LPS challenge Skin suction blister
Conditions
Interventions
Subjects will receive in total two intradermal doses of LPS on the lower
forearms on day 1. The dose per injection is 5 ng
Sponsors
Centre for Human Drug Research
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Healthy male and female 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, coagulation, blood serology and urinalysis; 2. Body mass index (BMI) between 18 and 32 kg/m2, inclusive, and with a minimum weight of 50 kg; 3. Fitzpatrick skin type I-III (Caucasian); 4. Subjects of childbearing potential must use effective contraception for the duration of the study; 5. Able and willing to give written informed consent and to comply with the study restrictions.
Exclusion criteria
Exclusion criteria: Eligible subjects must meet none of the following exclusion criteria at screening: 1. Any disease associated with immune system impairment, including auto-immune diseases, HIV and transplantation patients; 2. Any (medical) condition that would, in the opinion of the investigator, potentially compromise the safety or compliance of the patient or may preclude the patient*s successful completion of the clinical trial; 3. Any vaccination within the last month; COVID-19 vaccination is allowed up until 2 weeks before study day 1; 4. Have any current and / or recurrent pathologically, clinical significant skin condition at the treatment area (i.e. atopic dermatitis); including tattoos; 5. Hypersensitivity for dermatological marker at screening; 6. Requirement of immunosuppressive or immunomodulatory medication within 30 days prior to enrolment or planned to use during the course of the study; 7. Use of topical medication (prescription or over-the-counter [OTC]) within 30 days prior to day 1, or less than 5 half-lives (whichever is longer) on lower arms; 8. Excessive sun exposure or a tanning booth within 3 weeks of enrolment; 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; 11. Volunteers with clinically relevant infections; 12. Current nicotine use in excess of 5 cigarettes per day or unable to abstain from smoking during the course of the study (from screening till end of study); 13. History of or current drug or substance abuse considered significant by PI (or medically qualified designee), including a positive urine drug screen; 14. Covid-19 infection (with positive test result) within the last 4 weeks.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| * Clinical/biophysical measures: blister induction time, 2D and 3D images, blister volume, erythema by clinical evaluation (erythema grading scale) * Cellular and cytokine responses in blister exudate: o Cytokines and chemokines o Flow cytometry, immune cells including but not limited to: § Neutrophils § Monocytes/macrophages § CD4+ lymphocytes § CD8+ lymphocytes § CD56+ lymphocytes § CD1c dendritic cells | — |
Secondary
| Measure | Time frame |
|---|---|
| * NRS pain score * Blood flow as measured with basal flow through laser speckle contrast imaging (LSCI) * Microcirculation as measured by side-stream darkfield microscopy (SDFM). The following parameters will be analyzed: o Number of vessels, vessel density, perfused number of vessels, perfused vessel density * Qualitative assessment of dermo-epidermal layer * Transepidermal water loss | — |
Countries
Netherlands
Outcome results
None listed