Monocyte Profiles in Critically Ill Patients With Pseudomonas Aeruginosa Sepsis (MIPSA)

• ClinicalTrials.gov Identifier: NCT03044223
• Recruitment Status: Unknown
• First Posted: February 6, 2017
• Last Update Posted: February 6, 2017
• Sponsor: University of Ulm
• Information provided by (Responsible Party): Manfred Weiss, University of Ulm

Study Description

Brief Summary:

The present study focuses on patients with Pseudomonas aeruginosa (PSA) sepsis. The aim of the present study is to find out whether the M1 (pro-inflammatory) or M2 (anti-inflammatory) phenotype predominates in blood monocytes in critically ill patients with PSA-sepsis, and whether the severity of sepsis and outcome is associated with distinct monocyte phenotype and function.

Condition or disease
Pseudomonas Infections; Pseudomonas Septicemia; Pseudomonas; Pneumonia; Pseudomonal Bacteraemia; Pseudomonas Urinary Tract Infection; Pseudomonas Gastrointestinal Tract Infection; Sepsis; Sepsis, Severe; Critically Ill

Detailed Description:

During bacterial related sepsis, one of the key playing cells are macrophages, monocytes and T-lymphocytes (Hotchkiss et al., 2003). Macrophages and monocytes are supposed to be essential for the septic reaction to Gram-negative bacteria (Hotchkiss et al. 2003). Generally, there are two dominant types of macrophages: the pro-inflammatory M1 macrophage and the anti-inflammatory M2 macrophage (Mantovani et al., 2006). Similar to this macrophage characteristics, monocytes can also be categorized into pro-or anti-inflammatory. These macrophage/monocyte phenotypes can be differentiated in vitro from freshly isolated human blood monocytes using either GM-CSF giving raise to M1 macrophage/monocyte or M-CSF resulting in M2 macrophage/monocyte (Mantovani et al., 2006; Neu et al., 2013). Brunialti et al. (2012) have already demonstrated that the population of antiinflammatory M2 monocytes in septic patients is bigger than the pro-inflammatory M1 population. However, the authors did not further analyze the underlying mechanisms of M2 polarization nor did they identify the sepsis-causing pathogens.

In the present study, monocytes and macrophages of patients with Pseudomonas aeruginosa (PSA) sepsis are characterized by their surface marker expression profile via flow cytometry and cytokine pattern by ELISA in vivo and after ex-vivo LPS stimulation. In addition, an ex-vivo model system for PSA induced sepsis is validated. Blood of critically ill patients in the ICU infected with PSA is sampled to isolate peripheral blood mononuclear cells (PBMCs). Blood monocytes are analyzed for surface marker expression to determine the relative proportions of M1 and M2 monocytes in these patients and in healthy controls by flow cytometry

Study Design

• Study Type: Observational
• Estimated Enrollment: 100 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Phenotypical Und Functional Characterization of Macrophages in Critically Ill Patients With Pseudomonas Aeruginosa Induced Sepsis
• Study Start Date: August 2014
• Estimated Primary Completion Date: November 2018
• Estimated Study Completion Date: December 2018

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

1. Monocyte surface marker expression in critically ill patients with Pseudomonas aeruginosa sepsis [ Time Frame: two years ]
   Monocyte type 1, type 2 surface marker expression

Secondary Outcome Measures :

1. Cytokine concentrations in serum and production after ex-vivo stimulation of isolated monocytes of critically ill patients with Pseudomonas aeruginosa sepsis with LPS [ Time Frame: four years ]
   IL-8 and IFN-gamma

Biospecimen Retention:   Samples Without DNA

blood, plasma

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 90 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

Critically ill patients with sepsis with microbiologically proven infection with Pseudomonas aeruginosa

Criteria

Inclusion Criteria:

• age > 18 years
• critically ill patients with sepsis
• microbiologically proven infection with Pseudomonas aeruginosa

Exclusion Criteria:

• life expectancy < 24 hours
• participation in other studies

Contacts and Locations

Contacts

Contact: Manfred Weiss, MD, MBA; +49 731 500 60226; manfred.weiss@uniklinik-ulm.de

Contact: Eberhard Barth, MD; +49 731 500 60050; eberhard.barth@uniklinik-ulm.de

Locations

Germany

Clinic of Anesthesiology; Recruiting

Ulm, Germany, 89070

Contact: Manfred Weiss, MD, MBA +49-(0)731-500-60226 manfred.weiss@uniklinik-ulm.de

Contact: Eberhard Barth, MD +49-(0)731-500-60050 eberhard.barth@uniklinik-ulm.de

Sub-Investigator: Eberhard Barth, MD

Sub-Investigator: Michael Goergieff, MD

Sub-Investigator: Hendrik Bracht, MD

Sub-Investigator: Florian Gebhard, MD

Sub-Investigator: Doris Henne-Bruns, MD

Sub-Investigator: Marc-Eric Halatsch, MD

Sub-Investigator: Karl-Heinz Orend, MD

Sub-Investigator: Andreas Essig, MD

Sub-Investigator: Christian Riedel, PhD

Principal Investigator: Anne Sedlag, Biochemist

Sponsors and Collaborators

University of Ulm

Investigators

• Principal Investigator: Manfred Weiss, MD, MBA; University Ulm, University Hospital Ulm
• Principal Investigator: Anne Sedlag, Biochemist; University Ulm, Institute of Microbiology and Biotechnology

More Information

Publications of Results:

Neu C, Sedlag A, Bayer C, Förster S, Crauwels P, Niess JH, van Zandbergen G, Frascaroli G, Riedel CU. CD14-dependent monocyte isolation enhances phagocytosis of listeria monocytogenes by proinflammatory, GM-CSF-derived macrophages. PLoS One. 2013 Jun 11;8(6):e66898. doi: 10.1371/journal.pone.0066898. Print 2013.

Other Publications:

Brunialti MK, Santos MC, Rigato O, Machado FR, Silva E, Salomao R. Increased percentages of T helper cells producing IL-17 and monocytes expressing markers of alternative activation in patients with sepsis. PLoS One. 2012;7(5):e37393. doi: 10.1371/journal.pone.0037393. Epub 2012 May 31.

Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. N Engl J Med. 2003 Jan 9;348(2):138-50. Review.

Mantovani A, Sica A, Locati M. New vistas on macrophage differentiation and activation. Eur J Immunol. 2007 Jan;37(1):14-6. Review.

• Responsible Party: Manfred Weiss, Professor, MD, University of Ulm
• ClinicalTrials.gov Identifier: NCT03044223
• Other Study ID Numbers: PSA_Sepsis_M_1_2
• First Posted: February 6, 2017
• Last Update Posted: February 6, 2017
• Last Verified: February 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Manfred Weiss, University of Ulm:

pseudomonas aeruginosa; critically ill patient; sepsis; monocyte; macrophage; cytokine; severity of disease

Additional relevant MeSH terms:

Infections; Communicable Diseases; Sepsis; Toxemia; Urinary Tract Infections; Bacteremia; Pseudomonas Infections; Critical Illness; Disease Attributes; Pathologic Processes; Systemic Inflammatory Response Syndrome; Inflammation; Urologic Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Negative Bacterial Infections