HealthyMISSION-1NCT02340182
The Role of the Microbiota in the Systemic Immune Response
A study testing Vancomycin, Ciprofloxacin and Metronidazole in people with Healthy and Sepsis, run by W.J. Wiersinga, MD, PhD at 1 site in Netherlands.
Trial summary
The objective of this study is to investigate the role of the gut microbiota in the systemic priming of immune effector cells. Twelve healthy male volunteers, 18-35 years of age, will be treated with broad spectrum antibiotics (ciprofloxacin, vancomycin, metronidazole) for seven days, in order to deplete the gut… Read more about this study
- Who is it for?
- Ages 18 to 35 years, men onlyHealthy volunteers can take part
- What is being tested?
- Vancomycin, Ciprofloxacin and Metronidazole
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteNetherlands
- Study dates
- Mar 2013to Sep 2013
- 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 and able to comply with the requirements and restrictions
- Chemistry panel without any clinically relevant abnormality
- Normal defecation pattern (defined as <3x/ day and >3x/week)
Who cannot join
- Major illness in the past 3 months or significant chronic medical illness;
- History of any type of malignancy;
- Past or current gastrointestinal disease which may influence the gut microbiota;
- Known positive test for hepatitis C antibody, hepatitis B surface antigen or HIV;
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities;
- Use of tobacco products;
Show all 14Show fewer
- History, within 3 years, of drug abuse;
- History of alcoholism and/or drinking more than 3 units of alcohol per day;
- The subject has received an investigational product within three months of day 1;
- Use of prescription or non-prescription drugs and herbal and dietary supplements within 6 months;
- Recent (< 12 months) use of antibiotics (any kind, except for dermal antibiotics);
- Allergy to antibiotics (any kind);
- Difficulty swallowing pills;
- Any other relevant issue.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Academisch Medisch Centrum
Amsterdam, North Holland, 1105 AZ
About this study
The objective of this study is to investigate the role of the gut microbiota in the systemic priming of immune effector cells. Twelve healthy male volunteers, 18-35 years of age, will be treated with broad spectrum antibiotics (ciprofloxacin, vancomycin, metronidazole) for seven days, in order to deplete the gut microbiota. Blood and faeces will be sampled before, 24 hours and 6 weeks after the 7-day period of antibiotics. Main study endpoints include laboratory parameters for inflammatory responses, functional assays (ex vivo stimulation assay) and gut microbiota composition.
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
Study design: Within-subject-controlled intervention study in human volunteers
Study population: Twelve healthy male subjects, 18-35 years of age
Intervention: All subjects will be treated with broad spectrum antibiotics (ciprofloxacin, vancomycin, metronidazole) for seven days, in order to deplete the gut microbiota. Blood and faeces will be sampled before, 24 hours and 6 weeks after the 7-day period of antibiotics.
Main study parameters/endpoints: Laboratory parameters for inflammatory responses, functional assays (ex vivo stimulation assay) and gut microbiota composition.
- Being tested
- Vancomycin, Ciprofloxacin, Metronidazole
- Keywords
- gut flora, antibiotics, systemic immune response, Volunteers
- Medical subject headings
- Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VancomycinDrug
250mg 3dd2
CiprofloxacinDrug
500mg 2dd1
MetronidazoleDrug
500mg 3dd1
| Study group | Role | What they receive |
|---|---|---|
| Antibiotics | Experimental | All volunteers will self-administer the following antibiotics for 7 consecutive days (concomitantly):
1. Vancomycin 250mg 3dd2;
2. Ciprofloxacin 500mg 2dd1;
3. Metronidazole 500mg 3dd1. Receives: Drug: Vancomycin; Drug: Ciprofloxacin; Drug: Metronidazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite measure of Laboratory parameters for inflammatory responses.
Ex vivo response of whole blood, isolated monocytes or neutrophils to lipopolysaccharide.
