N.a. N.a.
Conditions
Interventions
Sponsors
Universiteit Leiden
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Signed informed consent. Male or female participants, 20 - 69 years of age In general, stable good health.
Exclusion criteria
Exclusion criteria: Loss or donation of blood over 500mL within three months prior to screening. Alcohol consumption in the 24 hours preceding the study visit, or not being in fasted state 4 hours preceding the study visit (water is allowed). Smoking in the 4 hours preceding the study visit. (A history of) any clinically significant medical condition, factor or abnormality that might interfere with study conduct or interpretation, as judged by the investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary endpoints Laboratory assessments covering, but not limited to: • Measurements of mitotoxicity and cytotoxicity by confocal imaging after stimulation of PBMCs for 72 hours by a set of 8 compounds with a concentration range (7 concentrations in total) targeting various stress pathways o Mitotoxicity measured by the Rhodamine123 intensity of the cells o Early apoptotic cells measured by the fraction of annexin V positive cells (%) o Late stage apoptotic cells measured by the fraction of propidium-iodide positive cells (%) • Activation scores of relevant gene networks after stimulation of PBMCs for 24 hours by a set of 8 compounds with a concentration range (7 concentrations in total) targeting various stress pathways o Dose-response computational modelling at the individual gene level o Calculation of the activation score of relevant gene networks representing each individual compound using the TXG-MAPr tool o Calculate benchmark concentrations and the maximum fold change activation of genes and networks for each donor and test compound o Calculate TDVF0.01 accounting for underestimation of the variance within the human population for each pathway | — |
Secondary
| Measure | Time frame |
|---|---|
| Exploratory endpoints Laboratory assessments covering, but not limited to: • Abundance of phosphorylated kinases of example given, but not limited to, CD69+ B-Cells, CD4+ T-cells. • Abundance of exposome-related compounds using, example given, but not limited to, analysis of the lipidomic and metabolomic profile | — |
Countries
Netherlands
Contacts
Public ContactM.M. Moerland
Centre for Human Drug Research
Outcome results
None listed