Clinical trial NCT01607528: Influence of Probiotics on Infections in Cirrhosis
Official title: Probiotic Modulation of Gut Microflora in Cirrhosis: Influence on Immune Function and Infections
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Liver Cirrhosis
Lead sponsor: Medical University of Graz
Sponsor class: OTHER
Collaborators: name: Austrian Science Fund (FWF)
First posted: 2012-05-30
Enrollment: 92
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Change in neutrophil phagocytic capacity
timeFrame: Change from baseline to 6 months
Secondary outcomes:
measure: Number of clinically significant infections
timeFrame: during 12 months
measure: endotoxin levels
timeFrame: 0, 6, 12 months
measure: neutrophil oxidative burst
timeFrame: 0, 6, 12 months
measure: neutrophil toll like receptor expression
timeFrame: 0, 6, 12 months
measure: albumin oxidation
timeFrame: 0, 6, 12 months
measure: inflammatory response
timeFrame: 0, 6, 12 months
measure: bacterial flora
timeFrame: 0, 6, 12 months
measure: quality of life
timeFrame: 0, 6, 12 months
measure: nutritional status
timeFrame: 0,6, 12 months
measure: changes in gut permeability over time
timeFrame: 0, 6, 12 months
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Department of Internal Medicine, Medical University of Geraz
Study officials:
affiliation: Medical University of Graz
name: Vanessa Stadlbauer-Köllner, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.