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Innate Immune Functions of Immature Neutrophils

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified February 2010 by University Hospital, Geneva.
Recruitment status was:  Recruiting
Sponsor:
ClinicalTrials.gov Identifier:
NCT01155674
First Posted: July 2, 2010
Last Update Posted: July 2, 2010
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by:
University Hospital, Geneva
  Purpose
Polymorphonuclear neutrophils, or granulocytes, are essential effector cells of the innate immune system against bacterial infections. Their role in sepsis has been long established as the primary phagocyte to clear the infectious process. In the early phase of sepsis, one observes a massive recruitment of immature neutrophils from the bone marrow into peripheral blood, the so-called "band forms" or "left shift cells". Despite the daily clinical use of neutrophil band forms count in the care of septic patients and their abundance in septic blood, no information exists on the fate of these cells, nor on their capacity to mount an efficient innate immune response. It is the goal of this proposal to study the fate and the innate immune functions of immature neutrophils obtained in patients with early septic shock. Immature neutrophils will be separated from mature neutrophils. The following functions will be studied ex vivo in mature vs. immature neutrophils from a series of patients with severe sepsis and septic shock: (1) surface expression of receptors of the innate immunity; (2) production of inflammatory mediators and reactive oxygen species in response to bacterial agonists; (3) chemotaxis; (4) phagocytosis of Gram-positive and Gram-negative bacteria; and (5) ex vivo viability (life span) and resistance to apoptosis. Importantly, the investigators have developed and mastered all in vitro assays and cell separation techniques necessary to address and answer these important questions. This project will undoubtedly shed light on the fate and function of a prominent leukocyte population circulating in patients with severe bacterial infections and sepsis.

Condition
Sepsis SIRS

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Innate Immune Functions of Immature Neutrophils

Resource links provided by NLM:


Further study details as provided by University Hospital, Geneva:

Primary Outcome Measures:
  • Innate immune functions of neutrophils [ Time Frame: 12 months ]
    • Surface expression of receptors of the innate immunity in immature vs. mature neutrophils.
    • Production by immature vs. mature neutrophils of inflammatory mediators and reactive oxygen species in response to bacterial agonists.
    • Chemotaxis of immature vs. mature neutrophils.
    • Phagocytosis of Gram-positive and Gram-negative bacteria by immature vs. mature neutrophils.
    • Ex vivo viability and resistance to apoptosis of immature vs. mature neutrophils.


Biospecimen Retention:   Samples Without DNA
No samples retained

Estimated Enrollment: 60
Study Start Date: May 2010
Estimated Study Completion Date: October 2011
Estimated Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Groups/Cohorts
Sepsis patients
Patients presenting sepsis
SIRS patients
Patients presenting with the systemic inflammatory response syndrome
Healthy subjects
Healthy blood donors

Detailed Description:

Objectives

  1. Primary objective: To determine the innate immune functions of immature neutrophils in comparison to those from mature neutrophils, sampled from patients with severe sepsis and sepsis shock and in control patients (trauma patients and healthy donors (only mature neutrophils in the latter case)
  2. Secondary objectives: To determine the fate and span life of immature neutrophils in comparison to mature neutrophils, sampled from patients with severe sepsis and sepsis shock and in control patients (trauma patients and healthy donors (only mature neutrophils in the latter case).

Inclusion criteria

  • Patients with severe sepsis or septic shock (according to ACCP/FCCM standard definitions) with > 5% immature neutrophils.
  • Patients with a noninfectious systemic inflammatory response syndrome (SIRS), e.g. patients with head trauma or multiple trauma with > 5% immature neutrophils.
  • Healthy donors

Exclusion criteria

  • Severe immunosuppression (e.g. HIV with < 200 CD4/mm3), treatment with glucocorticoids (> 300 mg hydrocortisone/day) or other immunosuppressive therapy
  • Neutropenia (neutrophils < 0.5 G/l).
  • Recent chemotherapy or administration of intravenous immunoglobulins within the last 4 weeks.

Endpoints

  • Surface expression of receptors of the innate immunity in immature vs. mature neutrophils.
  • Production by immature vs. mature neutrophils of inflammatory mediators and reactive oxygen species in response to bacterial agonists.
  • Chemotaxis of immature vs. mature neutrophils.
  • Phagocytosis of Gram-positive and Gram-negative bacteria by immature vs. mature neutrophils.
  • Ex vivo viability and resistance to apoptosis of immature vs. mature neutrophils.
  Eligibility

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
  • Patients with severe sepsis or septic shock
  • Patients with a noninfectious systemic inflammatory response syndrome (SIRS)
  • Healthy donors
Criteria

Inclusion Criteria:

  • Patients with severe sepsis or septic shock (according to ACCP/FCCM standard definitions) with > 5% immature neutrophils.
  • Patients with a noninfectious systemic inflammatory response syndrome (SIRS), e.g. patients with head trauma or multiple trauma with > 5% immature neutrophils.
  • Healthy donors

Exclusion Criteria:

  • Severe immunosuppression (e.g. HIV with < 200 CD4/mm3), treatment with glucocorticoids (> 300 mg hydrocortisone/day) or other immunosuppressive therapy
  • Neutropenia (neutrophils < 0.5 G/l).
  • Recent chemotherapy or administration of intravenous immunoglobulins within the last 4 weeks.
  Contacts and Locations
Information from the National Library of Medicine

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): NCT01155674


Contacts
Contact: Geneviève Drifte, MD genevieve.drifte@unige.ch

Locations
Switzerland
University Hospitals of Geneva, Intensive Care Recruiting
Geneva, Switzerland, 1211
Contact: Jerome Pugin, MD       jerome.pugin@unige.ch   
Sub-Investigator: Geneviève Drifte, MD         
Sponsors and Collaborators
University Hospital, Geneva
  More Information

Responsible Party: Professor Jérôme Pugin, University Hospitals of Geneva
ClinicalTrials.gov Identifier: NCT01155674     History of Changes
Other Study ID Numbers: CER 09-311
First Submitted: July 1, 2010
First Posted: July 2, 2010
Last Update Posted: July 2, 2010
Last Verified: February 2010

Keywords provided by University Hospital, Geneva:
Innate immunity
Neutrophils
Band forms