Influence of Probiotics on Infections in Cirrhosis (PIC)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Austrian Science Fund (FWF)
Information provided by (Responsible Party):
Medical University of Graz
ClinicalTrials.gov Identifier:
NCT01607528
First received: April 13, 2012
Last updated: April 4, 2014
Last verified: April 2014
  Purpose

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 Intervention
Liver Cirrhosis
Dietary Supplement: Winclove-849
Dietary Supplement: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Probiotic Modulation of Gut Microflora in Cirrhosis: Influence on Immune Function and Infections

Resource links provided by NLM:


Further study details as provided by Medical University of Graz:

Primary Outcome Measures:
  • Change in neutrophil phagocytic capacity [ Time Frame: Change from baseline to 6 months ] [ Designated as safety issue: No ]
    Percentage of neutrophil granulocytes showing phagocytosis of FITC-labelled E.coli bacteria


Secondary Outcome Measures:
  • Number of clinically significant infections [ Time Frame: during 12 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Endotoxin in serum (EU/ml)

  • neutrophil oxidative burst [ Time Frame: 0, 6, 12 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    percentage of neutrophil granulocytes showing TLR2, TLR4 or TLR9 expression and mean fluorescence activity

  • albumin oxidation [ Time Frame: 0, 6, 12 months ] [ Designated as safety issue: No ]
    oxidative status of albumin in the plasma (percentage of HMA, HNA1 and HNA2)

  • inflammatory response [ Time Frame: 0, 6, 12 months ] [ Designated as safety issue: Yes ]
    elevation of one or more inflammatory markers: C reactive protein (mg/ml), lipopolysaccharide binding protein (ng/ml), soluble CD14 (ng/ml)

  • bacterial flora [ Time Frame: 0, 6, 12 months ] [ Designated as safety issue: No ]
    isolation of bacterial DNA and sequencing the gut microbiome from stool and duodenal aspirate

  • quality of life [ Time Frame: 0, 6, 12 months ] [ Designated as safety issue: No ]
    SF-36 questionaire

  • nutritional status [ Time Frame: 0,6, 12 months ] [ Designated as safety issue: No ]
    subjective global assessment


Estimated Enrollment: 92
Study Start Date: July 2012
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01607528

Locations
Austria
Department of Internal Medicine, Medical University of Geraz
Graz, Austria, 8036
Sponsors and Collaborators
Medical University of Graz
Austrian Science Fund (FWF)
Investigators
Principal Investigator: Vanessa Stadlbauer-Köllner, MD Medical University of Graz
  More Information

No publications provided

Responsible Party: Medical University of Graz
ClinicalTrials.gov Identifier: NCT01607528     History of Changes
Other Study ID Numbers: PIC-2010
Study First Received: April 13, 2012
Last Updated: April 4, 2014
Health Authority: Austria: Ethikkommission

Additional relevant MeSH terms:
Liver Cirrhosis
Liver Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on September 22, 2014