Enteric Microbiome and Liver Transplantation

NCT03666312 | Unknown

• 1 other identifier: ENT-LIVTRA
• Study Type: observational
• Target: 275
• Locations: 1 country
• Sites: 3

Brief Summary

Liver transplantation (LT) has changed the life expectancy of end-stage liver disease (ELD) patients. However, important issues may hamper the early post-LT period (e.g. graft dysfunctions, infectious complications). Risk stratification in ELD patients is based on clinical scores which are often not predictive for the LT outcomes. More robust scores are therefore needed. It is known that microbial flora may play an important role in predisposing to several pathological conditions. This is particularly true for the liver, which is constantly exposed to high load of gut microbial antigens and metabolites. The effects of these factors have not been studied on the transplanted liver yet. The investigators will study the faecal microbiome of 275 LT patients, and, in combination with a large panel of clinical, lab and functional parameters, will correlate it to different clinical outcomes. In particular, the following possible LT outcomes will be addressed:

1. 1.Early allograft dysfunction (30-40% estimated incidence)
2. 2.Treated acute cellular rejection (10-15%). Evaluated through lab parameters of liver damage and, when possible, confirmed by histopathological evaluation of liver biopsies
3. 3.Infectious complications (10-15% divided in microbiologically confirmed and clinically suspected)
4. 4.Length of stay in the hospital after LT
5. 5.Mortality at 30, 90 and 365 days (7-8% at 1 year)
6. 6.Biliary complications (10-15%)

Conditions

Orthotopic Liver Transplantation

Keywords

Enteric microbiome; Liver transplantation

Outcome Measures

Primary Outcomes (1)

• Early allograft dysfunction

  30-40% estimated incidence

  First seven days following LT

Secondary Outcomes (5)

• Treated acute cellular rejection

  Until one year following LT

• Infectious complications

  Until one year following LT

• Length of stay (LOS) in the hospital after LT

  Until 3 months following LT

• Mortality

  At 30, 90 and 365 days post-LT

• Biliary complications

  Until one year following LT

Study Arms (2)

Cohort A

The study will include patients from the two main Italian liver transplantation centers (Ospedale Le Molinette, Torino and Azienda Ospedaliera Pisana, Pisa), allowing to enroll 220 patients in the first 18 months of the proposed study. More in details, all \>18-years-old patients listed for and undergoing liver transplantation will be included in the study after signing an informed consent. Each patient will then be prospectively followed one year.

Cohort B

A second cohort of 55 patients will then be enrolled in the following 6 months as internal validation sample, and will be analogously monitored until the end of the 3-years-long study.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

The study will include patients from the two main Italian liver transplantation centers (Ospedale Le Molinette, Torino and Azienda Ospedaliera Pisana, Pisa), allowing to enroll 220 patients in the first 18 months of the proposed study. More in details, all \>18-years-old patients listed for and undergoing liver transplantation will be included in the study after signing an informed consent. Each patient will then be prospectively followed one year. A second cohort of 55 patients will then be enrolled in the following 6 months as internal validation sample, and will be analogously monitored until the end of the 3-years-long study.

You may qualify if:

• \>=18 years old
• Enlisted for and undergoing OLT during the period of the study
• Signing of the informed consent

You may not qualify if:

• \- \< 18 years-old undergoing OLT

Sponsors & Collaborators

• Nicasio Mancini: lead
• A.O.U. Città della Salute e della Scienza: collaborator
• Azienda Ospedaliero, Universitaria Pisana: collaborator

Study Sites (3)

IRCCS San Raffaele

Milan, 20132, Italy

ACTIVE NOT RECRUITING

Azienda Ospedaliero, Universitaria Pisana

Pisa, Italy

RECRUITING

Azienda Ospedaliera Città della Salute e della Scienza di Torino

Torino, Italy

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Plasma and stool samples

Study Officials

• Nicasio Mancini

  IRCCS San Raffaele

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Renée Pasciuta, M.Sc.

CONTACT

+390226434704; pasciuta.renee@hsr.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medical Microbiology and Virology

Study Record Dates

• First Submitted: September 6, 2018
• First Posted: September 11, 2018
• Study Start: September 1, 2018
• Primary Completion: August 30, 2021
• Study Completion: August 30, 2021
• Last Updated: March 1, 2019

Record last verified: 2019-02

Locations

IT (3)