Intradermal LPS and Antibiotics

Center for Human Drug Research (CHDR)

Status: Completed

Conditions: Inflammation; Skin

Treatments: Drug: Prednisolone tablet (0.5mg/kg; parallel comparison):; Drug: Erythromycin 4% topical gel formulation:; Drug: Clobetasol propionate 0.05% topical formulation (crossover comparison):; Drug: Clindamycin 1% lotion formulation:; Other: Lipopolysaccharide

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03779360

CHDR1752-B

Details and patient eligibility

About

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

Full 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.

Enrollment: 32 patients

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Factorial Assignment

Masking: None (Open label)

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32 participants in 3 patient groups

Subjects 1-6

Active Comparator group

Description:

7 day treatment of erythromycin and clindamycin twice daily on indicated skin areas prior to Clobetasol treatment; randomized either on the left or right arm for 2 days.

Treatment:

Drug: Clindamycin 1% lotion formulation:

Drug: Erythromycin 4% topical gel formulation:

Drug: Clobetasol propionate 0.05% topical formulation (crossover comparison):

Subjects 7-24

Experimental group

Description:

7 day treatment of erythromycin and clindamycin twice daily on indicated skin area prior to 4 Lipopolysaccharide injections and Clobetasol treatment; randomized either on the left or right arm for 2 days.

Treatment:

Other: Lipopolysaccharide

Drug: Erythromycin 4% topical gel formulation:

Drug: Clobetasol propionate 0.05% topical formulation (crossover comparison):

Subjects 25-30

Active Comparator group

Description:

0.5mg/kg prednisolone two days prior to Lipopolysaccharide injections

Treatment:

Other: Lipopolysaccharide

Drug: Prednisolone tablet (0.5mg/kg; parallel comparison):