EndotoxemiaMISSION-2NCT02127749
The Role of the Gut Microbiota in the Systemic Immune Response During Human Endotoxemia
A study testing Endotoxin and Vancomycin, Metronidazole, Ciprofloxacin in people with Endotoxemia, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
Trial summary
The purpose of this study is to determine whether treatment with antibiotics, which harm the gut flora, causes the immune system to be less effective. Read more about this study
- Who is it for?
- Ages 18 to 35 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Endotoxemia
- What is being tested?
- Endotoxin and Vancomycin, Metronidazole, Ciprofloxacin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteNetherlands
- Study dates
- Jun 2014to Dec 2015
- 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 35 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy
- Male between 18 and 35 years of age
- Capable of giving written informed consent
- Chemistry panel without any clinically relevant abnormality
- Normal defecation pattern
Who cannot join
- Major illness in the past 3 months or any chronic medical illness
- History of any type of malignancy
- Past or current gastrointestinal disease
- Known positive test for hepatitis C antibody, hepatitis B surface antigen or HIV antibody 1 or 2
- Current or chronic history of liver disease
- Subject uses tobacco products
Show all 17Show fewer
- History, within 3 years, of drug abuse
- History of alcoholism
- Any clinically relevant abnormality on the 12-lead ECG
- The subject has received an investigational product within three months
- Use of prescription or non-prescription drugs
- Use of antibiotics within 12 months
- Known allergy to antibiotics
- Subject has difficultly in donating blood or accessibility of a vein in left or right arm.
- Subject has donated more than 350 mL of blood in last 3 months
- Difficulty swallowing pills
- Body mass index more than 28
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this study is to determine whether treatment with antibiotics, which harm the gut flora, causes the immune system to be less effective.
Read the detailed description
Rationale: Sepsis ranks among the top ten leading causes of death worldwide. Most nonsurvivors die in a state of immunosuppression. The gut microbiota exerts numerous beneficial functions in the host response against infections. Gut flora components express microorganism-associated molecular patterns (MAMPs) such as lipopolysaccharide (LPS), which are recognized by pattern recognition receptors (PRRs) expressed by neutrophils and macrophages. MAMPs from the intestinal microbiota constitutively translocate to the circulation and prime bone marrow derived neutrophils via PRRs. Antibiotic treatment, which is standard of care for all patients with sepsis, depletes the gut microbiota and leads to a diminished release of MAMPs and other bacteria derived products. This causes diminished priming of systemic immunity, which may attribute to sepsis associated immunosuppression and an increased susceptibility to invading bacteria.
Objective: To investigate the role of the gut microbiota in the systemic priming of immune effector cells during human endotoxemia
Study design: Randomized, between- and within-subject-controlled intervention study in human volunteers
Intervention: All subjects will receive lipopolysaccharide (endotoxin; 2 ng/kg bodyweight) intravenously to induce experimental endotoxemia. Eight subjects will be pretreated with broad spectrum antibiotics (ciprofloxacin, vancomycin, metronidazole) for seven days (washout period of 36 hours before endotoxemia), in order to deplete the gut microbiota. Blood and faeces will be sampled before, during and after endotoxemia.
- Conditions
- Endotoxemia
- Being tested
- Endotoxin, Vancomycin, Metronidazole, Ciprofloxacin
- Keywords
- antibiotics, gut microbiota, endotoxemia, innate immunity
- Medical subject headings
- Endotoxemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EndotoxinDrug
Also called LPS
Both groups will receive 2 ng/kg LPS (endotoxin) intravenously
Vancomycin, Metronidazole, CiprofloxacinDrug
ciprofloxacin 500mg 2 times per day, vancomycin 500mg 3 times per day metronidazole 500mg 3 times per day All together during 7 days
| Study group | Role | What they receive |
|---|---|---|
| Control | Experimental | Subjects are not pretreated with antibiotics Subjects receive 2 ng/kg endotoxin intravenously Receives: Drug: Endotoxin |
| Antibiotics | Experimental | Subjects are pretreated with broad-spectrum antibiotics: Vancomycin, Metronidazole, Ciprofloxacin Subjects receive 2 ng/kg endotoxin intravenously Receives: Drug: Endotoxin; Drug: Vancomycin, Metronidazole, Ciprofloxacin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cytokine production in blood
Measured: within 8 hours after LPS administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2014 (estimated)
- Study startJun 2014
- Primary completionDec 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for EndotoxemiaStudies of the same condition, open and under way.
- More trials run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)The 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, W.J. Wiersinga, MD, PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Investigators
- W. J. Wiersinga, MD, PhD, Principal investigator, Academic Medical Centre, Amsterdam
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02127749
- Sponsor's protocol ID
- NL45198.018.13
- Other IDs
- NL45198.018.13
- Acronym
- MISSION-2
- Status last verified
- Dec 2015
- First submitted
- 28 Apr 2014
- Last updated
- 30 Dec 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Haak BW, Lankelma JM, Hugenholtz F, Belzer C, de Vos WM, Wiersinga WJ. Long-term impact of oral vancomycin, ciprofloxacin and metronidazole on the gut microbiota in healthy humans. J Antimicrob Chemother. 2019 Mar 1;74(3):782-786. doi: 10.1093/jac/dky471.
