Intradermal LPS and Antibiotics

Not Applicable

Completed

• Conditions: Inflammation; Skin
• Interventions: Other: Lipopolysaccharide

• Registration Number: NCT03779360
• Lead Sponsor: Centre for Human Drug Research, Netherlands

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.

Study Timeline

• Study Start: 2018-10-12
• Study First Submitted: 2018-12-10
• Study First Submitted QC: 2018-12-17
• Study First Posted: 2018-12-19
• Primary Completion: 2019-02-23
• Study Completion: 2019-02-23
• Status Verified: 2021-08
• Last Update Submitted: 2021-08-02
• Last Update Posted: 2021-08-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 32

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Subjects 25-30	Lipopolysaccharide	0.5mg/kg prednisolone two days prior to Lipopolysaccharide injections
Subjects 7-24	Lipopolysaccharide	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.

Primary Outcome Measures

Name	Time	Method
Change in erythema by Antera 3D camera and 2D camera	Baseline, 3, 6, 10, 24 and 48 hours post LPS injection	Standardized photographs will be taken using the Antera camera (Antera 3D, Miravex, Ireland).
Change in temperature by thermography in celsius	Baseline, 3, 6, 10, 24 and 48 hours post LPS injection	Skin temperature will be measured using a thermal imaging camera.
Change in perfusion by Laser speckle contrast imaging (LSCI)	Baseline, 3, 6, 10, 24 and 48 hours post LPS injection	Cutaneous microcirculation between pre and post-dose will be assessed using the laser speckle imager.
Change in erythema by clinical evaluation (erythema grading scale)	Baseline, 3, 6, 10, 24 and 48 hours post LPS injection	At the specific time points pre and post dose the colour of the injected area is scored (erythema index), on a 4 point scale; normal, mild, moderate, severe.
Change in skin microbiome	Baseline, 3, 6, 10, 24 and 48 hours post LPS injection	Collection of skin culture samples is a non-invasive procedure where a sterile polyester flock tip per site is passed along the surface of treated and non-treated areas.; bacteria studied include but are not limited to: Acinetobacter Anaerococcus Corynebacterium Enhydrobacter Finegoldia Lactobacillus Micrococcus Paracoccus Peptoniphilus Prevotella Propionibacterium Staphylococcus Streptococcus

Trial Locations

Locations (1)

Centre for Human Drug Research; 🇳🇱 Leiden, Zuid-Holland, Netherlands