Influence of Probiotics on Infections in Cirrhosis

NCT ID: NCT01607528

Last Updated: 2016-05-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 92 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-07-31
• Study Completion Date: 2014-09-30

Brief 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.

Conditions

Liver Cirrhosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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

Group Type: ACTIVE_COMPARATOR

Winclove-849

Intervention Type: DIETARY_SUPPLEMENT

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DIETARY_SUPPLEMENT

A similar looking and tasting powder with no active substances

Interventions

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

Intervention Type: DIETARY_SUPPLEMENT

Placebo

A similar looking and tasting powder with no active substances

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Austrian Science Fund (FWF)

OTHER

Sponsor Role: collaborator

Medical University of Graz

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Vanessa Stadlbauer-Köllner, MD

Role: PRINCIPAL_INVESTIGATOR

Medical University of Graz

Locations

Department of Internal Medicine, Medical University of Geraz

Graz, , Austria

Countries

Austria

References

Egger M, Horvath A, Pruller F, Fickert P, Finkelman M, Kriegl L, Gronbaek H, Moller HJ, Prattes J, Krause R, Hoenigl M, Stadlbauer V. Fungal translocation measured by serum 1,3-ss-D-glucan correlates with severity and outcome of liver cirrhosis-A pilot study. Liver Int. 2023 Sep;43(9):1975-1983. doi: 10.1111/liv.15648. Epub 2023 Jun 19.

Reference Type: DERIVED

PMID: 37334864 (View on PubMed)

Stadlbauer V, Komarova I, Klymiuk I, Durdevic M, Reisinger A, Blesl A, Rainer F, Horvath A. Disease severity and proton pump inhibitor use impact strongest on faecal microbiome composition in liver cirrhosis. Liver Int. 2020 Apr;40(4):866-877. doi: 10.1111/liv.14382. Epub 2020 Jan 24.

Reference Type: DERIVED

PMID: 31943691 (View on PubMed)

Other Identifiers

PIC-2010

Identifier Type: -

Identifier Source: org_study_id