Pseudomonas InfectionsMIPSANCT03044223
Monocyte Profiles in Critically Ill Patients With Pseudomonas Aeruginosa Sepsis
An observational study of Pseudomonas Infections and Pseudomonas Septicemia, run by University of Ulm at 1 site in Germany.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 90 yearsHealthy volunteers can take part
- Conditions the study is for
- Pseudomonas Infections, Pseudomonas Septicemia, Pseudomonas; Pneumonia
- How many people
- 100 participants
- Where
- 1 siteGermany
- Study dates
- Aug 2014to Dec 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Critically ill patients with sepsis with microbiologically proven infection with Pseudomonas aeruginosa
Who may be able to join
- age > 18 years
- critically ill patients with sepsis
- microbiologically proven infection with Pseudomonas aeruginosa
Who cannot join
- life expectancy < 24 hours
- participation in other studies
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Germany1 site, 1 recruiting
- Recruiting
Clinic of Anesthesiology
Ulm, 89070
Manfred Weiss, MD, MBA, +49-(0)731-500-60226, manfred.weiss@uniklinik-ulm.de
Eberhard Barth, MD, +49-(0)731-500-60050, eberhard.barth@uniklinik-ulm.de
About this study
Official title: Phenotypical Und Functional Characterization of Macrophages in Critically Ill Patients With Pseudomonas Aeruginosa Induced Sepsis
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
- Conditions
- Pseudomonas Infections, Pseudomonas Septicemia, Pseudomonas; Pneumonia, Pseudomonal Bacteraemia, Pseudomonas Urinary Tract Infection, Pseudomonas Gastrointestinal Tract Infection
- Keywords
- pseudomonas aeruginosa, critically ill patient, sepsis, monocyte, macrophage, cytokine, severity of disease
- Medical subject headings
- Pseudomonas Infections, Pneumonia, Sepsis, Critical Illness
What is being measured
The primary outcome is the main question the study is designed to answer.
Monocyte surface marker expression in critically ill patients with Pseudomonas aeruginosa sepsis
Monocyte type 1, type 2 surface marker expression
Measured: 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
Measured: four years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2017 (estimated)
- Study startAug 2014
- Primary completionNov 2025 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Pseudomonas InfectionsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Ulm
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Manfred Weiss, University of Ulm
- Investigators
- Manfred Weiss, MD, MBA, Principal investigator, University Ulm, University Hospital UlmAnne Sedlag, Biochemist, Principal investigator, University Ulm, Institute of Microbiology and Biotechnology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03044223
- Sponsor's protocol ID
- PSA_Sepsis_M_1_2
- Acronym
- MIPSA
- Status last verified
- Jan 2024
- First submitted
- 2 Feb 2017
- Last updated
- 17 Jan 2024
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
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 22693573Hotchkiss 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 12519925Mantovani 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 17183610Neu 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
Study at a glance
From the registry record, last updated by the sponsor on 17 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phenotypical Und Functional Characterization of Macrophages in Critically Ill Patients With Pseudomonas Aeruginosa Induced Sepsis
- ClinicalTrials.gov ID
- NCT03044223
- Acronym / sponsor ID
- MIPSA / PSA_Sepsis_M_1_2
- Conditions
- Pseudomonas Infections, Pseudomonas Septicemia, Pseudomonas; Pneumonia, Pseudomonal Bacteraemia, Pseudomonas Urinary Tract Infection, Pseudomonas Gastrointestinal Tract Infection
- Keywords
- pseudomonas aeruginosa, critically ill patient, sepsis, monocyte, macrophage, cytokine, severity of disease
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University of UlmUniversity, hospital or other
- Study start
- Aug 2014
- Primary completion
- Nov 2025 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 6 Feb 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Critically ill patients with sepsis with microbiologically proven infection with Pseudomonas aeruginosa
Key inclusion criteria (3 listed)
- age > 18 years
- critically ill patients with sepsis
- microbiologically proven infection with Pseudomonas aeruginosa
Key exclusion criteria (2 listed)
- life expectancy < 24 hours
- participation in other studies
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Monocyte surface marker expression in critically ill patients with Pseudomonas aeruginosa sepsis
Time frame: two years
Monocyte type 1, type 2 surface marker expression
1 secondary outcome
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jan 2024.
- Background: PubMed 22693573Brunialti 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.
- Background: PubMed 12519925Hotchkiss 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.
- Background: PubMed 17183610Mantovani 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.
- Results publication: PubMed 23776701Neu 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Manfred Weiss, MD, MBA principal investigator
University Ulm, University Hospital Ulm
Anne Sedlag, Biochemist principal investigator
University Ulm, Institute of Microbiology and Biotechnology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Pseudomonas Infections and Pseudomonas Septicemia, run by University of Ulm at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 17 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Manfred Weiss, MD, MBA (+49 731 500 60226, manfred.weiss@uniklinik-ulm.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Monocyte surface marker expression in critically ill patients with Pseudomonas aeruginosa sepsis (time frame: two years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03044223, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jan 2024.