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RecruitingNCT03044223MIPSAUpdated Jan 17, 2024

Monocyte Profiles in Critically Ill Patients With Pseudomonas Aeruginosa Sepsis

An observational study in Pseudomonas Infections, Pseudomonas Septicemia and Pseudomonas; Pneumonia, sponsored by University of Ulm. Recruiting at 1 site in Germany. Open to participants aged 18 Years to 90 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-01-17.

Sponsored by University of Ulm · Observational

Study type
Observational
Model
Cohort
Time perspective
Prospective
Enrollment
100
Ages
18 Years to 90 Years
Sex
All
01

Study 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.

Read the 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

02

Conditions studied

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

Keywords

  • pseudomonas aeruginosa
  • critically ill patient
  • sepsis
  • monocyte
  • macrophage
  • cytokine
  • severity of disease
03

Who can participate

Ages eligible
18 Years to 90 Years
Sexes eligible
All
Accepts healthy volunteers
Yes
Sampling method
Non-probability sample

Study population

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

Inclusion criteria

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

Exclusion criteria

Exclusion Criteria:

  • life expectancy \< 24 hours
  • participation in other studies
04

Study design

Observational model
Cohort
Time perspective
Prospective
Enrollment
100 participants (estimated)
Patient registry
No
Biospecimen retention
Samples without dna
05

What researchers measure

Primary outcomes

  1. Monocyte surface marker expression in critically ill patients with Pseudomonas aeruginosa sepsis

    Monocyte type 1, type 2 surface marker expression

    Time frame: two years

Secondary outcomes

  1. Cytokine concentrations in serum and production after ex-vivo stimulation of isolated monocytes of critically ill patients with Pseudomonas aeruginosa sepsis with LPS

    IL-8 and IFN-gamma

    Time frame: four years

06

Study locations

1 of 1 sites recruiting
  • Clinic of Anesthesiology
    Ulm, 89070, Germany
    • Manfred Weiss, MD, MBA · Contact · manfred.weiss@uniklinik-ulm.de · +49-(0)731-500-60226
    • Eberhard Barth, MD · Contact · eberhard.barth@uniklinik-ulm.de · +49-(0)731-500-60050
    • 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 · Sub investigator
    • Anne Sedlag, Biochemist · Principal investigator
    Recruiting
07

References and documents

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. PubMed 22693573 ↗
  • Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. N Engl J Med. 2003 Jan 9;348(2):138-50. doi: 10.1056/NEJMra021333. No abstract available. PubMed 12519925 ↗
  • Mantovani A, Sica A, Locati M. New vistas on macrophage differentiation and activation. Eur J Immunol. 2007 Jan;37(1):14-6. doi: 10.1002/eji.200636910. PubMed 17183610 ↗
  • Neu C, Sedlag A, Bayer C, Forster 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. PubMed 23776701 ↗

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT03044223
Lead sponsor
University of Ulm
Responsible party
Manfred Weiss (Professor, MD, University of Ulm) — Principal investigator
First posted
Feb 6, 2017
Start date
Aug 2014
Primary completion
Nov 2025 (estimated)
Completion
Dec 2026 (estimated)
Last update
Jan 17, 2024

Study contacts

Manfred Weiss, MD, MBA
Contact
manfred.weiss@uniklinik-ulm.de
+49 731 500 60226
Eberhard Barth, MD
Contact
eberhard.barth@uniklinik-ulm.de
+49 731 500 60050
Manfred Weiss, MD, MBA
principal investigator · University Ulm, University Hospital Ulm
Anne Sedlag, Biochemist
principal investigator · University Ulm, Institute of Microbiology and Biotechnology

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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