Influence of Probiotics on Infections in Cirrhosis

NCT01607528 | Completed DMC

• 1 other identifier: PIC-2010
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (10)

• Number of clinically significant infections

  during 12 months

• endotoxin levels

  0, 6, 12 months

• neutrophil oxidative burst

  0, 6, 12 months

• neutrophil toll like receptor expression

  0, 6, 12 months

• albumin oxidation

  0, 6, 12 months

Study Arms (2)

Probiotic

ACTIVE COMPARATOR

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

Placebo

PLACEBO COMPARATOR

A similar looking and tasting powder

Dietary Supplement: Placebo

Interventions

Winclove-849 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

Probiotic

Placebo DIETARY_SUPPLEMENT

A similar looking and tasting powder with no active substances

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Child-Pugh score \> 11
• 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

Sponsors & Collaborators

• Medical University of Graz: lead
• Austrian Science Fund (FWF): collaborator

Study Sites (1)

Department of Internal Medicine, Medical University of Geraz

Graz, 8036, Austria

Location

Related Publications (2)

• 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.

  PMID: 37334864 DERIVED

• 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.

  PMID: 31943691 DERIVED

MeSH Terms

Conditions

Liver Cirrhosis

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Vanessa Stadlbauer-Köllner, MD

  Medical University of Graz

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 13, 2012
• First Posted: May 30, 2012
• Study Start: July 1, 2012
• Primary Completion: March 1, 2014
• Study Completion: September 1, 2014
• Last Updated: May 5, 2016

Record last verified: 2016-05

Locations

AU (1)