Primary Objectives- To determine the effect of the heat plate on suction blisters in a LPS challenge modelSecondary Objectives- To evaluate the safety and tolerability of the heat plate added to the LPS challenge model;- To evaluate the correlation…
ID
Source
Brief title
Condition
- Epidermal and dermal conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
* 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 outcome
* 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
Background summary
Skin suction blisters (SSB) can be artificially induced to retrieve fluid and
cells directly from the skin. These blisters are induced by negative pressure
through a vacuum. Duration of blister formation variates, but in most cases
this takes between 1-2 hours. Once the blister is formed, fluid can be
harvested by fine needle aspiration or directly by using a pipet after
puncturing the blister. In most cases SSB are induced on the ventral side of
the forearm. The SSB model is proven to be effective in objectively evaluating
human immune responses.
The suction blister device at CHDR is from Electronic Diversities (USA) and is
designed with a heat plate in each suction chamber. The heat is provided by
incandescent lamps which are controlled by a temperature controller. This
temperature controller is set at 40 degrees Centigrade. The lamps radiate and
conduct their heat to the orifice plate and provide sight on the skin area
where the blister is formed.
At CHDR the suction blister device has been previously used for several studies
(among which CHDR1752A, CHDR1752B and CHDR1912). In these studies, the suction
blister device was used with the heat plate switched off. This was how it was
tested in the USA prior to the use in our studies. Therefore, the effect of
heat on endpoints like cytokine release and cellular responses is unknown. And,
since previous studies reported that heat has a positive effect on blister
formation and reduces blister formation time, it is interesting to determine if
heat influences these endpoints.
Lipopolysaccharide (LPS) is a pro-inflammatory substance found on the outer
cell membranes of Gram-negative bacteria. It protects these bacteria from
phagocytosis and lysis. LPS is recognized by Toll-like receptor (TLR) 4 in a
normal functioning immune system. Administration of LPS into healthy human
volunteers creates a model in which immune responses can be monitored and
influenced. LPS can be used for intravenous, inhaled, nasal and intradermal
administration. Intradermal administration creates a rapid, limited local
inflammatory reaction and allows detailed insight in the local immune response
(CHDR1752A and CHDR 1752B)
The aim of this study is to determine the influence of heat on blister
formation, including cytokine release and cellular responses, in an intradermal
LPS challenge model in healthy volunteers.
Study objective
Primary Objectives
- To determine the effect of the heat plate on suction blisters in a LPS
challenge model
Secondary Objectives
- To evaluate the safety and tolerability of the heat plate added to the LPS
challenge model;
- To evaluate the correlation between clinical measures, biophysical measures,
and cellular and cytokine responses.
- To evaluate skin perfusion and local microcirculation after blister formation
with laser speckle contrast imaging (LSCI) and sidestream dark field microscopy
(SDFM).
- To evaluate skin morphology.
- To evaluate skin barrier function
Study design
An interventional study to determine the effect of heat on skin suction
blisters after intradermal LPS injections.
Intervention
Subjects will receive in total two intradermal doses of LPS on the lower
forearms on day 1. The dose per injection is 5 ng
Study burden and risks
The overall aim of this study is to determine the effect of heat on cytokine
releases and cellular responses found in skin blister fluid in an LPS skin
challenge model in healthy volunteers. The skin inflammation model with LPS for
healthy volunteers has been proven to be safe and has been used in several
studies. No medical benefit can be expected from this study for the
participating subjects.
Zernikedreef 8
Leiden 2333CL
NL
Zernikedreef 8
Leiden 2333CL
NL
Listed location countries
Age
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
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
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL79323.056.21 |