Violet-Blue Light Inactivation of Bacteria in Chronic Wounds

This four-week prospective clinical investigation will assess the safety and feasibility of a medical device without CE-marking. The medical device is a light-emitting-diode (LED) and is manufactured by VulCur MedTech Aps. Violet-blue light treatment is tested on a total of twenty-two patients with chronic wounds, divided into three groups, each group only receiving one dosage. Three dosages (low, medium and high) of violet-blue light treatment is tested. ID 1-7 are assigned to the low group, ID 8-15 are assigned to medium group and ID 16-22 are assigned to the high dosage group.

Study Overview

• Status: Recruiting
• Conditions: Wound Infection; Wound Heal; Phototherapy Complication; Photobiology; Light Treatment; Complications
• Intervention / Treatment: Device: Violet-Blue Light Treatment / FlashHeal Device

Detailed Description

This is as prospective safety and feasibility clinical trial investigating violet-blue light treatment on chronic wounds. This clinical trial runs from Q3 2022 - Q2 2023. Twenty-two patients with chronic wounds will be included (n = 22) for a study-period of four weeks. Week 1 includes one baseline visit. Through Week 2,3 and 4 treatment is given six times with a span of 24-72 hours between every treatment visit. Week 4 includes one follow up-visit. Patients entering the study are assigned to three light dosage groups (low, medium and high) according to their study ID. ID 1-7 are assigned to the low group, ID 8-15 are assigned to medium group and ID 16-22 are assigned to the high dosage group. Between each dosage of light, there will be an evaluation of primary and secondary endpoints by the sponsor and the principal investigator. Light dosage is only escalated should this evaluation be deemed safe. To determine treatment safety skin reactions are assessed after treatment at: 0 minutes, 30 minutes, 24 hours, 48 hours, 5th treatment visit and at follow-up. Adverse Events and Adverse Device Events are evaluated at every visit for every dosage, feasibility is evaluated at follow-up for both patient and investigator. This investigation complies with the Good Clinical Practice concerning medical devices and follows the ISO standard DS/EN 14 155 and the Declaration of Helsinki

• Study Type: Interventional
• Enrollment (Estimated): 22
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Frederik Plum, MD; Phone Number: +4529671247; Email: frederik.plum@regionh.dk
• Study Contact Backup: Name: Klaus Kirketerp-Møller, MD, Ph.D; Phone Number: +4540199087; Email: klaus.kirketerp-moeller.01@regionh.dk

Study Locations

• Denmark
  • Northwest
    • Copenhagen, Northwest, Denmark, 2400
      • Recruiting
      • Danish Wound Healing Center, Bispebjerg Hospital
      • Contact: Frederik Plum, MD; Phone Number: +4529671247; Email: frederik.plum@regionh.dk
      • Contact: Klaus Kirketerp-Møller, Consultant; Phone Number: +4540199087; Email: klaus.kirketerp-moeller.01@regionh.dk
      • Principal Investigator: Frederik Plum, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Men, women and non-binaries fulfilling all inclusion criteria
• Age >18 - Patients with a chronic wound defined > 6 weeks
• Wound Area > 1 cm and < 25 cm
• Patient can understand Danish
• Patient can comply with protocol
• Patient is fully informed about the study and has given informed consent

Exclusion Criteria:

