Fecal Microbiota Transplantation for the Treatment of Refractory Hepatic Encephalopathy After TIPS Surgery

NCT07683936 | Recruiting Early Phase 1

• 1 other identifier: TIPS-HE-FMT002
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Fecal Microbiota Transplantation; TIPS; Hepatic Encephalopathy; Refractory Hepatic Encephalopathy

Keywords

Hepatic Encephalopathy; Fecal Microbiota Transplantation; TIPS; Refractory Hepatic Encephalopathy

Outcome Measures

Primary Outcomes (1)

• 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.

  From the date of randomization to the end of 6-month follow-up after intervention

Secondary Outcomes (4)

• Reversal time of hepatic encephalopathy

  Throughout the entire period from the end of the intervention to 6 months after the intervention

• Recurrent rate of hepatic encephalopathy

  Throughout the entire period from the end of the intervention to 6 months after the intervention

• The colonization status of the intestinal microbiota

  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

  Baseline, 15 days after intervention, 1 month after intervention, 3 months after intervention, 6 months after intervention

Study Arms (2)

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.

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.

Biological: Fecal Microbiota Transplantation; Drug: Rifaximin、Lactulose; Dietary Supplement: Dietary Fiber Prebiotic

Interventions

Fecal Microbiota Transplantation BIOLOGICAL

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

Fecal Microbiota Transplantation; Fecal Microbiota Transplantation plus Prebiotic Group

Rifaximin、Lactulose DRUG

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.

Fecal Microbiota Transplantation; Fecal Microbiota Transplantation plus Prebiotic Group

Dietary Fiber Prebiotic DIETARY_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.

Fecal Microbiota Transplantation plus Prebiotic Group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Air Force Military Medical University, China: lead

Study Sites (1)

Xi'an International Medical Center Hospital

Xi'an, China

RECRUITING

Related Publications (9)

• 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.

  PMID: 39800192 BACKGROUND

• Bajaj 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.

  PMID: 28586116 BACKGROUND

• 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.

  PMID: 31038755 BACKGROUND

• Porcari 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.

  PMID: 41606119 BACKGROUND

• Duttagupta 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.

  PMID: 41606121 BACKGROUND

• Fernandes 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.

  PMID: 41606120 BACKGROUND

• Bloom 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.

  PMID: 35384391 BACKGROUND

• Quan 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.

  PMID: 41047753 BACKGROUND

• Li 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.

  PMID: 35313729 RESULT

MeSH Terms

Conditions

Hepatic Encephalopathy

Interventions

Fecal Microbiota Transplantation

Condition Hierarchy (Ancestors)

Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Study Officials

• Guohong HAN, Professor

  Xi'an International Medical Center Hospital

  STUDY CHAIR

• Guohong HAN, Professor

  Xi'an International Medical Center Hospital

  PRINCIPAL INVESTIGATOR

• Mingtao ZHAO

  Xi'an Jiaotong University

  STUDY DIRECTOR

• Heng ZENG

  Xi'an International Medical Center Hospital

  STUDY DIRECTOR

• Na ZHANG

  Xi'an International Medical Center Hospital

  STUDY DIRECTOR

• Yiwei SHANG

  Xi'an International Medical Center Hospital

  STUDY DIRECTOR

• Jing LI

  Xi'an International Medical Center Hospital

  STUDY DIRECTOR

• Zhengyu WANG

  Xi'an International Medical Center Hospital

  STUDY DIRECTOR

• Bohan LUO

  Xi'an International Medical Center Hospital

  STUDY DIRECTOR

Central Study Contacts

Guohong HAN, Professor

CONTACT

13991969930; 13991969930@126.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 29, 2026
• First Posted: July 6, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): June 1, 2028
• Last Updated: July 6, 2026

Record last verified: 2026-06

Locations

CN (1)