PubMed 30418539Lankelma JM, Cranendonk DR, Belzer C, de Vos AF, de Vos WM, van der Poll T, Wiersinga WJ. Antibiotic-induced gut microbiota disruption during human endotoxemia: a randomised controlled study. Gut. 2017 Sep;66(9):1623-1630. doi: 10.1136/gutjnl-2016-312132. Epub 2016 Jun 15.
PubMed 27307305
Study at a glance
From the registry record, last updated by the sponsor on 30 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of the Gut Microbiota in the Systemic Immune Response During Human Endotoxemia
- ClinicalTrials.gov ID
- NCT02127749
- Acronym / sponsor ID
- MISSION-2 / NL45198.018.13
- Conditions
- Endotoxemia
- Keywords
- antibiotics, gut microbiota, endotoxemia, innate immunity
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)University, hospital or other
- Study start
- Jun 2014
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 1 May 2014 (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.
The purpose of this study is to determine whether treatment with antibiotics, which harm the gut flora, causes the immune system to be less effective.
Detailed description
Rationale: Sepsis ranks among the top ten leading causes of death worldwide. Most nonsurvivors die in a state of immunosuppression. The gut microbiota exerts numerous beneficial functions in the host response against infections. Gut flora components express microorganism-associated molecular patterns (MAMPs) such as lipopolysaccharide (LPS), which are recognized by pattern recognition receptors (PRRs) expressed by neutrophils and macrophages. MAMPs from the intestinal microbiota constitutively translocate to the circulation and prime bone marrow derived neutrophils via PRRs. Antibiotic treatment, which is standard of care for all patients with sepsis, depletes the gut microbiota and leads to a diminished release of MAMPs and other bacteria derived products. This causes diminished priming of systemic immunity, which may attribute to sepsis associated immunosuppression and an increased susceptibility to invading bacteria.
Objective: To investigate the role of the gut microbiota in the systemic priming of immune effector cells during human endotoxemia
Study design: Randomized, between- and within-subject-controlled intervention study in human volunteers
Intervention: All subjects will receive lipopolysaccharide (endotoxin; 2 ng/kg bodyweight) intravenously to induce experimental endotoxemia. Eight subjects will be pretreated with broad spectrum antibiotics (ciprofloxacin, vancomycin, metronidazole) for seven days (washout period of 36 hours before endotoxemia), in order to deplete the gut microbiota. Blood and faeces will be sampled before, during and after endotoxemia.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control | Experimental | Drug: EndotoxinSubjects are not pretreated with antibiotics Subjects receive 2 ng/kg endotoxin intravenously |
| Antibiotics | Experimental | Drug: Endotoxin, Drug: Vancomycin, Metronidazole, CiprofloxacinSubjects are pretreated with broad-spectrum antibiotics: Vancomycin, Metronidazole, Ciprofloxacin Subjects receive 2 ng/kg endotoxin intravenously |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Healthy
- Male between 18 and 35 years of age
- Capable of giving written informed consent
- Chemistry panel without any clinically relevant abnormality
- Normal defecation pattern
Key exclusion criteria (17 listed)
- Major illness in the past 3 months or any chronic medical illness
- History of any type of malignancy
- Past or current gastrointestinal disease
- Known positive test for hepatitis C antibody, hepatitis B surface antigen or HIV antibody 1 or 2
- Current or chronic history of liver disease
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 |
|---|---|---|
| EndotoxinAlso: LPSBoth groups will receive 2 ng/kg LPS (endotoxin) intravenously | Drug | Antibiotics, Control |
| Vancomycin, Metronidazole, Ciprofloxacinciprofloxacin 500mg 2 times per day, vancomycin 500mg 3 times per day metronidazole 500mg 3 times per day All together during 7 days | Drug | Antibiotics |
Primary outcome
Cytokine production in blood
Time frame: within 8 hours after LPS administration
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 30 Dec 2015.
- Derived from this study: PubMed 30418539Haak BW, Lankelma JM, Hugenholtz F, Belzer C, de Vos WM, Wiersinga WJ. Long-term impact of oral vancomycin, ciprofloxacin and metronidazole on the gut microbiota in healthy humans. J Antimicrob Chemother. 2019 Mar 1;74(3):782-786. doi: 10.1093/jac/dky471.
- Derived from this study: PubMed 27307305Lankelma JM, Cranendonk DR, Belzer C, de Vos AF, de Vos WM, van der Poll T, Wiersinga WJ. Antibiotic-induced gut microbiota disruption during human endotoxemia: a randomised controlled study. Gut. 2017 Sep;66(9):1623-1630. doi: 10.1136/gutjnl-2016-312132. Epub 2016 Jun 15.
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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.
W. J. Wiersinga, MD, PhD principal investigator
Academic Medical Centre, Amsterdam
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Endotoxin and Vancomycin, Metronidazole, Ciprofloxacin in people with Endotoxemia, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
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 5 inclusion and 17 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 30 Dec 2015. 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 Netherlands. 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. 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?
Cytokine production in blood (time frame: within 8 hours after LPS administration). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02127749, which also lists 2 linked publications.
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 30 Dec 2015.