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

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ClinicalTrials.gov Identifier: NCT02021253
Recruitment Status : Completed
First Posted : December 27, 2013
Last Update Posted : May 15, 2018
Sponsor:
Information provided by (Responsible Party):
University Hospital, Rouen

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Liver Fibrosis Liver Cirrhosis Permeability; Increased Hepatocellular Carcinoma Dietary Supplement: Probiotic Dietary Supplement: Placebo Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 64 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Other
Official Title: Circulating Endotoxemia After Liver Resection for Hepatocellular Carcinoma in Liver Disease - Influence of Preoperative Administration of Probiotics
Study Start Date : April 2013
Actual Primary Completion Date : April 12, 2018
Actual Study Completion Date : April 12, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Liver Diseases

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 Name: Lactibiane TOLERANCE (PILeJe) 5 probiotics association




Primary Outcome Measures :
  1. 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 ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02021253


Locations
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France
University Hospital
Rouen, Haute Normandie, France, 76000
Sponsors and Collaborators
University Hospital, Rouen
Investigators
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Study Director: Lilian Schwarz, MD DRCI Rouen
Principal Investigator: Emmanuel Huet, MD DRCI Rouen
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Responsible Party: University Hospital, Rouen
ClinicalTrials.gov Identifier: NCT02021253    
Other Study ID Numbers: 2012/130/HP
First Posted: December 27, 2013    Key Record Dates
Last Update Posted: May 15, 2018
Last Verified: May 2018
Keywords provided by University Hospital, Rouen:
Endotoxemia
Probiotic
Leaky gut
Gut permeability
Liver cirrhosis
Liver fibrosis
Hepatocellular carcinoma
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Hepatocellular
Liver Cirrhosis
Liver Diseases
Fibrosis
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Pathologic Processes
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases