Influence of Probiotics on Infections in Cirrhosis

Liver Cirrhosis Clinical Trial

— PIC  

Official title:

Probiotic Modulation of Gut Microflora in Cirrhosis: Influence on Immune Function and Infections

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01607528
• Other study ID #: PIC-2010
• Status: Completed
• Phase: N/A
• First received: April 13, 2012
• Last updated: May 4, 2016
• Start date: July 2012
• Est. completion date: September 2014

Study information

• Verified date: May 2016
• Source: Medical University of Graz
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Ethikkommission
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 92
• Est. completion date: September 2014
• Est. primary completion date: March 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria: • Patients aged between 18-80 years

• Clinical and radiological evidence of cirrhosis, and/or biopsy proven liver cirrhosis of any cause

• Informed consent

Exclusion Criteria:

• Child-Pugh score > 11

• Abstinence from alcohol for < 2 weeks at the time of screening for inclusion

• Clinical evidence of active infection

• Antibiotic treatment within 7 days prior to enrolment

• Gastrointestinal haemorrhage within previous 2 weeks

• Use of immunomodulating agents within previous month (steroids etc.)

• Use of proton pump inhibitors for preceding two weeks

• Concomitant use of supplements (pre-, pro-, or synbiotics) likely to influence the study

• Renal failure (such as hepatorenal syndrome), creatinine >1.7 mg/dL

• Hepatic encephalopathy II to IV

• Pancreatitis

• Other organ failure

• Hepatic or extra-hepatic malignancy

• Pregnancy

• Presumed non-compliance to the study medication

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Liver Cirrhosis

Intervention

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
A similar looking and tasting powder with no active substances

Locations

Country	Name	City	State
Austria	Department of Internal Medicine, Medical University of Geraz	Graz

Sponsors (2)

Lead Sponsor	Collaborator
Medical University of Graz	Austrian Science Fund (FWF)

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in neutrophil phagocytic capacity	Percentage of neutrophil granulocytes showing phagocytosis of FITC (fluorescein isothiocyanate) -labelled E.coli bacteria	Change from baseline to 6 months	No
Secondary	Number of clinically significant infections	Occurence of infections that require specific treatment and/or hospitalisation during the study period of 12 months	during 12 months	No
Secondary	endotoxin levels	Endotoxin in serum (EU/ml)	0, 6, 12 months	No
Secondary	neutrophil oxidative burst	percentage of neutrophil granulocytes showing oxidative burst with and without stimulation and mean fluorescence activity	0, 6, 12 months	No
Secondary	neutrophil toll like receptor expression	percentage of neutrophil granulocytes showing TLR (Toll-like receptor) 2, TLR4 or TLR9 expression and mean fluorescence activity	0, 6, 12 months	No
Secondary	albumin oxidation	oxidative status of albumin in the plasma (percentage of (human mercaptalbumin) HMA, (human non-mercaptalbumin) HNA1 and HNA2)	0, 6, 12 months	No
Secondary	inflammatory response	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)	0, 6, 12 months	Yes
Secondary	bacterial flora	isolation of bacterial DNA and sequencing the gut microbiome from stool and duodenal aspirate	0, 6, 12 months	No
Secondary	quality of life	(short form) SF-36 questionaire	0, 6, 12 months	No
Secondary	nutritional status	subjective global assessment	0,6, 12 months	No
Secondary	changes in gut permeability over time	elevated lactulose mannitol ratio, elevated zonulin	0, 6, 12 months	No