The Role of the Gut Microbiota in the Systemic Immune Response During Human Endotoxemia (MISSION-2)
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ClinicalTrials.gov Identifier: NCT02127749 |
Recruitment Status :
Completed
First Posted : May 1, 2014
Last Update Posted : December 30, 2015
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Condition or disease | Intervention/treatment | Phase |
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Endotoxemia | Drug: Endotoxin Drug: Vancomycin, Metronidazole, Ciprofloxacin | Not Applicable |
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 Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 16 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Basic Science |
Official Title: | The Role of the Gut Microbiota in the Systemic Immune Response During Human Endotoxemia |
Study Start Date : | June 2014 |
Actual Primary Completion Date : | December 2015 |
Actual Study Completion Date : | December 2015 |

Arm | Intervention/treatment |
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Experimental: Control
Subjects are not pretreated with antibiotics Subjects receive 2 ng/kg endotoxin intravenously
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Drug: Endotoxin
Both groups will receive 2 ng/kg LPS (endotoxin) intravenously
Other Name: LPS |
Experimental: Antibiotics
Subjects are pretreated with broad-spectrum antibiotics: Vancomycin, Metronidazole, Ciprofloxacin Subjects receive 2 ng/kg endotoxin intravenously
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Drug: Endotoxin
Both groups will receive 2 ng/kg LPS (endotoxin) intravenously
Other Name: LPS Drug: Vancomycin, Metronidazole, Ciprofloxacin ciprofloxacin 500mg 2 times per day, vancomycin 500mg 3 times per day metronidazole 500mg 3 times per day All together during 7 days |
- Cytokine production in blood [ Time Frame: within 8 hours after LPS administration ]

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Ages Eligible for Study: | 18 Years to 35 Years (Adult) |
Sexes Eligible for Study: | Male |
Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
- 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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02127749
Netherlands | |
Academic Medical Centre | |
Amsterdam, Netherlands, 1105 AZ |
Principal Investigator: | W. J. Wiersinga, MD, PhD | Academic Medical Centre, Amsterdam |
Responsible Party: | W.J. Wiersinga, MD, PhD, MD, PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) |
ClinicalTrials.gov Identifier: | NCT02127749 |
Other Study ID Numbers: |
NL45198.018.13 NL45198.018.13 ( Other Identifier: CCMO (Centrale Commissie voor Mensgebonden Onderzoek) ) |
First Posted: | May 1, 2014 Key Record Dates |
Last Update Posted: | December 30, 2015 |
Last Verified: | December 2015 |
antibiotics gut microbiota endotoxemia innate immunity |
Endotoxemia Bacteremia Sepsis Infections Toxemia Systemic Inflammatory Response Syndrome Inflammation Pathologic Processes Metronidazole Vancomycin Ciprofloxacin |
Anti-Infective Agents Anti-Bacterial Agents Antiprotozoal Agents Antiparasitic Agents Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Cytochrome P-450 CYP1A2 Inhibitors Cytochrome P-450 Enzyme Inhibitors |