Influence of Probiotics Administration Before Liver Resection in Liver Disease (LIPROCES)

May 14, 2018 updated by: University Hospital, Rouen

Circulating Endotoxemia After Liver Resection for Hepatocellular Carcinoma in Liver Disease - Influence of Preoperative Administration of Probiotics

Surgical resection is one of the curative treatment modalities for HCC. Limits are postoperative septic and liver functional complications related to an increase in bacterial translocation and systemic endotoxemia. Bacterial translocation is a passage of bacteria and bacterial degradation products from the intestine to the portal circulation. The endotoxemia secondary to bacterial translocation, stimulates endothelial production of nitric oxide (NO). NO is also a potent inducer of membrane instability, responsible for an increase in the permeability of the vascular endothelium and intestinal mucosa, possibly contributing to a worsening of bacterial translocation.

Probiotics are live microorganisms which when administered in adequate amounts, provide a health benefit on the host ((Health and Nutritional Properties of Probiotics in Food Including Powder Milk with Live Lactic Acid Bacteria - Cordoba Argentina October 2001). Data from experimental and clinical literature show a significant effect of probiotics on the improvement of liver function and a decrease in infectious complications in patients with chronic liver disease. The proposed study would evaluate the effect preventive and therapeutic in a population of surgical patients, in whom the intestinal portal and hepatic inflammation promotes postoperative complications.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The aim of this study is to evaluate the effect of the administration of probiotics on intestinal barrier function in patients with chronic liver disease (fibrosis stage F3 or F4) operated for hepatocellular carcinoma.

After hepatectomy, kinetic of endotoxemia have been studied previously and the evolution will be summarized by the area under the plasma concentration versus time curve (AUC) of circulating endotoxin levels measured before surgery and at 5 different times analysis after hepatectomy. At 12 hours, portal hypertension and its consequences on gut permeability (impaired barrier function, bacterial translocation) are highest with peak of circulating endotoxins. The decreasing of endotoxemia curve is observed between the 2nd and 3rd day (end of liver regeneration and early liver architectural reorganization). On the 5th day, persist measurable but not deleterious to liver restructured and theoretically functional rates.

Then the main criterion to demonstrate the effectiveness of a diet enriched with probiotics is the AUC of circulating levels of endotoxins ((pg/ml) using the Limulus amebocyte lysate (LAL) assay) observed for each patient. Endotoxin levels were analysed on samples of peripheral blood. The two arms of equal size will be considered significantly different when compared to the AUC of circulating levels of endotoxin if the null hypothesis (AUC is the same for both arms) is rejected in favor of the alternative hypothesis (AUC differs between the two arms - Wilcoxon test)

In order to estimate the sample size to distinguish between the two hypotheses with sufficient power, the median AUC in arm without probiotics be used to form two groups of patients in each arm. Thus, half of the patients without probiotics have a higher median AUC arms. Then, this proportion may be compared to the proportion of patients with probiotics have an AUC greater than the median of the group without probiotics.

The secondary endpoints are:

  • Evaluation of systemic inflammation by assay of inflammatory cytokines
  • IL-2, IL-4, IL-6, IL-8, IL-10, GM-CSF, IFNa, TNFa
  • CRP
  • Leukocyte count
  • The post-operative liver function monitored in the usual manner
  • Standard Liver function tests between J1 and J5 (Bilirubin, prothrombin, ammonia)
  • Indocyanine green clearance with measuring retention rates at 15 minutes between J1 and J3
  • Monitoring of overall postoperative complications and specifically liver failure and infectious complications at 3 months.

Study Type

Interventional

Enrollment (Actual)

64

Phase

  • Not Applicable

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

  • France
    • Haute Normandie
      • Rouen, Haute Normandie, France, 76000
        • University Hospital

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 and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Agreement signed by the patient
  • Diagnosis of HCC confirmed
  • Diagnosis of liver disease (score F3 or F4) confirmed
  • Indication of surgical resection confirmed and validated by a specialist multidisciplinary assessment meeting of gastrointestinal oncology
  • Patient operable (no indication against anaesthesiological)
  • Resectable tumor lesion (surgical expertise)
  • Laboratory tests and endoscopy: No suspicion of severe portal hypertension with bleeding risk

Exclusion Criteria:

  • Patient not willing, at risk of default of compliance, or patient can not be monitored regularly
  • Antibiotic extended or terminated for less than 1 month, may limit the effects of taking probiotics.
  • Inflammatory Bowel Disease, which could skew the results expected by taking probiotics results.

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

  • Primary Purpose: OTHER
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
PLACEBO_COMPARATOR: Placebo of Probiotics

Placebo: Composition: Each capsule contains 560 mg:

  • 459 mg of corn starch
  • 6 mg of magnesium stearate

Dosage: 2 capsules / day, in the morning at sunrise, one at bedtime.

Methods of administration: Oral.

Duration of treatment: 14 days
Dietary supplement: Placebo
ACTIVE_COMPARATOR: Probiotics- Lactibiane Tolerance

Active substance mixture of lactic 10% Bifidobacterium lactis LA 303, 10% Lactobacillus acidophilus LA 201, LA 40% Lactobacillus plantarum 301, 20% Lactobacillus salivarius LA 302, LA 20% Bifidobacterium lactis 304 Dosage: 10 X 10^9 probiotic / capsule

Composition: One capsule of 560 mg contains Lactibiane tolerance:

  • 345 mg of corn starch
  • 114 mg premix lactic
  • 6 mg of magnesium stearate Excipients: magnesium stearate

Method of administration: Oral

Dosage: 2 capsules per day for 14 days in two doses: one capsule at sunrise, one capsule at bedtime;
Dietary supplement: Probiotic
Lactibiane TOLERANCE vs Placebo
Other Names:
  • Lactibiane TOLERANCE (PILeJe) 5 probiotics association

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Area under the plasma concentration versus time curve (AUC) of endotoxins circulating levels
Time Frame: -12, 3, 12,24, 72, 120 hours at time of surgery
-12, 3, 12,24, 72, 120 hours at time of surgery

Collaborators and Investigators

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

Sponsor

University Hospital, Rouen

Investigators

  • Study Director: Lilian Schwarz, MD, DRCI Rouen
  • Principal Investigator: Emmanuel Huet, MD, DRCI Rouen

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

April 1, 2013

Primary Completion (ACTUAL)

April 12, 2018

Study Completion (ACTUAL)

April 12, 2018

Study Registration Dates

First Submitted

July 3, 2013

First Submitted That Met QC Criteria

December 19, 2013

First Posted (ESTIMATE)

December 27, 2013

Study Record Updates

Last Update Posted (ACTUAL)

May 15, 2018

Last Update Submitted That Met QC Criteria

May 14, 2018

Last Verified

May 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2012/130/HP

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.

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