CirrhosisBIM-LTNCT03507140
Microbiota Study in Liver Transplanted Patients
An observational study of Cirrhosis and Hepatocellular Carcinoma, run by University Hospital, Grenoble at 1 site in France.
Trial summary
Many studies describe the relationship between microbiota alteration and the occurrence of metabolic, alcoholic or inflammatory liver diseases. Nevertheless, the modifications of microbiota during liver transplantation (LT) as well as its implication are poorly studied. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Cirrhosis, Hepatocellular Carcinoma, Liver Transplant
- What is being tested?
- Multiple sampling
- How many people
- 64 participants
- Where
- 1 siteFrance
- Study dates
- 16 Apr 2019to 27 Mar 2024
- Phase
- Observational
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients registered on the waiting list fo liver transplantation
Who may be able to join
- Recipients:
- Age ≥ 18 years old
- Absence of LT contraindications
- Patient undergoing liver transplantation
- Patient legally able to give written consent.
- Person affiliated to social security
- Donors:
- Cadaveric-donor liver transplantation
Who cannot join
- Living-related liver transplantation
- LT contraindications
- All subjects protected by articles L1121-5 and L1121-8 of French public health law (Subject under administrative or judicial control, person who are protected under the act, person hospitalized without their consent, prisoners and pregnant or breast-feeding women).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Biliary and Intestinal Microbiota Study in Liver Transplanted Patients
Many studies describe the relationship between microbiota alteration and the occurrence of metabolic, alcoholic or inflammatory liver diseases. Nevertheless, the modifications of microbiota during liver transplantation (LT) as well as its implication are poorly studied. Similarly, only the intestinal microbiota is studied in this context, and no data are available on the biliary microbiota, even if it is known that bile microbiota can interfere with hepatobiliary diseases.
This study proposes a clinical and biological in-depth follow-up with multiple sampling of liver transplanted patients to study biliary and intestinal microbiota alterations along LT, as well as bile acids metabolism in corresponding fluids.
Read more
Indeed, in recipient samples as saliva, blood, urine, and feces can be taken before LT, and surgeons can easily perform bile sampling during LT. In donors all samples can be taken during liver removal. This offers the opportunity to have a microbiotic landscape of individuals without liver disease (donor), and patients suffering from a chronic liver disease or a liver cancer before and after transplantation.
Also, in Grenoble University hospital, in case of biliary anastomotic incongruence, a biliary stent is placed during LT in 60% of recipients. This stent is removed by endoscopic retrograde cholangiopancreatography (ERCP) within 6 months after LT, offering a second opportunity to obtain bile samples in transplanted patients, after the early post-LT period. Patients who do not require a biliary stent will also be included for the study of secondary objectives, as intestinal microbiota is very poorly characterized in liver transplanted patients too. A portion of the patients without biliary stent, may also develop an anastomotic biliary stricture requiring an ERCP. If this ERCP is realized within the follow-up period of the study, the patient will also be included in the primary objective of the study.
These multiple and sequential samples will allow a complete analysis of microbiota changes in LT patients and aim to answer to 3 questions:
- What are the modifications of intestinal and biliary microbiomes during LT?
- What is the influence of bile acids' composition on intestinal and biliary microbiota?
- What are the relationships between microbiome alterations and the emergence of LT complications?
- Conditions
- Cirrhosis, Hepatocellular Carcinoma, Liver Transplant, Microbiota
- Being tested
- Multiple sampling
- Keywords
- cirrhosis, hepatocellular carcinoma, Liver transplantation, Microbiota
- Medical subject headings
- Fibrosis, Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Multiple samplingOther
Bile, saliva, feces, urine et blood samples before and after liver transplantation in recipients.
Bile, saliva, feces, urine et blood samples during liver removal in donors.
What is being measured
The primary outcome is the main question the study is designed to answer.
Comparison of the relative abundance of pathobionts and symbionts before and 6 months after liver transplantation, in the bile of recipients.
Beneficial bacterias/pathobionts ratio before and 6 months after liver transplantation in the bile of recipients.
Measured: During LT and 6 months after LT
Secondary outcomes (11)
Comparison of the relative abundance of pathobionts and beneficial bacteria at the time, and 6 months after liver transplantation, in the feces of recipients.
Intestinal beneficial bacterias/pathobionts ratio before and 6 months after liver transplantation in recipients.
Measured: Before LT (6 months maximum) and 6 months after LT
Comparison of bile microbial diversity at the time, and 6 months after liver transplantation, in LT recipients.
Proportion of the different microbial populations in recipients' bile.
Measured: During LT and 6 months after LT
Comparison of fecal microbial diversity before, and 6 months after liver transplantation, in LT recipients.
Proportion of the different microbial populations in recipients' feces.
Measured: Before LT (6 months maximum) and 6 months after LT
Study the correlation between bile microbiota of donors and recipients after LT.
Proportion of the different biliary microbial populations of donors and in their corresponding recipient.
Measured: During LT and 6 months after LT
Study the correlation between fecal microbiota of donors and recipients after LT.
Proportion of the different intestinal microbial populations of donors and their corresponding recipient.
Measured: Before LT (6 months maximum) and 6 months after LT
Study the relationships between bile microbiota changes and intestinal microbiota modifications in recipients, before and after LT.
Correlation between microbial populations' proportions in bile and in feces in donors and in recipients.
Measured: Before LT (6 months maximum) and 6 months after LT
Study the modifications of bile acid profiles in recipients between before and after LT.
Proportions of total, primary and secondary biles acids in urine, feces and bile of donors and recipients.
Measured: Before LT (6 months maximum) and 6 months after LT
Study the influence of bile acids'composition on bile microbiota along transplantation.
Correlation between the evolution of pathobionts and beneficial bacterias' proportions in bile and the different bile acids (BA) profiles (proportions of primary and secondary BAs).
Measured: Before LT (6 months maximum) and 6 months after LT
Study the influence of bile acids' composition on intestinal microbiota along transplantation.
Correlation between the evolution of pathobionts and beneficial bacterias' proportions in feces and the different bile acids profiles (proportions of primary and secondary BAs) before and after LT.
Measured: Before LT (6 months maximum) and 6 months after LT
Study the relationships between microbiota and the emergence of LT complications (post LT infections, acute liver allograft reject, etc).
Correlation between the evolution of pathobionts and beneficial bacterias' proportions in feces and the different bile acids profiles (proportions of primary and secondary BAs).
Measured: Before LT (6 months maximum) and 6 months after LT
Biobanking of blood, saliva, bile, feces and urine for further analyses such as metabolomic studies on blood, urine and feces metagenomic studies on saliva, and immunomonitoring on blood.
Measured: Before LT (6 months maximum) and 6 months after LT
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2018
- Study start16 Apr 2019
- Primary completion9 Nov 2023
- Study completion27 Mar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CirrhosisStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Grenoble
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Gael ROTH, MD, Principal investigator, GRENOBLE ALPES UNIVERSITY HOSPITAL
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03507140
- Sponsor's protocol ID
- 38RC17.332
- Acronym
- BIM-LT
- Status last verified
- Apr 2025
- First submitted
- 5 Apr 2018
- Last updated
- 20 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Biliary and Intestinal Microbiota Study in Liver Transplanted Patients
- ClinicalTrials.gov ID
- NCT03507140
- Acronym / sponsor ID
- BIM-LT / 38RC17.332
- Conditions
- Cirrhosis, Hepatocellular Carcinoma, Liver Transplant, Microbiota
- Keywords
- cirrhosis, hepatocellular carcinoma, Liver transplantation, Microbiota
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- University Hospital, GrenobleUniversity, hospital or other
- Study start
- 16 Apr 2019 (actual)
- Primary completion
- 9 Nov 2023 (actual)
- Study completion
- 27 Mar 2024 (actual)
- First posted
- 24 Apr 2018 (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.
Many studies describe the relationship between microbiota alteration and the occurrence of metabolic, alcoholic or inflammatory liver diseases. Nevertheless, the modifications of microbiota during liver transplantation (LT) as well as its implication are poorly studied. Similarly, only the intestinal microbiota is studied in this context, and no data are available on the biliary microbiota, even if it is known that bile microbiota can interfere with hepatobiliary diseases.
This study proposes a clinical and biological in-depth follow-up with multiple sampling of liver transplanted patients to study biliary and intestinal microbiota alterations along LT, as well as bile acids metabolism in corresponding fluids.
Indeed, in recipient samples as saliva, blood, urine, and feces can be taken before LT, and surgeons can easily perform bile sampling during LT. In donors all samples can be taken during liver removal. This offers the opportunity to have a microbiotic landscape of individuals without liver disease (donor), and patients suffering from a chronic liver disease or a liver cancer before and after transplantation.
