Liver FibrosisLIPROCESNCT02021253
Influence of Probiotics Administration Before Liver Resection in Liver Disease
A study testing Probiotic in people with Liver Fibrosis and Liver Cirrhosis, run by University Hospital, Rouen at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Fibrosis, Liver Cirrhosis, Permeability; Increased
- What is being tested?
- Probiotic
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 64 participants
- Where
- 1 siteFrance
- Study dates
- Apr 2013to 12 Apr 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Being tested
- Probiotic, Placebo
- Keywords
- Endotoxemia, Probiotic, Leaky gut, Gut permeability, Liver cirrhosis, Liver fibrosis, Hepatocellular carcinoma
- Medical subject headings
- Liver Cirrhosis, Carcinoma, Hepatocellular, Endotoxemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ProbioticDietary supplement
Also called Lactibiane TOLERANCE (PILeJe) 5 probiotics association
Lactibiane TOLERANCE vs Placebo
PlaceboDietary supplement
| Study group | Role | What they receive |
|---|---|---|
| Placebo of Probiotics | Placebo comparator | 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 Receives: Dietary Supplement: Placebo |
| Probiotics- Lactibiane Tolerance | Active comparator | 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; Receives: Dietary Supplement: Probiotic |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under the plasma concentration versus time curve (AUC) of endotoxins circulating levels
Measured: -12, 3, 12,24, 72, 120 hours at time of surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Dec 2013 (estimated)
- Study startApr 2013
- Primary completion12 Apr 2018
- Study completion12 Apr 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Liver FibrosisStudies of the same condition, open and under way.
- More trials run by University Hospital, RouenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Rouen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lilian Schwarz, MD, Study director, DRCI RouenEmmanuel Huet, MD, Principal investigator, DRCI Rouen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02021253
- Sponsor's protocol ID
- 2012/130/HP
- Acronym
- LIPROCES
- Status last verified
- May 2018
- First submitted
- 3 Jul 2013
- Last updated
- 15 May 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
Roussel E, Brasse-Lagnel C, Tuech JJ, Montialoux H, Papet E, Tortajada P, Bekri S, Schwarz L. Influence of Probiotics Administration Before Liver Resection in Patients with Liver Disease: A Randomized Controlled Trial. World J Surg. 2022 Mar;46(3):656-665. doi: 10.1007/s00268-021-06388-7. Epub 2021 Nov 26.
PubMed 34837121
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Circulating Endotoxemia After Liver Resection for Hepatocellular Carcinoma in Liver Disease - Influence of Preoperative Administration of Probiotics
- ClinicalTrials.gov ID
- NCT02021253
- Acronym / sponsor ID
- LIPROCES / 2012/130/HP
- Keywords
- Endotoxemia, Probiotic, Leaky gut, Gut permeability, Liver cirrhosis, Liver fibrosis, Hepatocellular carcinoma
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- University Hospital, RouenUniversity, hospital or other
- Study start
- Apr 2013
- Primary completion
- 12 Apr 2018 (actual)
- Study completion
- 12 Apr 2018 (actual)
- First posted
- 27 Dec 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo of Probiotics | Placebo comparator | Dietary Supplement: PlaceboPlacebo: 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 |
| Probiotics- Lactibiane Tolerance | Active comparator | Dietary Supplement: ProbioticActive 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; |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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)
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ProbioticAlso: Lactibiane TOLERANCE (PILeJe) 5 probiotics associationLactibiane TOLERANCE vs Placebo | Dietary supplement | Probiotics- Lactibiane Tolerance |
| Placebo | Dietary supplement | Placebo of Probiotics |
Primary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2018.
- Derived from this study: PubMed 34837121Roussel E, Brasse-Lagnel C, Tuech JJ, Montialoux H, Papet E, Tortajada P, Bekri S, Schwarz L. Influence of Probiotics Administration Before Liver Resection in Patients with Liver Disease: A Randomized Controlled Trial. World J Surg. 2022 Mar;46(3):656-665. doi: 10.1007/s00268-021-06388-7. Epub 2021 Nov 26.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lilian Schwarz, MD study director
DRCI Rouen
Emmanuel Huet, MD principal investigator
DRCI Rouen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Probiotic in people with Liver Fibrosis and Liver Cirrhosis, run by University Hospital, Rouen at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02021253, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2018.