Clinical trial NCT06368895: Fecal Microbiota Transplantation by Oral Capsules for Hepatic Encephalopathy Treatment
Official title: Efficacy and Safety of Fecal Microbiota Transplantation by Oral Capsules in Patients With Liver
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Hepatic Encephalopathy
Dysbiosis
Lead sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Sponsor class: OTHER
First posted: 2024-04-16
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This interventional study aims to evaluate the safety and efficacy of oral capsule fecal microbiota transplantation (FMT) for treating hepatic encephalopathy refractory to conventional rifaximin and lactulose therapy in patients with liver cirrhosis. Patients diagnosed with hepatic encephalopathy refractory to rifaximin and lactulose therapy will be randomized into three groups. While continuing conventional therapy, the first group receives FMT via colonoscopy and oral capsule administration, the second group receives only oral capsule administration, and the third group serves as a control, receiving only conventional therapy.

The aims of the study are:

To evaluate the efficacy and safety of FMT by oral capsules in cirrhotic patients with hepatic encephalopathy refractory to standard therapy.

To evaluate changes in the gut microbiota composition and in the intestinal and systemic inflammatory condition occurring after FMT and if they can be associated with clinical improvement.

To evaluate metabolic modifications occurring after FMT and if they can be associated with clinical improvement.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of liver cirrhosis
* Hepatic encephalopathy of grade \>1 or higher according to West Haven classification, persistent or recurrent despite treatment with lactulose/lactitol and rifaximin at adequate doses started at least 30 days before the Hepatic encephalopathy episode

Exclusion Criteria:

* Na \<130 meq /l
* Creatinine \> 1.3 mg / dl
* Presence of grade 3 ascites
* Presence of esophagogastric varices at risk of haemorrhage in the absence of adequate prophylaxis
* Presence of other possible causes of encephalopathy (cerebral vascular disease, known neurodegenerative or cognitive disorders)
* Known psychiatric disorders or other causes of brain dysfunction (e.g. hypoglycemia, hyponatremia)
* Alcohol consumption
* Diagnosis of hepatocellular carcinoma
* Contraindication to fecal microbiota transplantation (e.g. pregnancy or breastfeeding)
* Presence of known intestinal diseases
* Any clinical condition that, in the opinion of the investigators, may contraindicate the enrollment in the study

Primary outcomes:
measure: Evaluation of safety of fecal microbiota transplantation by oral capsules in the treatment of cirrhotic patients with hepatic encephalopathy refractory to conventional therapy
timeFrame: 12 months
measure: Evaluation of efficacy of fecal microbiota transplantation by oral capsules in the treatment of cirrhotic patients with hepatic encephalopathy refractory to conventional therapy
timeFrame: 12 months
Secondary outcomes:
measure: Evaluation of changes in the gut microbiota composition following the fecal microbiota transplantation
timeFrame: 12 months
measure: Evaluation of changes in the systemic inflammatory following the fecal microbiota transplantation
timeFrame: 12 months
measure: Evaluation of changes in the intestinal inflammatory following the fecal microbiota transplantation
timeFrame: 12 months
measure: Comparison between protein metabolites concentration (ppm) in serum, urine and feces before and after microbiota transplantation
timeFrame: 12 months
measure: Comparison between lipid metabolites concentration (ppm) in serum, urine and feces before and after microbiota transplantation
timeFrame: 12 months
measure: Comparison between carbohydrates metabolites concentration (ppm) in serum, urine and feces before and after microbiota transplantation
timeFrame: 12 months
Other outcomes:
Locations:
city: Rome
country: Italy
facility: Fondazione Policlinico Agostino Gemelli IRCCS
Study officials:
References:
citation: Grover VP, Tognarelli JM, Massie N, Crossey MM, Cook NA, Taylor-Robinson SD. The why and wherefore of hepatic encephalopathy. Int J Gen Med. 2015 Dec 16;8:381-90. doi: 10.2147/IJGM.S86854. eCollection 2015.
citation: American Association for the Study of Liver Diseases; European Association for the Study of the Liver. Hepatic encephalopathy in chronic liver disease: 2014 practice guideline by the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases. J Hepatol. 2014 Sep;61(3):642-59. doi: 10.1016/j.jhep.2014.05.042. Epub 2014 Jul 8. No abstract available.
citation: Bajaj JS, Hafeezullah M, Hoffmann RG, Saeian K. Minimal hepatic encephalopathy: a vehicle for accidents and traffic violations. Am J Gastroenterol. 2007 Sep;102(9):1903-9. doi: 10.1111/j.1572-0241.2007.01424.x. Epub 2007 Jul 19.
citation: Fujisaka S, Avila-Pacheco J, Soto M, Kostic A, Dreyfuss JM, Pan H, Ussar S, Altindis E, Li N, Bry L, Clish CB, Kahn CR. Diet, Genetics, and the Gut Microbiome Drive Dynamic Changes in Plasma Metabolites. Cell Rep. 2018 Mar 13;22(11):3072-3086. doi: 10.1016/j.celrep.2018.02.060.
citation: Bajaj JS. The role of microbiota in hepatic encephalopathy. Gut Microbes. 2014 May-Jun;5(3):397-403. doi: 10.4161/gmic.28684. Epub 2014 Apr 1.
citation: Claesson MJ, Clooney AG, O'Toole PW. A clinician's guide to microbiome analysis. Nat Rev Gastroenterol Hepatol. 2017 Oct;14(10):585-595. doi: 10.1038/nrgastro.2017.97. Epub 2017 Aug 9.
citation: Kelly CR, Kahn S, Kashyap P, Laine L, Rubin D, Atreja A, Moore T, Wu G. Update on Fecal Microbiota Transplantation 2015: Indications, Methodologies, Mechanisms, and Outlook. Gastroenterology. 2015 Jul;149(1):223-37. doi: 10.1053/j.gastro.2015.05.008. Epub 2015 May 15.