Evaluation of the Outcome of Fecal Microbiota Transplantation

Официальное название

A Clinical Randomized Controlled Study on the Prevention and Treatment of Drug-refractory Hepatic Encephalopathy After TIPS With Fecal Microbiota Transplantation

Обзор

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.

Подробное описание

This study is a single-center, randomized, placebo-controlled, exploratory phase II clinical trial. A total of 40 patients aged 18-75 years who had drug-refractory hepatic encephalopathy after transjugular intrahepatic portosystemic shunt surgery and experienced at least 2 West Haven grade ≥2 hepatic encephalopathy episodes within 6 months of treatment with lactulose and rifaximin were planned to be enrolled: These patients were randomly assigned in a 1:1 ratio to the fecal microbiota transplantation group and the placebo group. Both groups received basic standard treatment: 1200mg/day of rifaximin + 25ml/once of lactulose, twice/day; The FMT group was additionally infused with fecal suspension (100mL/once, twice/day, for 3 consecutive days) through the nasal jejunostomy tube combined with oral enteric-coated freeze-dried fecal capsules (7 capsules each time, for 1 week), while the placebo group was given the same volume of placebo solution and placebo capsules, with the same frequency and duration as the FMT group. All subjects were followed up at 15 days, 1 month, 3 months, and 6 months after transplantation. The primary outcomes were the safety (adverse events, severe adverse events, FMT-related adverse events) and efficacy (hepatic encephalopathy recurrence rate, time to first recurrence, West Haven classification) of FMT; The secondary outcomes were changes in intestinal flora colonization and diversity, liver function, blood ammonia levels, and health-related quality of life (CLDQ scale). Fecal and blood samples were collected at each follow-up time point for multi-omics detection and analysis. Statistical analysis of the trial data was performed using Kaplan-Meier method, Log-rank test, and Cox proportional hazards regression model.

Вмешательства

• Биопрепарат Fecal Microbiota Transplantation
  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.
• Другое FMT Matched Placebo
  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.
• Препарат Rifaximin、Lactulose
  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.

Первичные конечные точки

• Incidence and severity of treatment-related adverse events (AEs) and serious adverse events (SAEs) [Срок оценки: From the date of randomization to the end of 6-month follow-up after intervention]

Вторичные конечные точки (4)

• The recurrence rate of hepatic encephalopathy fecal microbiota transplantation intervention [Срок оценки: 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 [Срок оценки: Baseline, 1 month after intervention, 3 months after intervention, 6 months after intervention]
• The colonization status of the intestinal microbiota [Срок оценки: 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 [Срок оценки: Baseline, 15 days after intervention, 1 month after intervention, 3 months after intervention, 6 months after intervention]

Критерии участия

Критерии включения

• Aged between 18 and 75 years old
• Patients who have experienced esophageal-gastric variceal bleeding or recurrent refractory ascites and meet the inclusion criteria, and for whom conservative treatment has failed, are planned to undergo elective TIPS surgery
• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Профилактика

Центры проведения

Китай · 1 центр

• Xi'an International Medical Center Hospital — Xi’an

Публикации

• 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
• 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 3 PMID 28586116
• 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
• 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 PMID 41606119
• 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 D PMID 41606121
• 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
• 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
• 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

Идентификаторы

NCT: NCT07454408 · TIPS-HE-FMT

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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