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
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|
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
- 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 (Clinical Trial)|
|Actual Enrollment :||64 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|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|
Placebo Comparator: Placebo of Probiotics
Placebo: Composition: Each capsule contains 560 mg:
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:
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
- 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 ]
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
|Rouen, Haute Normandie, France, 76000|
|Study Director:||Lilian Schwarz, MD||DRCI Rouen|
|Principal Investigator:||Emmanuel Huet, MD||DRCI Rouen|