An interventional study of LPS and Placebo in Sepsis, Endotoxemia, Immunosuppression, sponsored by Radboud University Medical Center. Completed at 1 site in Netherlands. Open to male participants aged 18 Years to 35 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2022-10-06.
Sponsored by Radboud University Medical Center · Not applicable, Interventional, and Other
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.
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.
1,946 studies on the registry are indexed under Sepsis; 471 are open to participants now.
This study's enrollment of 12 is below the median of 105 across 918 interventional studies indexed under Sepsis.
Browse Sepsis studies →Radboud University Medical Center is the lead sponsor of 984 studies on the registry; 135 are open to participants now.
Of its 6 completed or terminated interventional studies of FDA-regulated products, 0 (0%) have results posted.
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Exclusion Criteria:
Healthy male volunteers that will receive an intravenous administration of LPS (2ng/kg) twice.
Drug: LPS
Healthy male volunteers that will receive an intravenous administration of placebo (NaCl 0.9%).
Drug: Placebo
This is a non-investigational product. LPS is used as challenge agent to achieve a controlled inflammatory state.
Also known as: Lipopolysaccharide (LPS from Escherichia coli Type O11), Endotoxin
Injection of NaCl 0.9%.
Also known as: NaCl
Change in function and transcriptional pathways
The change in function and transcriptional pathways (gene expression) of hematopoietic progenitor cells and blood leukocytes (using various functional assays and single cell RNAseq) following human endotoxemia.
Time frame: 15 days
Change in (Genome-wide) chromatin accessibility
The change in epigenomic profile (chromatin accessibility) of hematopoietic progenitor cells and blood leukocytes (using single cell ATACseq) following human endotoxemia.
Time frame: 15 days
Change in cellular metabolism
The change in cellular metabolism of hematopoietic progenitor cells and blood leukocytes (e.g. using Seahorse analyzer, CYTOF) following human endotoxemia.
Time frame: 15 days
Change in macrophage activity in the brain
To changes in tissue resident macrophages activity in the brain (assessed using 18F-DPA-714 labeling and PET examinations) following human endotoxemia.
Time frame: 15 days
Life-span of blood leukocytes during homeostasis
To assessment of the life-span and transit times of different subsets of leukocytes and their progenitors in the bone marrow of humans at homeostasis (using Deuterium labeling).
Time frame: 8 days
Life-span of blood leukocytes during endotoxemia
To determine the life-span and transit times of different subsets of leukocytes and their progenitors in the bone marrow of humans during human endotoxemia (using Deuterium labeling).
Time frame: 8 days
Plan to share: Yes — Single cell transcriptional/gene expression data will be shared.
Supporting information: Statistical analysis plan, Analytic code
Access criteria: Bulk RNA-seq and scRNA-seq data for this study can be downloaded from GEO database (https://www.ncbi.nlm.nih.gov/geo/) with the accession number: GSE212093. Codes used to perform the data analysis related to this study are available at https://github.com/fkeramati/LPS-SI
No publications or documents are linked to this record.
Ran from Jan 2018 to primary completion in Jun 2018, 5 months.
Of 246 non-industry interventional studies with no phase under Sepsis, half reached primary completion within 22 months of starting (the median), counting those still running; a quarter within 12 and three quarters within 44. This study's 5 months is below that.
Counting every sponsor, half of 267 studies reached it within 22 months; a quarter within 12 and three quarters within 43.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Sep 2022. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Escherichia coli lipopolysaccharide
Radboud University Medical Center →