Evaluation of the Outcome of Fecal Microbiota Transplantation

NCT07454408 | Not Yet Recruiting Phase 1

• 1 other identifier: TIPS-HE-FMT
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a randomized, placebo-controlled, exploratory phase II clinical trial led by Professor Han Gyeong-ho from the Digestive Disease Hospital of Xi'an International Medical Center. The study enrolled 40 patients who had experienced recurrence of hepatic encephalopathy despite treatment with rifaximin and lactulose. These patients were randomly divided 1:1 into the experimental group and the control group. After obtaining informed consent from the patients, fecal microbiota transplantation or placebo control was performed. The fecal microbiota was sourced from the feces of healthy individuals who had a rich composition of the Muribaculaceae, Ruminococcaceae, and Bifidobacteriaceae families and did not contain pathogenic bacteria. The safety and efficacy of the treatment were followed up, and blood and fecal samples were collected for sequencing analysis. The aim was to provide new solutions for patients with hepatic encephalopathy who did not respond to the treatment with rifaximin and lactulose after TIPS surgery; and to explore the impact of microbiota changes and translocation on the recurrence of hepatic encephalopathy after TIPS surgery.

Conditions

Hepatic Encephalopathy; Fecal Microbiota Transplantation; TIPS

Keywords

Hepatic Encephalopathy; Fecal Microbiota Transplantation; TIPS; FMT

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)

• The recurrence rate of hepatic encephalopathy fecal microbiota transplantation intervention

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

• The changes in health-related quality of life after fecal microbiota transplantation intervention

  Baseline, 1 month after intervention, 3 months after intervention, 6 months after 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 Group

EXPERIMENTAL

All the subjects in this arm continued to receive standard medical treatment for hepatic encephalopathy: rifaximin 0.2g per tablet, 2 tablets per dose, 3 times a day, with a total daily dose of 1200mg; lactulose oral solution 25ml per dose, 2 times a day, with the dosage adjusted as needed according to clinical requirements. On the basis of the standard treatment, the subjects received intranasal jejunal tube infusion of fecal suspension (100mL per dose, 2 times a day, for 3 consecutive days), followed by oral enteric-coated freeze-dried fecal capsules (7 capsules per day, for 1 week). The fecal preparation was prepared under sterile conditions. The donor feces used were all subjected to strict screening for infectious diseases and pathogenicity and were rich in Clostridium mucosum, Rumenoccus, and Bifidobacterium.

Biological: Fecal Microbiota Transplantation; Drug: Rifaximin、Lactulose

Placebo Control Group

PLACEBO COMPARATOR

All subjects in this arm will receive the exact same standard medical therapy as the FMT group: rifaximin 0.2g tablets, 2 tablets each time, 3 times daily (total 1200mg per day); lactulose oral solution 25ml each time, twice daily, with dose adjusted according to clinical needs. On top of standard therapy, subjects will receive isovolumetric placebo solution via nasojejunal tube infusion (same frequency and duration as the FMT group), followed by matched oral placebo capsules (same dosage, frequency and duration as the FMT group). Placebo preparations are identical to FMT preparations in appearance, dosage form and administration route.

Other: FMT Matched Placebo; Drug: Rifaximin、Lactulose

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 Group

FMT Matched Placebo OTHER

Placebo preparation is identical to fecal microbiota transplantation preparation in appearance, dosage form, administration route and frequency, with no active biological or therapeutic components, used for the control arm of this randomized controlled trial.

Also known as: Placebo

Placebo Control 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 Group; Placebo Control 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:

• Aged between 18 and 75 years old
• Patients with recurrent hepatic encephalopathy (HE) after transjugular intrahepatic portosystemic shunt (TIPS), despite treatment with lactulose and rifaximin (at least 2 episodes of West Haven grade ≥2 HE within 6 months under lactulose and rifaximin intervention)
• Provided written informed consent from the patient

You may not qualify if:

• Malignant tumors of the liver, gastrointestinal tract or other systems
• Uncontrolled severe active infection (\>grade 2) or sepsis
• Spontaneous bacterial peritonitis
• Complicated with severe cardiac, renal or pulmonary insufficiency
• Other neuropsychiatric diseases, including dementia
• Budd-Chiari syndrome
• Alcohol dependence or use of psychotropic drugs (benzodiazepines, opioids, etc.)
• History of gastrointestinal surgery (e.g., colectomy) within 3 months before enrollment
• Pregnant or lactating subjects
• Poor compliance judged by the investigator
• Model for End-Stage Liver Disease (MELD) score \>17
• Tumor, immunodeficiency, or receiving immunosuppressive therapy within 3 months before enrollment
• Patients who have used other prebiotics, probiotics or fecal microbiota transplantation (FMT) before enrollment

Sponsors & Collaborators

• Air Force Military Medical University, China: lead

Study Sites (1)

Xi'an International Medical Center Hospital

Xi’an, Shanxi, 710100, China

Location

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 Jan 28. doi: 10.1038/s41591-025-04189-2. Online ahead of print.

  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 Jan 28. doi: 10.1038/s41591-025-04186-5. Online ahead of print.

  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 Jan 28. doi: 10.1038/s41591-025-04183-8. Online ahead of print.

  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

• Menghao LI

  Xi'an International Medical Center Hospital

  STUDY DIRECTOR

• Heng ZENG

  Xi'an International Medical Center Hospital

  STUDY DIRECTOR

• Xing WANG

  Xi'an International Medical Center Hospital

  STUDY DIRECTOR

• Gui ZHANG

  Xi'an International Medical Center Hospital

  STUDY DIRECTOR

• Zhanxin YIN

  Xi'an International Medical Center Hospital

  STUDY DIRECTOR

• Ruijun LI

  Xi'an International Medical Center Hospital

  STUDY DIRECTOR

• Wei BAI

  Xi'an International Medical Center Hospital

  STUDY DIRECTOR

• Dongdong XIA

  Xi'an International Medical Center Hospital

  STUDY DIRECTOR

• Na ZHANG

  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

• Feifei WU

  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: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This trial adopts a double-blind design for participants and investigators. FMT preparations (nasojejunal infusion solution + enteric-coated capsules) and matched placebo are identical in appearance, dosage form, administration route, frequency and course. Preparations are coded by independent researchers not involved in trial implementation. All participants, investigators, outcome assessors and statisticians will remain blinded to group allocation. The randomization code will be unblinded only after all clinical data are locked, with an emergency unblinding mechanism for serious adverse events.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: This is a single-center, randomized, placebo-controlled, exploratory phase II clinical trial. A total of 40 eligible patients aged 18-75 years with drug-refractory hepatic encephalopathy (HE) after TIPS (≥2 episodes of West Haven ≥2 grade HE within 6 months despite lactulose and rifaximin treatment) will be enrolled. Subjects will be 1:1 randomly assigned to the FMT group or placebo group. Both groups will receive standard HE therapy (rifaximin + lactulose). The FMT group will receive FMT via nasojejunal infusion plus oral capsules, while the control group will receive matched placebo with the same administration regimen. All subjects will be followed up for 6 months to evaluate the safety and efficacy of FMT.

Study Record Dates

• First Submitted: March 2, 2026
• First Posted: March 6, 2026
• Study Start: March 7, 2026
• Primary Completion (Estimated): June 6, 2028
• Study Completion (Estimated): June 30, 2028
• Last Updated: March 6, 2026

Record last verified: 2026-03

Locations

CN (1)