Also, in Grenoble University hospital, in case of biliary anastomotic incongruence, a biliary stent is placed during LT in 60% of recipients. This stent is removed by endoscopic retrograde cholangiopancreatography (ERCP) within 6 months after LT, offering a second opportunity to obtain bile samples in transplanted patients, after the early post-LT period. Patients who do not require a biliary stent will also be included for the study of secondary objectives, as intestinal microbiota is very poorly characterized in liver transplanted patients too. A portion of the patients without biliary stent, may also develop an anastomotic biliary stricture requiring an ERCP. If this ERCP is realized within the follow-up period of the study, the patient will also be included in the primary objective of the study.
These multiple and sequential samples will allow a complete analysis of microbiota changes in LT patients and aim to answer to 3 questions:
- What are the modifications of intestinal and biliary microbiomes during LT?
- What is the influence of bile acids' composition on intestinal and biliary microbiota?
- What are the relationships between microbiome alterations and the emergence of LT complications?
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients registered on the waiting list fo liver transplantation
Key inclusion criteria (8 listed)
- Age ≥ 18 years old
- Absence of LT contraindications
- Patient undergoing liver transplantation
- Patient legally able to give written consent.
- Person affiliated to social security
Key exclusion criteria (3 listed)
- Living-related liver transplantation
- LT contraindications
- All subjects protected by articles L1121-5 and L1121-8 of French public health law (Subject under administrative or judicial control, person who are protected under the act, person hospitalized without their consent, prisoners and pregnant or breast-feeding women).
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 |
|---|---|---|
| Multiple samplingBile, saliva, feces, urine et blood samples before and after liver transplantation in recipients. Bile, saliva, feces, urine et blood samples during liver removal in donors. | Other | – |
Primary outcome
Comparison of the relative abundance of pathobionts and symbionts before and 6 months after liver transplantation, in the bile of recipients.
Time frame: During LT and 6 months after LT
Beneficial bacterias/pathobionts ratio before and 6 months after liver transplantation in the bile of recipients.
11 secondary outcomes
Comparison of the relative abundance of pathobionts and beneficial bacteria at the time, and 6 months after liver transplantation, in the feces of recipients.
Time frame: Before LT (6 months maximum) and 6 months after LT
Comparison of bile microbial diversity at the time, and 6 months after liver transplantation, in LT recipients.
Time frame: During LT and 6 months after LT
Comparison of fecal microbial diversity before, and 6 months after liver transplantation, in LT recipients.
Time frame: Before LT (6 months maximum) and 6 months after LT
Study the correlation between bile microbiota of donors and recipients after LT.
Time frame: During LT and 6 months after LT
Study the correlation between fecal microbiota of donors and recipients after LT.
Time frame: Before LT (6 months maximum) and 6 months after LT
Study the relationships between bile microbiota changes and intestinal microbiota modifications in recipients, before and after LT.
Time frame: Before LT (6 months maximum) and 6 months after LT
Study the modifications of bile acid profiles in recipients between before and after LT.
Time frame: Before LT (6 months maximum) and 6 months after LT
Study the influence of bile acids'composition on bile microbiota along transplantation.
Time frame: Before LT (6 months maximum) and 6 months after LT
Study the influence of bile acids' composition on intestinal microbiota along transplantation.
Time frame: Before LT (6 months maximum) and 6 months after LT
Study the relationships between microbiota and the emergence of LT complications (post LT infections, acute liver allograft reject, etc).
Time frame: Before LT (6 months maximum) and 6 months after LT
Biobanking of blood, saliva, bile, feces and urine for further analyses such as metabolomic studies on blood, urine and feces metagenomic studies on saliva, and immunomonitoring on blood.
Time frame: Before LT (6 months maximum) and 6 months after LT
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 20 Apr 2025.
- 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.
Gael ROTH, MD principal investigator
GRENOBLE ALPES UNIVERSITY HOSPITAL
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cirrhosis and Hepatocellular Carcinoma, run by University Hospital, Grenoble at 1 site in France.
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 8 inclusion and 3 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 20 Apr 2025. 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 France. 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.
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?
Comparison of the relative abundance of pathobionts and symbionts before and 6 months after liver transplantation, in the bile of recipients. (time frame: During LT and 6 months after LT). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 Apr 2025.