Human Microbiota and Liver Transplant

August 3, 2021 updated by: Cristina Dopazo Taboada, Hospital Vall d'Hebron

Prospective Study To Characterize The Human Microbiota In Liver Transplantation And Its Impact On Early Outcome

The microbiota represents the collections of microbial communities that colonize a host. In health, the microbiota protects against pathogens and maturation of the immune system. In return, the immune system determines the composition of the microbiota. Altered microbial composition (dysbiosis) has been correlated with a number of diseases in humans. The real role of the microbiota in transplant recipients is still unknown even though we suspect that it may be affected directly or indirectly by immunosuppressive drugs and antimicrobial prophylaxis taken by transplant patients, as well as by inflammatory process secondary to ischemia/reperfusion injury.

A number of studies have investigated the impact of liver transplantation on the intestinal microbiota. In a recent analysis of stool flora (Microb Ecol 2013; 65: 781-791) in 12 liver transplant recipients, changes in the microbiota were correlated to post-transplant infections. The authors suggested that the shift to pathogenic strains of bacteria due to the use of prophylactic antibiotics may be contributing to post-transplant complications. In a larger study, Wu et al (Hepatobiliary Pancreat Dis Int 2012; 11: 40-50) demonstrated marked changes in the gut microbiota post-transplantation with an increase in Enterobacteriaceae and Enterococcus, and reduction in Eubacteria, Bifidobacterium and Lactobacillus species. These changes, however, resolved over time such that by 6 months, at times when bacterial prophylaxis ends and immunosuppression is reduced.

A better characterization of the impact of post-transplant therapy on the human microbiota has the potential to improve our understanding of the infection process and translate into development of new therapeutic strategies.

The main goal of this study is to characterize intestinal microbiota and confirm the same bacterial DNA in peripheral blood and portal lymph nodes in patients affected with end-stage chronic liver disease, and to analyze its evolution from the moment of inclusion in waiting list throughout the first year after liver transplantation. For each patient, a healthy CONTROL with a similar age (± 10 years) will be selected from the same family setting, in whom just one sample will be obtained during the enrollment phase.

The second goal is to analyze the potential associations between microbiota flora and transplant outcomes during the same period.

Study Overview

Status

Completed

Conditions

Study Type

Observational

Enrollment (Anticipated)

40

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Barcelona, Spain, 08035
        • Institut de Recerca Hospital Vall d´Hebron

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 68 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Adult liver transplant patients in Hospital Vall d´Hebron (Barcelona, Spain)

Description

Inclusion Criteria:

  • First liver transplant
  • Patients aged 18-70 years
  • Able to consent and agree in participate in the current study for one year

Exclusion Criteria:

  • Multiorgan transplantation and/or liver transplant from cardiac arrest donor and/or with ABO incompatibility.
  • Uncontrolled concomitant infections (including HIV seropositivity) and/or diarrhoea, vomiting or active gastric ulcer.
  • Fulminant hepatic insufficiency as first indication for liver transplant
  • Hemodynamic instability prior to liver transplant.
  • Recipient presenting present or previous neoplasia, except for non-metastatic basal of squamous cutaneous carcinoma or localized hepatocarcinoma with diameter <5cm or <3known lesions with diameter <3cm.
  • Significant comorbidity
  • Breastfeeding or female patients at fertile age without negative pregnancy test and accepting the use of reliable fertility control method
  • Any pretransplant antibiotherapy (oral or endovenous) or enrolled in any clinical assay

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
CASE-CONTROL
CASE: Liver transplant recipients (n=20) CONTROL: A healthy person with a similar age (±10 years) to the control selected from the same family setting (n=20)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Analyses of changes in microbiota composition before and post-transplant
Time Frame: Before transplant, 1st, 3rd, 7th, 14th and 28th post-transplant and 3rd, 6th, 9th and 12th months post-transplant

Stool samples will be obtained from the liver transplant recipient following the time frame described above.

A healthy CONTROL with a similar age (± 10 years) will be selected from the same family setting, in whom just one sample will be obtained during the enrollment phase
Before transplant, 1st, 3rd, 7th, 14th and 28th post-transplant and 3rd, 6th, 9th and 12th months post-transplant

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of biopsy proven acute cellular rejection
Time Frame: Evaluation at 3rd, 6th, 9th and 12th months post-trasplant
If liver dysfunction is observed, percutaneous liver biopsy will be performed and histological severity will be searching following the Banff criteria
Evaluation at 3rd, 6th, 9th and 12th months post-trasplant
Incidence of post-transplant infection requiring antibiotherapy (oral or endovenous)
Time Frame: Evaluation at 3rd, 6th, 9th and 12th months post-trasplant
Evaluation at 3rd, 6th, 9th and 12th months post-trasplant
Incidence of Diabetes Mellitus de novo post-transplant
Time Frame: 12 months post-trasplant
12 months post-trasplant
Incidence of Obesity (BMI≥30 kg/m2) post-transplant
Time Frame: 12 months post-transplant
12 months post-transplant
Incidence of renal dysfunction (creatinine ≥ 1.5mg/dL and/or MDRD formula Glomerular Filtrate Rate < 60 mL/min/1.73m2)
Time Frame: Evaluation at 3rd, 6th, 9th and 12th months post-trasplant
Evaluation at 3rd, 6th, 9th and 12th months post-trasplant
Patient and graft survival rates
Time Frame: Evaluation at 3rd, 6th, 9th and 12th months post-trasplant
Evaluation at 3rd, 6th, 9th and 12th months post-trasplant

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospital Vall d'Hebron

Investigators

  • Principal Investigator: ITXARONE BILBAO, PhD/MD, Department of HPB Surgery and Transplants, Hospital Vall d´Hebron (Barcelona, Spain)
  • Study Chair: Chaysavanh Manichanh, PhD/MD, Physiology and Pathophysiology of the Digestive Tract, Institut de Recerca Vall d´Hebron, Barcelona (Spain)
  • Study Chair: CRISTINA DOPAZO, PhD/MD, Department of HPB Surgery and Transplants, Hospital Vall d´Hebron (Barcelona, Spain)
  • Study Chair: Francisco Guarner, PhD/MD, Department of Gastroenterology Disease, Hospital Vall d´Hebron (Barcelona, Spain)
  • Study Chair: Mireia Caralt, PhD/MD, Department of HBP Surgery and Transplants, Hospital Vall d´Hebron (Barcelona, Spain)
  • Study Chair: Lluis Castells, PhD/MD, Department of Internal Medicine, Liver Unit, Hospital Vall d´Hebron (Barcelona, Spain)
  • Study Chair: Jose Luis Lazaro, MD, Department of HBP Surgery and Transplants, Hospital Vall d´Hebron (Barcelona, Spain)
  • Study Chair: Fernando Azpiroz, PhD/MD, Department of Gastroenterology Disease, Hospital Vall d´Hebron (Barcelona, Spain)
  • Study Chair: Ramón Charco, PhD/MD, Department of HBP Surgery and Transplants, Hospital Vall d´Hebron (Barcelona, Spain)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2016

Primary Completion (Actual)

August 1, 2021

Study Completion (Actual)

August 1, 2021

Study Registration Dates

First Submitted

August 18, 2014

First Submitted That Met QC Criteria

August 21, 2014

First Posted (Estimate)

August 22, 2014

Study Record Updates

Last Update Posted (Actual)

August 4, 2021

Last Update Submitted That Met QC Criteria

August 3, 2021

Last Verified

August 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Microta.LT.14

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Infection

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Singapore

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe