gavis EA, Sterling RK, Gallagher ML, Lee H, Matherly SC, Siddiqui MS, Bartels A, Mousel T, Davis BC, Puri P, Fuchs M, Moutsoglou DM, Thacker LR, Sikaroodi M, Gillevet PM, Khoruts A. Microbiota transplant for hepatic encephalopathy in cirrhosis: The THEMATIC trial. J Hepatol. 2025 Jul;83(1):81-91. doi: 10.1016/j.jhep.2024.12.047. Epub 2025 Jan 10.
- Background: PubMed 28586116Bajaj JS, Kassam Z, Fagan A, Gavis EA, Liu E, Cox IJ, Kheradman R, Heuman D, Wang J, Gurry T, Williams R, Sikaroodi M, Fuchs M, Alm E, John B, Thacker LR, Riva A, Smith M, Taylor-Robinson SD, Gillevet PM. Fecal microbiota transplant from a rational stool donor improves hepatic encephalopathy: A randomized clinical trial. Hepatology. 2017 Dec;66(6):1727-1738. doi: 10.1002/hep.29306. Epub 2017 Oct 30.
- Background: PubMed 31038755Bajaj 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.
- Background: PubMed 41606119Porcari S, Ciccarese C, Heidrich V, Rondinella D, Quaranta G, Severino A, Arduini D, Buti S, Fornarini G, Primi F, Stumbo L, Giannarelli D, Giudice GC, Damassi A, Giron Berrios JR, Puncochar M, Barbazuk TB, Piccinno G, Pinto F, Armanini F, Asnicar F, Schinzari G, Derosa L, Kroemer G, Sanguinetti M, Masucci L, Gasbarrini A, Tortora G, Cammarota G, Zitvogel L, Segata N, Iacovelli R, Ianiro G. Fecal microbiota transplantation plus pembrolizumab and axitinib in metastatic renal cell carcinoma: the randomized phase 2 TACITO trial. Nat Med. 2026 Apr;32(4):1316-1324. doi: 10.1038/s41591-025-04189-2. Epub 2026 Jan 28.
- Background: PubMed 41606121Duttagupta S, Messaoudene M, Hunter S, Desilets A, Jamal R, Mihalcioiu C, Belkaid W, Marcoux N, Fidelle M, Suissa D, Ponce M, Geiger M, Malo J, Piccinno G, Puncochar M, Filin A, Heidrich V, Rusu D, Mbaye B, Durand S, Ben Aissa I, Puller V, de Lahondes R, Blais N, Tehfe M, Owen S, Belanger K, Parvathy SN, Shieh B, Raphael J, Lenehan J, Breadner D, Rothenstein J, Rozza N, Maillou J, Nili S, Prifti DK, Pinto F, Armanini F, Kim-Schulze S, Marron TU, Kroemer G, Derosa L, Zitvogel L, Silverman M, Segata N, Maleki Vareki S, Routy B, Elkrief A. Fecal microbiota transplantation plus immunotherapy in non-small cell lung cancer and melanoma: the phase 2 FMT-LUMINate trial. Nat Med. 2026 Apr;32(4):1337-1350. doi: 10.1038/s41591-025-04186-5. Epub 2026 Jan 28.
- Background: PubMed 41606120Fernandes R, Jabbarizadeh B, Rajeh A, Hong MMY, Baines KJ, Ernst S, Winquist E, Ali AS, Penny S, Figueredo R, Parvathy SN, Lenehan JG, Pinto DM, Silverman MS, Maleki Vareki S. Fecal microbiota transplantation plus immunotherapy in metastatic renal cell carcinoma: the phase 1 PERFORM trial. Nat Med. 2026 Apr;32(4):1325-1336. doi: 10.1038/s41591-025-04183-8. Epub 2026 Jan 28.
- Background: PubMed 35384391Bloom PP, Donlan J, Torres Soto M, Daidone M, Hohmann E, Chung RT. Fecal microbiota transplant improves cognition in hepatic encephalopathy and its effect varies by donor and recipient. Hepatol Commun. 2022 Aug;6(8):2079-2089. doi: 10.1002/hep4.1950. Epub 2022 Apr 5.
- Background: PubMed 41047753Quan X, Li Y, Wu H. Reply to "Probiotics for Hepatic Encephalopathy Prevention After TIPS: Still an Open Question". Liver Int. 2025 Nov;45(11):e70383. doi: 10.1111/liv.70383. No abstract available.
- Results publication: PubMed 35313729Li M, Li K, Tang S, Lv Y, Wang Q, Wang Z, Luo B, Niu J, Zhu Y, Guo W, Bai W, Wang E, Xia D, Wang Z, Li X, Yuan J, Yin Z, Trebicka J, Han G. Restoration of the gut microbiota is associated with a decreased risk of hepatic encephalopathy after TIPS. JHEP Rep. 2022 Feb 15;4(5):100448. doi: 10.1016/j.jhepr.2022.100448. eCollection 2022 May.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Guohong HAN, Professor study chair
Xi'an International Medical Center Hospital
Guohong HAN, Professor principal investigator
Xi'an International Medical Center Hospital
Mingtao ZHAO study director
Xi'an Jiaotong University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Fecal Microbiota Transplantation, Rifaximin、Lactulose and Dietary Fiber Prebiotic in people with Hepatic Encephalopathy and Fecal Microbiota Transplantation, run by Air Force Military Medical University, China at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 6 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Guohong HAN, Professor (13991969930, 13991969930@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence and severity of treatment-related adverse events (AEs) and serious adverse events (SAEs) (time frame: From the date of randomization to the end of 6-month follow-up after intervention). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07683936, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jul 2026.