Effect of Photodynamic Therapy on Skin Microbiome. Single Center Study (PHOMIC-II)

Study Overview
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Brief Summary
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The overarching aim of this research project is to prevent orthopedic implant-associated infections. This study aims to investigate if PDT has an effect on bacterial skin colonization in order to improve skin antisepsis strategies for the prevention of surgical site infections.

Detailed Description
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Background: Periprosthetic joint infections are a feared complication after orthopedic surgery in particular in our increasing elderly population. These infections are usually difficult to treat, because microorganisms persist in biofilms on the orthopedic implant surface. Therefore, it would be desirable to prevent these infections. It is hypothesized that bacteria from the skin surface or dermis - such as Staphylococcus aureus, coagulase-negative staphylococci, or Cutibacterium sp. - are transmitted into the periimplant tissue during surgery. In an ongoing interdisciplinary study with the Orthopedic University Hospital Balgrist (data in preparation for publication), the investigators see that common skin antisepsis preparation is not effective to eliminate skin bacteria before surgery because they persist in sebaceous or sweat glands. Photodynamic therapy (PDT) has recently gained attention in the treatment of acne, a disease of the pilosebaceous unit, in which also Cutibacterium acnes is implicated. The PDT works here on the one hand through a long-lasting destruction of the sebaceous glands, and on the other hand due to anti-inflammatory and antimicrobial effects. In a previous pilot study, the investigators tested if skin antisepsis is improved with previous PDT with the photosensitizer-inducing prodrug 5% topical methyl aminolevulinate (MAL) on inguinal skin in 10 participants. The induced photosensitizer was protoporphyrin IX (Pp IX, 635 nm) activated by red light. The investigators showed a complete sterilization of colonizing skin bacteria at the same day after this treatment However, orthopedic surgeons are hesitant to perform an arthroplasty surgery after such a treatment due to skin erythema for a few days. The investigators are entirely convinced about this novel prevention concept but need to identify the photosensitizer with the ideal balance of antibactericidal effect versus skin irritation. Building upon the data they gathered, they will explore PDT with the Protoporphyrin IX inducing prodrug photosensitizer MAL and the photosensitizer Methylene blue with potentially less local side-effects (skin erythema). Primary outcome: Effect of photodynamic treatment with the photosensitizers Pp IX (MAL) and Methylene blue in combination with surgical antisepsis on bacterial skin colonization on the day of application and on day 1, 3, and 5 after PDT. Secondary outcome: Effect of PDT on the skin microbiome using molecular techniques.

Official Title
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Effects of Photodynamic Therapy on the Human Inguinal Skin Microbiome to Improve Antiseptic Effect - Pilot 2

Conditions
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Postoperative Wound Infection Deep Incisional Surgical Site, Prosthesis and Implants, Surgical Site Infection, Prosthetic Joint Infection

Intervention / Treatment
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* Other: Photodynamic Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and female participants ≥ 18 years who volunteer for the pilot study in which a routine photodynamic treatment in the Department of Dermatology will be applied and effect of skin colonization will be analyzed, and an informed consent is signed by the participant (after information about the project). Exclusion Criteria: Pregnant and lacting women Participants with inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc., Participants taking antibiotics in the 14 days prior to PDT or until follow-up at 21 days Participants who received oral retinoid therapy within the last 6 months Participants who received anti-inflammatory agents as NSAR within the 14 days prior and after the PDT Participants taking any photosensitizing drugs within 4 weeks prior to PDT Participants who had a history of photosensitivity disorder Fitzpatrick's skin phototype V-VI

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Intervention group with PDT Arm A will receive the photosensitizer MAL Arm B will receive Methylene blue as photosensitizer for the PDT.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A (MAL group)<br>Skin swab for culture in the groin for baseline PDT with 5% topical methyl aminolevulinate (MAL) as the prodrug for the photosensitizer Pp IX Skin swab for culture Skin antisepsis Skin swab for culture | Other: Photodynamic Therapy<br>* PDT with two different photosensitizers<br>|
| Experimental: Arm B (Methylene Blue group)<br>Skin swab for culture in the groin for baseline PDT with 0.01% methylene blue based photosensitizer (NF-031) Skin swab for culture Skin antisepsis Skin swab for culture | Other: Photodynamic Therapy<br>* PDT with two different photosensitizers<br>|
| No Intervention: Control group<br>Skin swab for culture in the groin for baseline NO PDT Skin antisepsis Skin swab for culture | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Culture results of skin swabs | Quantitative evaluatuation of bacterial density and species from skin swabs taken before PDT, immeadiately after PDT, and after after skin antisepsis using culture technique | within 10 days after PDT | 
| Culture results of skin swabs | Quantitative evaluatuation of bacterial density and species from skin swabs taken 1 day after PDT before and after skin antisepsis | within 11 days after PDT | 
| Culture results of skin swabs | Quantitative evaluatuation of bacterial density and species from skin swabs taken 3 days after PDT before and after skin antisepsis | within 13 days after PDT | 
| Culture results of skin swabs | Quantitative evaluatuation of bacterial density and species from skin swabs taken 5 days after PDT before and after skin antisepsis | within 15 days after PDT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Molecular results of skin swabs | Measurement of bacterial growth of colonizing bacteria and quantitative bacterial changes using an RNA based method | within 3 months |