The Role of the Gut Microbiota in the Systemic Immune Response During Human Endotoxemia (MISSION-2)

December 29, 2015 updated by: W.J. Wiersinga, MD, PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

16

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Amsterdam, Netherlands, 1105 AZ
        • Academic Medical Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 35 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Control
Subjects are not pretreated with antibiotics Subjects receive 2 ng/kg endotoxin intravenously
Drug: Endotoxin
Both groups will receive 2 ng/kg LPS (endotoxin) intravenously
Other Names:
  • LPS
Experimental: Antibiotics
Subjects are pretreated with broad-spectrum antibiotics: Vancomycin, Metronidazole, Ciprofloxacin Subjects receive 2 ng/kg endotoxin intravenously
Drug: Endotoxin
Both groups will receive 2 ng/kg LPS (endotoxin) intravenously
Other Names:
  • 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Cytokine production in blood
Time Frame: within 8 hours after LPS administration
within 8 hours after LPS administration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Investigators

  • Principal Investigator: W. J. Wiersinga, MD, PhD, Academic Medical Centre, Amsterdam

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2014

Primary Completion (Actual)

December 1, 2015

Study Completion (Actual)

December 1, 2015

Study Registration Dates

First Submitted

April 28, 2014

First Submitted That Met QC Criteria

April 30, 2014

First Posted (Estimate)

May 1, 2014

Study Record Updates

Last Update Posted (Estimate)

December 30, 2015

Last Update Submitted That Met QC Criteria

December 29, 2015

Last Verified

December 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NL45198.018.13 (Other Identifier: CCMO (Centrale Commissie voor Mensgebonden Onderzoek))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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