Measured: up to 7 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jan 2015 (estimated)
- Study startMar 2013
- Primary completionSep 2013
- Study completionSep 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies of the same condition, open and under way.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- W.J. Wiersinga, MD, PhD
- Sponsor type
- University, hospital or other
- Collaborators
- ZonMw: The Netherlands Organisation for Health Research and Development
- Responsible party
- Sponsor-investigator, W.J. Wiersinga, MD, PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Investigators
- Tom Van der Poll, MD, PhD, Principal investigator, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02340182
- Sponsor's protocol ID
- NL42072.018.12
- Other IDs
- 2012_283
- Acronym
- MISSION-1
- Status last verified
- Jan 2015
- First submitted
- 8 Jul 2013
- Last updated
- 16 Jan 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of the Microbiota in the Systemic Immune Response
- ClinicalTrials.gov ID
- NCT02340182
- Acronym / sponsor ID
- MISSION-1 / NL42072.018.12
- Keywords
- gut flora, antibiotics, systemic immune response, Volunteers
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- W.J. Wiersinga, MD, PhDUniversity, hospital or other
- Collaborators
- ZonMw: The Netherlands Organisation for Health Research and Development
- Study start
- Mar 2013
- Primary completion
- Sep 2013 (actual)
- Study completion
- Sep 2013 (actual)
- First posted
- 16 Jan 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.
The objective of this study is to investigate the role of the gut microbiota in the systemic priming of immune effector cells. Twelve healthy male volunteers, 18-35 years of age, will be treated with broad spectrum antibiotics (ciprofloxacin, vancomycin, metronidazole) for seven days, in order to deplete the gut microbiota. Blood and faeces will be sampled before, 24 hours and 6 weeks after the 7-day period of antibiotics. Main study endpoints include laboratory parameters for inflammatory responses, functional assays (ex vivo stimulation assay) and gut microbiota composition.
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
Study design: Within-subject-controlled intervention study in human volunteers
Study population: Twelve healthy male subjects, 18-35 years of age
Intervention: All subjects will be treated with broad spectrum antibiotics (ciprofloxacin, vancomycin, metronidazole) for seven days, in order to deplete the gut microbiota. Blood and faeces will be sampled before, 24 hours and 6 weeks after the 7-day period of antibiotics.
Main study parameters/endpoints: Laboratory parameters for inflammatory responses, functional assays (ex vivo stimulation assay) and gut microbiota composition.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Antibiotics | Experimental | Drug: Vancomycin, Drug: Ciprofloxacin, Drug: MetronidazoleAll volunteers will self-administer the following antibiotics for 7 consecutive days (concomitantly): 1. Vancomycin 250mg 3dd2; 2. Ciprofloxacin 500mg 2dd1; 3. Metronidazole 500mg 3dd1. |
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 and able to comply with the requirements and restrictions
- Chemistry panel without any clinically relevant abnormality
- Normal defecation pattern (defined as <3x/ day and >3x/week)
Key exclusion criteria (14 listed)
- Major illness in the past 3 months or significant chronic medical illness;
- History of any type of malignancy;
- Past or current gastrointestinal disease which may influence the gut microbiota;
- Known positive test for hepatitis C antibody, hepatitis B surface antigen or HIV;
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities;
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 |
|---|---|---|
| Vancomycin250mg 3dd2 | Drug | Antibiotics |
| Ciprofloxacin500mg 2dd1 | Drug | Antibiotics |
| Metronidazole500mg 3dd1 | Drug | Antibiotics |
Primary outcome
Composite measure of Laboratory parameters for inflammatory responses.
Time frame: up to 7 weeks
Ex vivo response of whole blood, isolated monocytes or neutrophils to lipopolysaccharide.
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 16 Jan 2015.
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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.
Tom Van der Poll, MD, PhD principal investigator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Vancomycin, Ciprofloxacin and Metronidazole in people with Healthy and Sepsis, run by W.J. Wiersinga, MD, PhD 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 14 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 16 Jan 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?
Composite measure of Laboratory parameters for inflammatory responses. (time frame: up to 7 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 16 Jan 2015.