The aim of this study is to characterize the inflammatory response upon intradermal LPS injection in healthy volunteers Not Applicable
Conditions
Interventions
LPS, purified lipopolysaccharide prepared from Escherichia Coli: 113: H10:K negative (U.S. Standard
Reference Endotoxin) will be used. This LPS batch is manufactured in the US by List
Sponsors
Centre for Human Drug Research
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Healthy male subjects, 18 to 45 years of age, inclusive. Healthy status is defined by absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead ECG, hematology, blood chemistry, blood serology and urinalysis 2. Body mass index (BMI) between 18 and 30 kg/m², inclusive, and with a minimum weight of 50 kg 3. Fitzpatrick skin type I-III (Caucasian) 4. Able and willing to give written informed consent and to comply with the study restrictions
Exclusion criteria
Exclusion criteria: 1. Any disease associated with immune system impairment, including auto-immune diseases, HIV and transplantation patients 2. Any vaccination within the last 3 months 3. Family history of psoriasis 4. History of pathological scar formation (keloid, hypertrophic scar) 5. Have any current and / or recurrent pathologically, clinical significant skin condition at the treatment area (i.e. atopic dermatitis) 6. Hypersensitivity for dermatological marker at screening 7. Requirement of immunosuppressive or immunomodulatory medication within 30 days prior to enrollment or planned to use during the course of the study 8. Tanning due to sunbathing, excessive sun exposure or a tanning booth within 3 weeks of enrollment 9. Participation in an investigational drug or device study within 3 months prior to screening or more than 4 times a year 10. Loss or donation of blood over 500 mL within three months prior to screening. Or the donation of plasma within 14 days prior to screening 11. Current smoker and/or regular user of other nicotine-containing products (e.g., patches) 12. History of or current drug or substance abuse considered significant by the PI (or medically qualified designee), including a positive urine drug screen
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| 1. Adverse events were monitored throughout the study 2. Blood pressure, heart rate and temperature were measured pre LPS/saline administration and at 3h 6h, 10h, 24h and 48h after administration 3. Local tolerance was measured pre LPS/saline administration and at 3h 6h, 10h, 24h and 48h after administration by using Numeric Rating Scale (NRS) for pruritus and pain for the injection site 4. Circulating cytokines and leukocytes were measured pre LPS/saline administration and at 3h 6h, 10h, 24h and 48h after administration | — |
Primary
| Measure | Time frame |
|---|---|
| 1. Non-invasive measures: 1.1. Skin Perfusion was measured by Laser speckle contrast imaging (LSCI) pre LPS/saline administration and at 3h 6h, 10h, 24h and 48h after administration 1.2. Erythema was measured by Antera 3D camera pre LPS/saline administration and at 3h 6h, 10h, 24h and 48h after administration 1.3. Erythema was scored by a physician (erythema grading scale) pre LPS/saline administration and at 3h 6h, 10h, 24h and 48h after administration 1.4. Temperature was measured by thermography pre LPS/saline administration and at 3h 6h, 10h, 24h and 48h after administration 2. Invasive measures: Skin punch biopsies were taken pre LPS/saline administration and at 3h 6h, 10h, 24h and 48h after administration and analyzed for the following: 2.1. Immunochemistry: Neutrophils, Monocytes/macrophages, CD4+ lymphocytes, CD8+ lymphocytes, CD1a+ dendritic cells CD19+ B cells 2.2. mRNA analysis by qPCR: IFN-gamma, IL10, IL1-beta, IL6, IL8, TNF, MXA 3. Suction blisters were raised pre LPS/saline administration and at 3h 6h, 10h, 24h and 48h after administration and analyzed for the following: 3.1. Flowcytometry: Neutrophils, classical monocytes, non-classical monocytes, intermediate monocytes, dendritic cells, NK cells, CD4 T cells, CD8 T cells, B cells. MSD (protein): IFN-gamma, IL10, IL1-beta, IL6, IL8, TNF | — |
Countries
Netherlands
Contacts
Public ContactMatthijs Moerland
Outcome results
None listed