Validation of Imiquimod- and LPS-induced Skin Inflammation Models and Their Application in the Investigation of Azithromycin Concentration in Inflamed, Infected, and Healthy Subcutaneous Tissue
Trial Snapshot
- Phase
- Not Applicable
- Status
- Not yet recruiting
- Sponsor
- Medical University of Vienna
- Enrollment
- 36
- Primary Endpoint
- Part 0: Area under the curve (AUC) of azithromycin in artificially inflamed tissue
Study Overview
Brief Summary
This study will investigate the tissue distribution of azithromycin in healthy, artificially inflamed and actually infected tissue of humans.
Detailed Description
This single-center, prospective, open-label, adaptive, pharmacokinetic study will comprise three parts: Part 0a-c, Part A, and Part B.
Objectives: This study primarily aims to characterize and establish a new skin inflammation model using topically applied LPS. The secondary aim of this research is to deepen our understanding of the role of leukocytes as potential transport vehicles for macrolides and other antibiotics in humans.
Intervention: Part 0 will serve as a pilot experiment in healthy volunteers to validate the imiquimod and LPS challenge in a controlled design. The investigators will clinically assess the tolerability of increasing LPS doses and the already published design of the imiquimod challenge. In general, the investigators will perform the different designs of skin inflammation models using tape stripping and an occlusive 18-mm Finn chamber.
The inflammation will not only be clinically assessed but also objectively quantified using the imaging-based mobile phone application Scarletred®Vision. Considering these results, the investigators will again carry out the LPS and imiquimod challenge in healthy volunteers and additionally perform biopsies in Part 0c to collect specimens for flow cytometry. Thus, the investigators will be able to characterize the skin inflammation models at a cellular level. Using NGS, the investigators will also explore transcriptional changes within cell subset that are affected by the inflammation.
In Part 0c, the investigators will include 12 healthy volunteers and will perform in each subject three skin punch biopsies, including a negative control, IMQ-challenged skin and LPS-challenged skin. Using flow cytometry, the investigators will measure the infiltration of leukocytes subsets.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 55 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •• Men and women aged ≥18 and <55 years
- •BMI ≥18 and ≤30 kg/m2
- •Normal (or clinically irrelevant abnormal) findings in medical history and physical examination
- •Women with child-bearing potential: use of effective contraception
- •Laboratory parameters within the given reference range (or abnormal findings which are irrelevant for study purposes in the Investigator's opinion)
Exclusion Criteria
- •Known or suspected allergy to lipopolysaccharide, imiquimod, or sticking plasters
- •Only Part 0c: Known or suspected allergy to local anesthetics
- •History of severe allergic or anaphylactic reactions to any medication • Blood donation within the last 4 weeks before the study
- •Treatment with an investigational drug within three weeks before the study
- •Smoking of more than 5 cigarettes per day
- •Regular use of medication or abuse of alcohol
- •Use of any medication within one week before the study
- •Symptoms of a clinically relevant illness in the 3 months before the study
- •Liver or kidney dysfunction
- •Pregnancy
- •History of autoimmune diseases (especially psoriasis)
- •Other objections to participating in the study in the opinion of the Investigator
Arms & Interventions
Pilot Cohort for Skin Inflammation
Testing skin inflammation
Intervention: Biopsy (Diagnostic Test)
Pilot Cohort for Skin Inflammation
Testing skin inflammation
Intervention: Skin inflammation model (Other)
Azithromycin and Artificial Skin Inflammation
Investigating tissue PK of Azithromycin in artificially inflamed tissue
Intervention: Azithromycin (Drug)
Azithromycin and Artificial Skin Inflammation
Investigating tissue PK of Azithromycin in artificially inflamed tissue
Intervention: Skin inflammation model (Other)
Azithromycin and Skin Infection
Investigating tissue PK of Azithromycin in actually infected tissue
Intervention: Azithromycin (Drug)
Outcomes
Primary Outcomes
Part 0: Area under the curve (AUC) of azithromycin in artificially inflamed tissue
Time Frame: Day 3
The pharmacokinetic concentration-time profile in tissue will be assessed by microdialysis. Concentration-time profiles will be plotted. AUC and Cmax will be used as PK parameters.
Part 0: Maximum concentration (Cmax) of azithromycin in artificially inflamed tissue
Time Frame: Day 3
The pharmacokinetic concentration-time profile in tissue will be assessed by microdialysis. Concentration-time profiles will be plotted. AUC and Cmax will be used as PK parameters.
Part A: Area under the curve (AUC) Azithromycin in healthy and inflamed tissue
Time Frame: Day 3
The pharmacokinetic concentration-time profile in tissue will be assessed by microdialysis. Concentration-time profiles will be plotted. AUC and Cmax will be used as PK parameters.
Part A: Maximum concentration (Cmax) Azithromycin in healthy and inflamed tissue
Time Frame: Day 3
The pharmacokinetic concentration-time profile in tissue will be assessed by microdialysis. Concentration-time profiles will be plotted. AUC and Cmax will be used as PK parameters.
Part B: Maximum concentration (Cmax) of Azithromycin in healthy and infected tissue
Time Frame: Day 3
The pharmacokinetic concentration-time profile in tissue will be assessed by microdialysis. Concentration-time profiles will be plotted. AUC and Cmax will be used as PK parameters.
Part B: Area under the curve (AUC) of Azithromycin in healthy and infected tissue
Time Frame: Day 3
The pharmacokinetic concentration-time profile in tissue will be assessed by microdialysis. Concentration-time profiles will be plotted. AUC and Cmax will be used as PK parameters.
Secondary Outcomes
- Part 0-A: Safety and tolerability of inflammation models(Day 0-3)
- Part A-B: Safety and tolerability of azithromycin(Day 0-3)
Investigators
Markus Zeitlinger
MD
Medical University of Vienna