Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT06368895
Other study ID # 2188
Secondary ID
Status Recruiting
Phase Phase 1
First received
Last updated
Start date April 7, 2021
Est. completion date June 2025

Study information

Verified date April 2024
Source Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Recruiting
Enrollment 60
Est. completion date June 2025
Est. primary completion date June 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years to 80 Years
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Procedure:
Fecal microbiota transplantation delivery through colonoscopy
Patients will receive 4 L of macrogol and salts solution the afternoon before FMT and remain fasting the night before the scheduled treatment. During colonoscopy, about 350 mL of donor fecal preparation will be infused in the cecum.
Drug:
Fecal microbiota transplantation delivery through oral capsules
Intestinal gastro-resistant capsules (capacity 0.91 mL, overall 10^8-9 bacteria per capsule) will be filled with the fecal slurry. From each donation weighing 100 g, it is expected to obtain 150 cps, which will be promptly frozen and stored at -80°C. At each monthly visit, the patient will receive 60 capsules, to be stored at -20°C at home. Capsules will be administered orally at the dose of 1 cps twice a day from month 1 post-colonoscopy to patients in the FMT group 1 (colonoscopy plus capsules), and from day 1 to patients in the FMT group 2 (capsules only).

Locations

Country Name City State
Italy Fondazione Policlinico Agostino Gemelli IRCCS Rome

Sponsors (1)

Lead Sponsor Collaborator
Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Country where clinical trial is conducted

Italy, 

References & Publications (7)

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. Erratum In: J Hepatol. 2015 Oct;63(4):1055. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Evaluation of safety of fecal microbiota transplantation by oral capsules in the treatment of cirrhotic patients with hepatic encephalopathy refractory to conventional therapy Number of patients with treatment associated adverse events as assessed by CTCAE v5.0 12 months
Primary Evaluation of efficacy of fecal microbiota transplantation by oral capsules in the treatment of cirrhotic patients with hepatic encephalopathy refractory to conventional therapy Number of patients with an improvement or no worsening of hepatic encephalopathy after treatment administration as clinically assessed by West-Haven classification and psychometric tests (portosystemic hepatic encephalopathy syndrome test and inhibitory control test) and through laboratory measurement of ammonia serum levels. 12 months
Secondary Evaluation of changes in the gut microbiota composition following the fecal microbiota transplantation DNA and RNA microbiota sequencing on fecal samples will be performed every three months after treatment initiation to define changes in the abundance of bacteria and alpha diversity (by the Simpson's Index of Diversity). 12 months
Secondary Evaluation of changes in the systemic inflammatory following the fecal microbiota transplantation Changes in the systemic inflammatory condition will be assessed by the quantification of serum cytokines, chemokines, and bacterial fragments concentrations (units/ml): Interleukin1 beta, tumor necrosis factor alpha, Interleukin2, Interleukin6, Interleukin17, interferon gamma, Chemokine C-C motif ligand 2, Chemokine C-C motif ligand 3, Chemokine C-C motif ligand 4, Chemokine C-C motif ligand 5, Chemokine C-C motif ligand 10, Chemokine C-X-C motif ligand 10, lipopolysaccharides 12 months
Secondary Evaluation of changes in the intestinal inflammatory following the fecal microbiota transplantation Changes in the intestinal inflammatory condition will be assessed by the quantification of fecal calprotectin concentration (mg/dl). 12 months
Secondary Comparison between protein metabolites concentration (ppm) in serum, urine and feces before and after microbiota transplantation Quantification of amino acides will be performed before the microbiota transplantation and every three months after by the examination of serum, urine and fecal samples through liquid chromatography tandem mass spectrometry methods. 12 months
Secondary Comparison between lipid metabolites concentration (ppm) in serum, urine and feces before and after microbiota transplantation Quantification of fatty acids, acyl carnitine, tryglicerides, dyacil glycerols and phospholipides will be performed before the microbiota transplantation and every three months after by the examination of serum, urine and fecal samples through liquid chromatography tandem mass spectrometry methods. 12 months
Secondary Comparison between carbohydrates metabolites concentration (ppm) in serum, urine and feces before and after microbiota transplantation Quantification of tricarboxylic acid cycle compounds, sugars and sugar phosphates will be performed before the microbiota transplantation and every three months after by the examination of serum, urine and fecal samples through liquid chromatography tandem mass spectrometry methods. 12 months
See also
  Status Clinical Trial Phase
Completed NCT01559519 - Post Transjugular Intrahepatic Portosystemic Shunt (Tips) Albumine Infusion to Prevent Hepatic Encephalopathy Phase 4
Terminated NCT01846806 - The Role of Bacterial Overgrowth and Delayed Intestinal Transit in Hepatic Encephalopathy. N/A
Recruiting NCT01178372 - Secondary Prophylaxis of Hepatic Encephalopathy in Cirrhosis Phase 4
Completed NCT00740142 - Efficacy of Combined Oral L-ornithine-L-aspartate and Lactulose in Patients With Hepatic Encephalopathy Phase 4
Completed NCT00914056 - A Study of Controlled Lactulose Withdrawal N/A
Completed NCT00558038 - Safety and Efficacy of AST-120 Compared to Lactulose in Patients With Hepatic Encephalopathy Phase 2
Completed NCT00986895 - A Study of Glyceryl Tri-(4-phenylbutyrate) Administered Orally as a Single Dose, and Twice Daily for Seven Consecutive Days to Subjects With Hepatic Impairment With Cirrhosis and to a Control Group Phase 1
Completed NCT00287235 - Efficacy of Albumin Dialysis to Treat Patients With Hepatic Encephalopathy Using The Molecular Adsorbent Recirculating System (MARS) N/A
Recruiting NCT05539027 - Efficacy of L-Ornithine L-Aspartate (LOLA) as an Adjunct to Branched Chain Amino Acids (BCAA) Enriched Solutions on Clinical Outcomes in ICU Patients With Hepatic Encephalopathy Phase 4
Recruiting NCT04096014 - Late Evening and Early Morning Protein Supplement to Reduce Readmissions for Hepatic Encephalopathy N/A
Completed NCT05526404 - Prevention of Hepatic Encephalopathy With Mobile Application Based Lactulose Titration N/A
Completed NCT04082780 - Rifamycin in Minimal Hepatic Encephalopathy Phase 2
Enrolling by invitation NCT06367127 - Utility of the Clamping Bean Test (CBT) for Covert Hepatic Encephalopathy Screening
Active, not recruiting NCT05425316 - Speech in Hepatic Encephalopathy (HE)
Recruiting NCT04415294 - Flicker App for Minimal Hepatic Encephalopathy
Not yet recruiting NCT06072521 - Efficacy of Lactoferrin as an Adjunct Therapy in Patients With Hepatic Encephalopathy Phase 2
Completed NCT02636647 - Fecal Transplant in Recurrent Hepatic Encephalopathy Phase 1
Withdrawn NCT02086825 - A Randomized Comparison of Rifaximin Versus Lactulose in Hospitalized Cirrhotic Patients With Renal Failure Phase 3
Completed NCT01446523 - S. Endotoxin, Inflammatory Mediators and MRS Before and After Treatment in MHE N/A
Completed NCT01218568 - Rifaximin Plus Lactulose Versus Lactulose Alone for the Treatment of Hepatic Encephalopathy: a Double Blind Randomized Trial N/A