Innate Immune Functions of Immature Neutrophils

• ClinicalTrials.gov Identifier: NCT01155674
• Recruitment Status: Unknown
• First Posted: July 2, 2010
• Last Update Posted: July 2, 2010
• Sponsor: University Hospital, Geneva
• Information provided by: University Hospital, Geneva

Tracking Information

• First Submitted Date: July 1, 2010
• First Posted Date: July 2, 2010
• Last Update Posted Date: July 2, 2010
• Study Start Date: May 2010
• Estimated Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 1, 2010)

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.

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Innate Immune Functions of Immature Neutrophils
• Official Title: Innate Immune Functions of Immature Neutrophils
• Brief Summary: 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.

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.

• Study Type: Observational
• Study Design: Observational Model: Case-Control; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples Without DNA

Description:

No samples retained

• 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

Condition

• Sepsis
• SIRS

• Intervention: Not Provided

Study Groups/Cohorts

• Sepsis patients
  Patients presenting sepsis
• SIRS patients
  Patients presenting with the systemic inflammatory response syndrome
• Healthy subjects
  Healthy blood donors

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: July 1, 2010): 60
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 2011
• Estimated Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Switzerland

Administrative Information

• NCT Number: NCT01155674
• Other Study ID Numbers: CER 09-311
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Professor Jérôme Pugin, University Hospitals of Geneva
• Study Sponsor: University Hospital, Geneva
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: University Hospital, Geneva
• Verification Date: February 2010