Clinical trial NCT03779360: Intradermal LPS and Antibiotics
Official title: Investigating Anti-inflammatory Effects of Topical Antibiotics in an LPS Skin Challenge Model
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Inflammation; Skin
Lead sponsor: Centre for Human Drug Research, Netherlands
Sponsor class: OTHER
Collaborators: name: Maruho Co., Ltd.
First posted: 2018-12-19
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: An interventional, open-label, comparator controlled study to investigate the immunomodulatory effects of erythromycin and clindamycin in an LPS skin challenge model in healthy volunteers.
Primary purpose: BASIC_SCIENCE

Brief summary: Erythromycin and clindamycin are believed to have anti-inflammatory aspects. This study investigates the possible anti-inflammatory effects of erythromycin and clindamycin.

Detailed description: Convincing mechanistic reports on the immunomodulatory action of erythromycin and clindamycin are scarce, rarely based on experiments in freshly isolated human immune cells, and potentially contradicting. Moreover, direct immunomodulatory effects of both antibiotics have never been demonstrated in vivo. The Centre for Human Drug Research Biomarker lab has studied in depth the immunomodulatory actions of erythromycin and clindamycin in vitro. These in vitro experiments on primary human immune cells demonstrated that both erythromycin and clindamycin are able to modulate the immune response of peripheral blood mononuclear cells upon stimulation with different immune triggers such as lipopolysaccharide (LPS) and polyI:C. In this current study the in vitro work will be translated to an in vivo study where it will be made into an intradermal LPS skin challenge model in healthy volunteers.

Eligibility criteria: Inclusion Criteria:

1. Healthy male or 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, 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.
5. Able to work with the eDiary app.

Exclusion Criteria:

1. Any disease associated with immune system impairment, including auto-immune diseases, HIV and transplantation patients;
2. Type 1 or type 2 diabetes mellitus;
3. Any vaccination within the last 3 months;
4. Family history of psoriasis;
5. History of pathological scar formation (keloid, hypertrophic scar);
6. Have any current and / or recurrent pathologically, clinical significant skin condition at the treatment area (i.e. atopic dermatitis);
7. Hypersensitivity for dermatological marker at screening;
8. Requirement of immunosuppressive or immunomodulatory medication within 30 days prior to enrollment or planned to use during the course of the study;
9. Excessive sun exposure or a tanning booth within 3 weeks of enrollment;
10. Participation in an investigational drug or device study within 3 months prior to screening or more than 4 times a year;
11. 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;
12. Current smoker and/or regular user of other nicotine-containing products (e.g., patches);
13. History of or current drug or substance abuse considered significant by the PI (or medically qualified designee), including a positive urine drug screen.

Primary outcomes:
measure: Change in perfusion by Laser speckle contrast imaging (LSCI)
timeFrame: Baseline, 3, 6, 10, 24 and 48 hours post LPS injection
measure: Change in erythema by Antera 3D camera and 2D camera
timeFrame: Baseline, 3, 6, 10, 24 and 48 hours post LPS injection
measure: Change in erythema by clinical evaluation (erythema grading scale)
timeFrame: Baseline, 3, 6, 10, 24 and 48 hours post LPS injection
measure: Change in temperature by thermography in celsius
timeFrame: Baseline, 3, 6, 10, 24 and 48 hours post LPS injection
measure: Change in skin microbiome
timeFrame: Baseline, 3, 6, 10, 24 and 48 hours post LPS injection
Secondary outcomes:
Other outcomes:
Locations:
city: Leiden
country: Netherlands
facility: Centre for Human Drug Research
state: Zuid-Holland
Study officials:
affiliation: Researc Director
name: Matthijs Moerland, PhD
role: PRINCIPAL_INVESTIGATOR
References: