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

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

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.

Study Overview

• Status: Completed
• Conditions: Prosthetic Joint Infection; Surgical Site Infection; Prosthesis and Implants; Postoperative Wound Infection Deep Incisional Surgical Site
• Intervention / Treatment: Other: Photodynamic Therapy

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Zurich, Switzerland, 8091
    • University Hospital of Zurich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control group; Skin swab for culture in the groin for baseline; NO PDT; Skin antisepsis; Skin swab for culture
Experimental: Arm A (MAL group); 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; PDT with two different photosensitizers
Experimental: Arm B (Methylene Blue group); 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; PDT with two different photosensitizers

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Zurich

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2021
• Primary Completion (Actual): June 24, 2021
• Study Completion (Actual): June 24, 2021

Study Registration Dates

• First Submitted: October 21, 2020
• First Submitted That Met QC Criteria: November 4, 2020
• First Posted (Actual): November 5, 2020

Study Record Updates

• Last Update Posted (Actual): September 14, 2021
• Last Update Submitted That Met QC Criteria: September 7, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Disease Attributes; Infections; Communicable Diseases; Surgical Wound Infection; Wound Infection
• Other Study ID Numbers: 2020_PHOMIC-II

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