Skin Inflammation and PK of Azithromycin (AZI_IMQ_LPS)

December 13, 2023 updated by: Markus Zeitlinger, Medical University of Vienna

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

This study will investigate the tissue distribution of azithromycin in healthy, artificially inflamed and actually infected tissue of humans.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Part A will employ a skin inflammation challenge based on either LPS or the imiquimod according to the results of Part 0 (i.e., the one showing the greater leucocyte infiltration). Azithromycin will be given in parallel once daily for 3 consecutive days. After the last application (i.e. day 3), two microdialysis probes will be placed in the inflamed subcutaneous tissue and one will be placed in the unmanipulated healthy subcutaneous fat. Hereafter, PK sampling and microdialysis of two thighs will be performed for two consecutive days. The investigators will isolate leukocytes from blood samples on day 3 to determine the average concentration of azithromycin in them. Biopsies from the unmanipulated and the challenged skin will be obtained on day 4.

Part B will involve patients with skin infections including erysipelas and cellulitis at their lower extremities. In contrast to Part A, only one microdialysis probe will be placed into the infected subcutaneous tissue and one into healthy, unaffected tissue. After three doses of azithromycin, pharmacokinetic sampling, leukocyte isolation, and microdialysis of the healthy thigh and the respective area of infection will be performed.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
36

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Pilot Cohort for Skin Inflammation
Testing skin inflammation
Diagnostic test: Biopsy
Skin punch biopsy
Other: Skin inflammation model
LPS- or imiquimod induced skin inflammation
Experimental: Azithromycin and Artificial Skin Inflammation
Investigating tissue PK of Azithromycin in artificially inflamed tissue
Other: Skin inflammation model
LPS- or imiquimod induced skin inflammation
Drug: Azithromycin
500 mg once daily for 3 days
Experimental: Azithromycin and Skin Infection
Investigating tissue PK of Azithromycin in actually infected tissue
Drug: Azithromycin
500 mg once daily for 3 days

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
Day 3
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.
Day 3
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.
Day 3
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.
Day 3
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.
Day 3
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.
Day 3

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Part 0-A: Safety and tolerability of inflammation models
Time Frame: Day 0-3

Data will be aggregated as:

  • number of participants with treatment-related local adverse events due to the inflammation models
  • number of participants with treatment-related systemic adverse events due to the inflammation models
Day 0-3
Part A-B: Safety and tolerability of azithromycin
Time Frame: Day 0-3

Data will be presented as:

  • number of participants with treatment-related systemic adverse events due to azithromycin
  • mean number of treatment-related systemic adverse events due to azithromycin per subject
Day 0-3

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Medical University of Vienna

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 27, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 13, 2023

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 14, 2023

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 14, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 13, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • Pro_AZI_IMQ_LPS

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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