Influence of Probiotics on Infections in Cirrhosis (PIC)
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|ClinicalTrials.gov Identifier: NCT01607528|
Recruitment Status : Completed
First Posted : May 30, 2012
Last Update Posted : May 5, 2016
Liver cirrhosis is the 10th most common cause of death in the western world. Infection is the most common precipitant of deterioration of liver function in cirrhosis. Endotoxin, derived from gram-negative organisms in the gut, can enter the circulation due to increased gut permeability and contributes to neutrophil dysfunction, infection risk and mortality in alcoholic cirrhotics. As probiotics decrease gram-negative organisms in the gut and/or decrease gut permeability, the investigators hypothesize that probiotic treatment would restore neutrophil function and prevent infection in alcoholic cirrhosis.
The investigators hypothesize that administration of a probiotic mixture in patients with liver cirrhosis will improve innate immune function through alteration of the gut bacterial flora and gut barrier integrity.
The aim of this randomised, double-blinded placebo-controlled study is to assess whether food supplementation with probiotic mixture improves neutrophil phagocytic capacity in patients with cirrhosis and decreases the incidence of significant infections.
92 patients with alcoholic cirrhosis will be included according to a sample size calculation from preliminary data. Patients will be randomized in two groups: Group 1 receives a probiotic mixture Group 2 receives a similar looking and tasting placebo without bacteria. The recruited patients will be treated for 6 months. Besides routine clinical and laboratory assessments, neutrophil function, toll-like receptor expression, endotoxin levels, bacterial DNA, cytokine levels, albumin oxidation, gut permeability and analysis of gut microflora will be performed. Furthermore nutritional status and quality of life will be assessed.
Primary endpoints will be neutrophil phagocytosis. Secondary endpoints will be significant infection, neutrophil oxidative burst, neutrophil toll-like receptor expression, endotoxin levels, bacterial DNA; cytokine levels, albumin oxidation, gut barrier function and bacterial flora, nutritional status and quality of life.
If our hypothesis holds true, probiotics will provide an easily applicable and cost effective method to improve immune function and to prevent infection in liver cirrhosis. It is possible that this can improve survival of patients with liver cirrhosis.
|Condition or disease||Intervention/treatment||Phase|
|Liver Cirrhosis||Dietary Supplement: Winclove-849 Dietary Supplement: Placebo||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||92 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Probiotic Modulation of Gut Microflora in Cirrhosis: Influence on Immune Function and Infections|
|Study Start Date :||July 2012|
|Actual Primary Completion Date :||March 2014|
|Actual Study Completion Date :||September 2014|
Active Comparator: Probiotic
6 g of Winclove-849 containing Bifidobacterium bifidum W23, Bifidobacterium lactis W52, Lactobacillus acidophilus W37, Lactobacillus brevis W63, Lactobacillus casei W56, Lactobacillus salivarius W24, Lactococcus lactis W19, Lactococcus lactis W58 at a concentration of 2.5 x 10E9 cfu/g per day
Dietary Supplement: Winclove-849
6 g of Winclove-849 containing Bifidobacterium bifidum W23, Bifidobacterium lactis W52, Lactobacillus acidophilus W37, Lactobacillus brevis W63, Lactobacillus casei W56, Lactobacillus salivarius W24, Lactococcus lactis W19, Lactococcus lactis W58 at a concentration of 2.5 x 109 cfu/g
Placebo Comparator: Placebo
A similar looking and tasting powder
Dietary Supplement: Placebo
A similar looking and tasting powder with no active substances
- Change in neutrophil phagocytic capacity [ Time Frame: Change from baseline to 6 months ]Percentage of neutrophil granulocytes showing phagocytosis of FITC (fluorescein isothiocyanate) -labelled E.coli bacteria
- Number of clinically significant infections [ Time Frame: during 12 months ]Occurence of infections that require specific treatment and/or hospitalisation during the study period of 12 months
- endotoxin levels [ Time Frame: 0, 6, 12 months ]Endotoxin in serum (EU/ml)
- neutrophil oxidative burst [ Time Frame: 0, 6, 12 months ]percentage of neutrophil granulocytes showing oxidative burst with and without stimulation and mean fluorescence activity
- neutrophil toll like receptor expression [ Time Frame: 0, 6, 12 months ]percentage of neutrophil granulocytes showing TLR (Toll-like receptor) 2, TLR4 or TLR9 expression and mean fluorescence activity
- albumin oxidation [ Time Frame: 0, 6, 12 months ]oxidative status of albumin in the plasma (percentage of (human mercaptalbumin) HMA, (human non-mercaptalbumin) HNA1 and HNA2)
- inflammatory response [ Time Frame: 0, 6, 12 months ]elevation of one or more inflammatory markers: C reactive protein (mg/ml), lipopolysaccharide binding protein (ng/ml), soluble CD (cluster of differentiation) 14 (ng/ml)
- bacterial flora [ Time Frame: 0, 6, 12 months ]isolation of bacterial DNA and sequencing the gut microbiome from stool and duodenal aspirate
- quality of life [ Time Frame: 0, 6, 12 months ](short form) SF-36 questionaire
- nutritional status [ Time Frame: 0,6, 12 months ]subjective global assessment
- changes in gut permeability over time [ Time Frame: 0, 6, 12 months ]elevated lactulose mannitol ratio, elevated zonulin
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): NCT01607528
|Department of Internal Medicine, Medical University of Geraz|
|Graz, Austria, 8036|
|Principal Investigator:||Vanessa Stadlbauer-Köllner, MD||Medical University of Graz|