Influence of heat on skin suction blisters in a lipopolysaccharide (LPS) challenge model in healthy volunteers Not Applicable
Conditions
Interventions
All volunteers will receive two intradermal lipopolysaccharide (LPS, 5 ng) injections in both forearms. Six hours after LPS injection, blisters will be made on these sites and on two control sites (un
Sponsors
Centre for Human Drug Research
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Healthy male and female subjects, 18 to 45 years of age, inclusive. Healthy status is defined by the 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: 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. Or the donation of plasma within 14 days 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 |
|---|---|
| 1. Blister induction time and volume measured after formation of skin suction blisters at 6 h 2. Cellular and cytokine responses in blister exudate and epidermal sheet measured using flow cytometry and Meso Scale Discovery (MSD) at 6 h 3. Blister volume and wound healing parameters evaluated using imaging (2D and 3D) at 8 h and 3D also at 8 h 30 min 4. Redness of the skin measured using clinical erythema score at baseline and 6 h | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Pain measured using Numeric Rating Scale (NRS) pain score at 6 h and 8 h 2. Blood flow measured with basal blow through Laser Speckle Contrast Imaging (LSCI) at 8 h 30 min 3. Microcirculation measured by sidestream darkfield microscopy (SDFM) at 8 h 30 min 4. Qualitative assessment of dermoepidermal layer by Optical Coherence Tomography (OCT) at 8 h 30 m 5. Barrier status of the skin measured using transepidermal water loss (TEWL) at 8 h 30 m | — |
Countries
Netherlands
Outcome results
None listed