Modulation of Gut Microbiota in Early Sepsis: A Pilot Study (MGM-sepsis)

March 27, 2018 updated by: Medical University of Graz

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
15

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Graz, Austria, 8036
        • Department of Internal Medicine, Medical University of Graz

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 100 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: 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
Dietary supplement: Winclove 607
multispecies probiotic
Placebo Comparator: Placebo
a similar looking and tasting placebo without bacteria once daily for 4 weeks
Dietary supplement: Placebo
Placebo

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Gut microbiota composition
Time Frame: 4 weeks
next generation sequencing
4 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
gut permeability
Time Frame: 4 weeks
enzyme linked immunosorbent assay
4 weeks
endotoxin
Time Frame: 4 weeks
limulus amoebocyte assay
4 weeks
soluble sepsis markers
Time Frame: 4 weeks
enzyme linked immunosorbent assay
4 weeks
neutrophil function
Time Frame: 4 weeks
flow cytometry
4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Medical University of Graz

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Vanessa Stadlbauer-Köllner, MD, Medical University of Graz

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 31, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 3, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 8, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 11, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 29, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 27, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 26-496 ex 13/14

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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