The effects of human endotoxemia on the functional capacity of hematopoietic stem and progenitor cells

The effects of human endotoxemia on the functional capacity of hematopoietic stem and progenitor cells - LPS-BM study

Status

Recruiting

Phases

Unknown

Study type

Interventional

Source

NL-OMON

Registry ID

NL-OMON45383

Enrollment

Registered

2017-07-17

Start date

2018-01-24

Completion date

Unknown

Last updated

2024-02-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

bacterial bloodstream infection Sepsis

Interventions

This study investigates the effects of experimental endotoxemia on the systemic inflammatory response and endotoxin tolerance in different compartments of the human body (bone marrow, blood, and lun

bone marrow

endotoxemia

endotoxin tolerance

HSPC

Eligibility

Age

18 Years to 64 Years

Inclusion criteria

Inclusion criteria: - Written informed consent - Age >=18 and

Exclusion criteria

Exclusion criteria: • Use of any medication • Smoking • History or signs of atopic syndrome (asthma, rhinitis with medication and/or eczema) • Known anaphylaxis or hypersensitivity to the non-investigational products or their excipients. • History or signs of hematological disease (bone marrow dysfunction): • Thrombocytopenia ( 160 or RR diastolic > 90) • Hypotension (defined as RR systolic 120 µmol/l) • Liver enzyme abnormalities (above 2x the upper limit of normal) • Medical history of any disease associated with immune deficiency • CRP > 20 mg/L, WBC > 12x109/L or

Design outcomes

Primary

Measure	Time frame
Characterization of human hematopoietic stem and progenitor cells before and after endotoxemia determined by: 1) Hematopoietic lineage differentiation (composition and cellularity) of the bone marrow compartment by FACS 2) Functional capacity by means of ex vivo cytokine release (including but not limited to IL-1β, TNF-a, IL-6, IL-10, IFN-γ) upon stimulation with PAMPs (e.g. LPS) and pathogens (e.g. S. aureus, C. albicans, M. tuberculosis, S. pneumonia)	—

Measure

Time frame

Characterization of human hematopoietic stem and progenitor cells before and after endotoxemia determined by: 1) Hematopoietic lineage differentiation (composition and cellularity) of the bone marrow compartment by FACS 2) Functional capacity by means of ex vivo cytokine release (including but not limited to IL-1β, TNF-a, IL-6, IL-10, IFN-γ) upon stimulation with PAMPs (e.g. LPS) and pathogens (e.g. S. aureus, C. albicans, M. tuberculosis, S. pneumonia)

—

Secondary

Measure	Time frame
• Ex vivo cytokine release of alveolar macrophages upon stimulation • Transcriptome of hematopoietic stem and progenitor cells, blood leukocytes, and alveolar macrophages • Epigenome of hematopoietic stem and progenitor cells, blood leukocytes, and alveolar macrophages • Cellular metabolism of hematopoietic stem and progenitor cells, blood leukocytes, and alveolar macrophages • Gene polymorphisms relating to innate immune function (e.g. autophagy ATG2b and ATG5 SNPs) • Life span and transit times of different subsets of leukocytes and their progenitors in human bone marrow (mitotic and post-mitotic pool) and the blood compartment • Circulating cytokine concentrations upon endotoxemia • Vital parameters during endotoxemia (mean arterial pressure, heart rate and temperature) • Illness score during endotoxemia	—

Measure

Time frame

• Ex vivo cytokine release of alveolar macrophages upon stimulation • Transcriptome of hematopoietic stem and progenitor cells, blood leukocytes, and alveolar macrophages • Epigenome of hematopoietic stem and progenitor cells, blood leukocytes, and alveolar macrophages • Cellular metabolism of hematopoietic stem and progenitor cells, blood leukocytes, and alveolar macrophages • Gene polymorphisms relating to innate immune function (e.g. autophagy ATG2b and ATG5 SNPs) • Life span and transit times of different subsets of leukocytes and their progenitors in human bone marrow (mitotic and post-mitotic pool) and the blood compartment • Circulating cytokine concentrations upon endotoxemia • Vital parameters during endotoxemia (mean arterial pressure, heart rate and temperature) • Illness score during endotoxemia

—

Countries

The Netherlands

Outcome results

None listed

Source: NL-OMON (via WHO ICTRP)