NCT05570643

The Effects of Human Endotoxemia on Functional Capacity of Hematopoietic Stem and Progenitor Cells

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 12 (actual)
• Sponsor: Radboud University Medical Center · Academic / Other
• Sex: Male
• Age: 18 Years – 35 Years
• Healthy volunteers: Accepted

Summary

We will investigate whether human endotoxemia induces changes in human bone marrow cells and their downstream effector cells. To comprehensively investigate underlying mechanisms behind functional and transcriptional changes in these cell types, we will use state-of-the-art systems biology techniques, including single cell transcriptomics (epi)genetics, and metabolomics.

Detailed description

In the present study, we want to further elucidate the mechanisms behind systemic inflammation and endotoxin tolerance in vivo in humans by focusing on functional changes in hematopoietic stem and progenitor cells. Healthy male volunteers will be challenged with endotoxin to evoke a transient systemic inflammatory response. To evaluate the responses over time, blood and bone marrow aspirates will be collected at multiple timepoints. To comprehensively investigate underlying mechanisms behind functional changes, we will use state-of-the-art systems biology techniques, including single cell transcriptomics, epigenetics (e..g. scATACseq), and metabolomic. As such, this study will yield a comprehensive insight into inflammatory signaling in the different compartments of the body and will thereby improve our understanding of systemic inflammation, endotoxin tolerance,and sepsis, possibly revealing new therapeutic targets to improve sepsis outcome.

Conditions

• Sepsis, Endotoxemia, Immunosuppression

Interventions

Type	Name	Description
DRUG	LPS	This is a non-investigational product. LPS is used as challenge agent to achieve a controlled inflammatory state.
DRUG	Placebo	Injection of NaCl 0.9%.

Timeline

• Start date: 2018-01-05
• Primary completion: 2018-06-28
• Completion: 2018-06-28
• First posted: 2022-10-06
• Last updated: 2022-10-06

Locations

1 site across 1 country: Netherlands