The Role of the Microbiota in the Systemic Immune Response

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02340182

Acronym

MISSION-1

Enrollment

Registered

2015-01-16

Start date

2013-03-31

Completion date

2013-09-30

Last updated

2015-01-16

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy, Sepsis

Keywords

gut flora, antibiotics, systemic immune response, Volunteers

Brief 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 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.

Interventions

DRUGVancomycin

250mg 3dd2

DRUGCiprofloxacin

500mg 2dd1

DRUGMetronidazole

500mg 3dd1

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

BASIC_SCIENCE

Masking

NONE

Eligibility

Sex/Gender

MALE

Age

18 Years to 35 Years

Healthy volunteers

Yes

Inclusion criteria

* 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)

Exclusion criteria

* 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; * 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.

Design outcomes

Primary

Measure	Time frame	Description
Composite measure of Laboratory parameters for inflammatory responses.	up to 7 weeks	Ex vivo response of whole blood, isolated monocytes or neutrophils to lipopolysaccharide.

Other

Measure	Time frame
Side effects will be registered using a graded scale	up to week 7
A HITchip (human intestinal tract chip; 16S rRNA) analysis will be used to determine microbiome composition	up to week 7

Countries

Netherlands

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026