SepsisMGM-sepsisNCT02469571
Modulation of Gut Microbiota in Early Sepsis: A Pilot Study
A study testing Winclove 607 in people with Sepsis, run by Medical University of Graz at 1 site in Austria.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Sepsis
- What is being tested?
- Winclove 607
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 1 siteAustria
- Study dates
- 1 Sep 2015to 1 Mar 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
Austria1 site
Department of Internal Medicine, Medical University of Graz
Graz, 8036
About this study
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.
Read the 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
- Being tested
- Winclove 607, Placebo
- Medical subject headings
- Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Winclove 607Dietary supplement
multispecies probiotic
PlaceboDietary supplement
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Probiotic | Active comparator | 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 Receives: Dietary Supplement: Winclove 607 |
| Placebo | Placebo comparator | a similar looking and tasting placebo without bacteria once daily for 4 weeks Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Gut microbiota composition
next generation sequencing
Measured: 4 weeks
Secondary outcomes (4)
gut permeability
enzyme linked immunosorbent assay
Measured: 4 weeks
endotoxin
limulus amoebocyte assay
Measured: 4 weeks
soluble sepsis markers
enzyme linked immunosorbent assay
Measured: 4 weeks
neutrophil function
flow cytometry
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2015 (estimated)
- Study start1 Sep 2015
- Primary completion31 Jul 2016
- Study completion1 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SepsisStudies of the same condition, open and under way.
- More trials run by Medical University of GrazThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University of Graz
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Vanessa Stadlbauer-Köllner, MD, Principal investigator, Medical University of Graz
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02469571
- Sponsor's protocol ID
- 26-496 ex 13/14
- Acronym
- MGM-sepsis
- Status last verified
- Mar 2018
- First submitted
- 3 Jun 2015
- Last updated
- 29 Mar 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Modulation of Gut Microbiota in Early Sepsis: A Pilot Study
- ClinicalTrials.gov ID
- NCT02469571
- Acronym / sponsor ID
- MGM-sepsis / 26-496 ex 13/14
- Conditions
- Sepsis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Medical University of GrazUniversity, hospital or other
- Study start
- 1 Sep 2015 (actual)
- Primary completion
- 31 Jul 2016 (actual)
- Study completion
- 1 Mar 2018 (actual)
- First posted
- 11 Jun 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Probiotic | Active comparator | Dietary Supplement: Winclove 6075 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 |
| Placebo | Placebo comparator | Dietary Supplement: Placeboa similar looking and tasting placebo without bacteria once daily for 4 weeks |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Winclove 607multispecies probiotic | Dietary supplement | Probiotic |
| PlaceboPlacebo | Dietary supplement | Placebo |
Primary outcome
Gut microbiota composition
Time frame: 4 weeks
next generation sequencing
4 secondary outcomes
gut permeability
Time frame: 4 weeks
endotoxin
Time frame: 4 weeks
soluble sepsis markers
Time frame: 4 weeks
neutrophil function
Time frame: 4 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vanessa Stadlbauer-Köllner, MD principal investigator
Medical University of Graz
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Winclove 607 in people with Sepsis, run by Medical University of Graz at 1 site in Austria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Gut microbiota composition (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Mar 2018.