Hepatic EncephalopathyPhase 1NCT06368895
Fecal Microbiota Transplantation by Oral Capsules for Hepatic Encephalopathy Treatment
A Phase 1 study testing Fecal microbiota transplantation delivery through colonoscopy and Fecal microbiota transplantation delivery through oral capsules in people with Hepatic Encephalopathy and Dysbiosis, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Hepatic Encephalopathy, Dysbiosis
- What is being tested?
- Fecal microbiota transplantation delivery through colonoscopy and Fecal microbiota transplantation delivery through oral capsules
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteItaly
- Study dates
- 7 Apr 2021to 31 Oct 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Efficacy and Safety of Fecal Microbiota Transplantation by Oral Capsules in Patients With Liver
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:
Read more
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.
- Conditions
- Hepatic Encephalopathy, Dysbiosis
- Being tested
- Fecal microbiota transplantation delivery through colonoscopy, Fecal microbiota transplantation delivery through oral capsules
- Medical subject headings
- Hepatic Encephalopathy, Dysbiosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fecal microbiota transplantation delivery through colonoscopyProcedure or surgery
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.
Fecal microbiota transplantation delivery through oral capsulesDrug
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).
| Study group | Role | What they receive |
|---|---|---|
| Fecal microbiota transplantation through colonoscopy and oral capsules | Experimental | Patients with cirrhosis and hepatic encephalopathy refractory to conventional treatment will undergo a two-stage fecal microbiota transplantation: initial colonoscopic delivery followed by daily oral capsules administration one month later. Patients will continue also conventional therapy with rifaximin and lactulose Receives: Procedure: Fecal microbiota transplantation delivery through colonoscopy; Drug: Fecal microbiota transplantation delivery through oral capsules |
| Fecal microbiota transplantation through oral capsules | Experimental | Patients with cirrhosis and hepatic encephalopathy refractory to conventional treatment will undergo fecal microbiota transplantation through daily oral capsules administration. Patients will continue also conventional therapy with rifaximin and lactulose. Receives: Drug: Fecal microbiota transplantation delivery through oral capsules |
| Controls | No intervention | Patients with cirrhosis and hepatic encephalopathy refractory to conventional treatment will continue only conventional therapy with rifaximin and lactulose |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 12 months
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.
Measured: 12 months
Secondary outcomes (6)
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).
Measured: 12 months
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
Measured: 12 months
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).
Measured: 12 months
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.
Measured: 12 months
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.
Measured: 12 months
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.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Apr 2024
- Study start7 Apr 2021
- Primary completion14 Jun 2024
- Study completion31 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Hepatic EncephalopathyStudies of the same condition, open and under way.
- More trials run by Fondazione Policlinico Universitario Agostino Gemelli IRCCSThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06368895
- Sponsor's protocol ID
- 2188
- Status last verified
- Sep 2026
- First submitted
- 4 Apr 2024
- Last updated
- 18 Sep 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 26719720American 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.
PubMed 25015420Bajaj 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.
PubMed 17640323Fujisaka 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.
PubMed 29539432Bajaj 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.
PubMed 24690956Claesson 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.
PubMed 28790452Kelly 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.
PubMed 25982290
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Fecal Microbiota Transplantation by Oral Capsules in Patients With Liver
- ClinicalTrials.gov ID
- NCT06368895
- Acronym / sponsor ID
- 2188
- Conditions
- Hepatic Encephalopathy, Dysbiosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Fondazione Policlinico Universitario Agostino Gemelli IRCCSUniversity, hospital or other
- Study start
- 7 Apr 2021 (actual)
- Primary completion
- 14 Jun 2024 (actual)
- Study completion
- 31 Oct 2024 (actual)
- First posted
- 16 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Fecal microbiota transplantation through colonoscopy and oral capsules | Experimental | Procedure: Fecal microbiota transplantation delivery through colonoscopy, Drug: Fecal microbiota transplantation delivery through oral capsulesPatients with cirrhosis and hepatic encephalopathy refractory to conventional treatment will undergo a two-stage fecal microbiota transplantation: initial colonoscopic delivery followed by daily oral capsules administration one month later. Patients will continue also conventional therapy with rifaximin and lactulose |
| Fecal microbiota transplantation through oral capsules | Experimental | Drug: Fecal microbiota transplantation delivery through oral capsulesPatients with cirrhosis and hepatic encephalopathy refractory to conventional treatment will undergo fecal microbiota transplantation through daily oral capsules administration. Patients will continue also conventional therapy with rifaximin and lactulose. |
| Controls | No intervention | –Patients with cirrhosis and hepatic encephalopathy refractory to conventional treatment will continue only conventional therapy with rifaximin and lactulose |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (11 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fecal microbiota transplantation delivery through colonoscopyPatients 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. | Procedure or surgery | Fecal microbiota transplantation through colonoscopy and oral capsules |
| Fecal microbiota transplantation delivery through oral capsulesIntestinal 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). | Drug | Fecal microbiota transplantation through colonoscopy and oral capsules, Fecal microbiota transplantation through oral capsules |
Primary outcome
Evaluation of safety of fecal microbiota transplantation by oral capsules in the treatment of cirrhotic patients with hepatic encephalopathy refractory to conventional therapy
Time frame: 12 months
Number of patients with treatment associated adverse events as assessed by CTCAE v5.0
Evaluation of efficacy of fecal microbiota transplantation by oral capsules in the treatment of cirrhotic patients with hepatic encephalopathy refractory to conventional therapy
Time frame: 12 months
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.
6 secondary outcomes
Evaluation of changes in the gut microbiota composition following the fecal microbiota transplantation
Time frame: 12 months
Evaluation of changes in the systemic inflammatory following the fecal microbiota transplantation
Time frame: 12 months
Evaluation of changes in the intestinal inflammatory following the fecal microbiota transplantation
Time frame: 12 months
Comparison between protein metabolites concentration (ppm) in serum, urine and feces before and after microbiota transplantation
Time frame: 12 months
Comparison between lipid metabolites concentration (ppm) in serum, urine and feces before and after microbiota transplantation
Time frame: 12 months
Comparison between carbohydrates metabolites concentration (ppm) in serum, urine and feces before and after microbiota transplantation
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2026.
- Background: PubMed 26719720Grover 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.
- Background: PubMed 25015420American 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.
- Background: PubMed 17640323Bajaj 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.
- Background: PubMed 29539432Fujisaka 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.
- Background: PubMed 24690956Bajaj 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.
- Background: PubMed 28790452Claesson 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.
- Background: PubMed 25982290Kelly 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Fecal microbiota transplantation delivery through colonoscopy and Fecal microbiota transplantation delivery through oral capsules in people with Hepatic Encephalopathy and Dysbiosis, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluation of safety of fecal microbiota transplantation by oral capsules in the treatment of cirrhotic patients with hepatic encephalopathy refractory to conventional therapy (time frame: 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06368895, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Sep 2026.