Modulation of Gut Microbiota in Early Sepsis: A Pilot Study

NCT ID: NCT02469571

Last Updated: 2018-03-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-09-01
• Study Completion Date: 2018-03-01

Brief Summary

Background Sepsis is a common disease leading to high morbidity and mortality. Gut microbiota and/or gut permeability may play a crucial role in the development of organ dysfunction.

Hypothesis The ingestion of a multispecies probiotic in early sepsis is able to modulate gut microbiota and/or gut permeability.

Detailed Description

Sepsis is a systemic deleterious host response to infection causing major healthcare problems. Sepsis affects millions of people around the world each year, with a lethality of 25%-50%. The incidence is increasing partly because of a raise in average age and occurrence of predisposing diseases in the population, and partly because of shifts in causative pathogens. Effectiveness of therapy administered in the initial hours of severe sepsis critically influences the clinical outcome of the patient.

Lacking reliable biomarkers for early stages, the diagnosis of (severe) sepsis relies on a combination of surrogate parameters indicating end organ dysfunction.

Recently, gut wall integrity has been identified as a key feature in protecting the body against potentially harmful compounds such as bacteria, toxins and antigens. The gut barrier consists of the mucus barrier, antimicrobial peptides, secretory IgA, the epithelial barrier, and the gut immune system. Gut permeability is reported to increase in sepsis and to play a key role in the development of multi-organ dysfunction. Therefore, gut permeability markers might have the potential to predict the risk of progression from sepsis to severe sepsis. The mechanisms leading to increased gut permeability are not completely clear, yet. Direct and indirect interactions of pathogens, hormonal imbalances, beta-adrenergic activity, hyperglycemia and cytokine activation as well as individual predisposition have been proposed. It seems that increased gut permeability is the common final pathway of a multitude of influencing factors.

Furthermore, the importance of gut microbiota composition has recently been recognized in several diseases; however, not much is known about the role of the microbiome in sepsis to date. Available data suggest, that disturbances in microbiome homeostasis are present in sepsis, but it is yet unknown if these changes are cause or consequence of sepsis. Changes in gut barrier and/or gut microbiota can lead to an increase in microbial products in circulation, contributing to (inadequate) activation and later "paralysis" of immune cells. It is not yet known if the gut microbiome of a patient in early stages of sepsis differs from the healthy microbiome or from the microbiome of a patient in late stages of sepsis. Also, the possibility to modulate the gut microbiome in early sepsis has not been studied yet.

A typical strategy to modulate the gut microbiome is the use of probiotic bacteria. In sepsis, the use of probiotics is well established for specific indications, such as necrotising enterocolitis in neonates, however, studies in adults are scarce. Therefore the aim of this study is to investigate if the ingestion of a multispecies probiotic in early sepsis is able to modulate gut microbiota and/or gut permeability and observe the clinical outcome of treated patients.

Conditions

Sepsis

Study Design

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

Study Groups

Probiotic

5 g of Winclove-607 containing Bifidobacterium bifidum W23, Bifidobacterium lactis W51, Enterococcus faecium W54, Lactobacillus acidophilus W37, Lactobacillus acidophilus W55, Lactobacillus paracasei W20, Lactobacillus plantarum W1, Lactobacillus plantarum W62, Lactobacillus rhamnosus W71, Lactobacillus salivarius W24 at a concentration of 1.1 x 109 cfu/g twice daily for the 4 weeks

Group Type: ACTIVE_COMPARATOR

Winclove 607

Intervention Type: DIETARY_SUPPLEMENT

multispecies probiotic

Placebo

a similar looking and tasting placebo without bacteria once daily for 4 weeks

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DIETARY_SUPPLEMENT

Placebo

Interventions

Winclove 607

multispecies probiotic

Intervention Type: DIETARY_SUPPLEMENT

Placebo

Placebo

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

• Participant is willing and able to give informed consent for participation in the study.
• Age above 18 years
• Sepsis as defined by the presence of a systemic inflammatory response syndrome (2 out of the four: elevated heart rate (tachycardia) >90 beats per minute at rest; body temperature either high (>100.4 F or 38 C) or low (<96.8 F or 36 C); increased respiratory rate of >20 breaths per minute or a reduced partial pressure of carbon dioxide (PaCO2) in arterial blood level; abnormal white blood cell count (>12,000 cells/µL or <4,000 cells/µL or >10% bands [an immature type of white blood cell]) and a known or suspected infection
• Blood cultures ordered by the attending physician

Exclusion Criteria

• Severe sepsis or septic shock as defined by the Surviving Sepsis Guidelines [1]
• Admission to any intensive care unit or intermediate care unit for any reason
• soluble urokinase plasminogen activator receptor (sUPAR) level at admission >9.15 ng/mL [19]
• Positive beta-D-glycan test
• Patients receiving (par)enteral nutrition
• Presence or suspicion of acute pancreatitis
• Inability to understand and sign an informed consent
• Pregnancy or women of childbearing age without adequate contraception
• Women who are breast-feeding
• Known malignancy or any other condition or circumstance, which, in the opinion of the investigator, would affect the patient's ability to participate in the protocol

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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 Graz

Graz, , Austria

Countries

Austria

Other Identifiers

26-496 ex 13/14

Identifier Type: -

Identifier Source: org_study_id