• Clinical infection in the wound requiring systemic or local antibiotics
• Current intake of antibiotics or locally applied (within 7 days before baseline)
• Known or suspected cancer in the wound
• Previous Photodermatitis and/or Photosensitivity
• Previous Porphyria and/or hypersensitivity to porphyrins
• Known congenital or acquired immunodeficiency
• Newly adjusted or newly started systemic immunomodulate treatment >4 weeks
• Treatment with haemodialysis
• Dementia - Participating in other clinical wound healing studies in the last 30 days
• Judgement by the investigator that the patient is not suited for study participation
• Pregnant or breastfeeding women. (All fertile women who is not on safe contraception will need a negative pregnancy test performed at baseline. Safe contraception includes cobber and hormone Intra Uterine Device and Hormone anticonception drugs. Sterility is defined as have had surgical sterilisation and being postmenopausal)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low Exposure to Violet-Blue Light; ID 1-7 are assigned to the low dosage group	Device: Violet-Blue Light Treatment / FlashHeal Device; FlashHeal illuminates an area of 10 cm in diameter, located at 6-7 cm distance of the wound. Wounds larger than 10 cm in diameter, will receive enough treatments to cover the wound bed. To obtain full coverage the circular treatment area is relocated to cover the remaining wound field. The wavelength is 405 nm, Full Width Half Maximum at (FWHM) 400-415 nm. Device irradiances are adjusted to the total fluences required for the Low, Medium and High group, the treatment will last 15 minutes at all dosages. Light is emitted with 1000 Hz.
Experimental: Medium Exposure to Violet-Blue Light; ID 8-15 are assigned to the medium dosage group	Device: Violet-Blue Light Treatment / FlashHeal Device; FlashHeal illuminates an area of 10 cm in diameter, located at 6-7 cm distance of the wound. Wounds larger than 10 cm in diameter, will receive enough treatments to cover the wound bed. To obtain full coverage the circular treatment area is relocated to cover the remaining wound field. The wavelength is 405 nm, Full Width Half Maximum at (FWHM) 400-415 nm. Device irradiances are adjusted to the total fluences required for the Low, Medium and High group, the treatment will last 15 minutes at all dosages. Light is emitted with 1000 Hz.
Experimental: High Exposure to Violet-Blue Light; ID 16-22 are assigned to the high dosage group	Device: Violet-Blue Light Treatment / FlashHeal Device; FlashHeal illuminates an area of 10 cm in diameter, located at 6-7 cm distance of the wound. Wounds larger than 10 cm in diameter, will receive enough treatments to cover the wound bed. To obtain full coverage the circular treatment area is relocated to cover the remaining wound field. The wavelength is 405 nm, Full Width Half Maximum at (FWHM) 400-415 nm. Device irradiances are adjusted to the total fluences required for the Low, Medium and High group, the treatment will last 15 minutes at all dosages. Light is emitted with 1000 Hz.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Common Terminology Criteria for Adverse Events, version 5.0, Nov 27, 2017 (CTCAE)	Safety is measured as the absence of Adverse Events (AE) skin reactions. Adverse event skin reactions are assessed with the Common Terminology Criteria for Adverse Events U.S Department of Health and Human Services version 5.0, Nov 27, 2017 (CTCAE) adjusted to the skin. The violet-blue light treatment will be considered safe when less than 30 % have an overall CTCAE score larger than Grade 2 CTCAE. The overall CTCAE score for each patient is based on the one CTCAE score with the most severe grading.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline Clinical Wound Assessment	Evaluates wound symptoms (Exudate, necrosis, maceration, granulation, Oedema,) and skin symptoms (eczema, Erythema, Hyperpigmentation, Hypopogmentation, epthilializing) at a 4 step scale from none to mild, moderate, severe.	Baseline, 1 week
Clinical Wound Assessment	Evaluates wound symptoms (Exudate, necrosis, maceration, granulation, Oedema,) and skin symptoms (eczema, Erythema, Hyperpigmentation, Hypopogmentation, epthilializing) at a 4 step scale from none to mild, moderate, severe.	Pre-intervention, up to 3 weeks
Follow up Clinical Wound Assessment	Evaluates wound symptoms (Exudate, necrosis, maceration, granulation, Oedema,) and skin symptoms (eczema, Erythema, Hyperpigmentation, Hypopogmentation, epthilializing) at a 4 step scale from none to mild, moderate, severe.	Follow Up, up to 4 weeks
Numeric Rating Scale (1-10)	Pain scale in relation to treatment. Higher scores indicate more pain.	Post-intervention, up to 3 weeks
Wong Baker FACES (1-10)	Visual Pain scale in relation to treatment. Higher scores indicate more pain.	Post-intervention, up to 3 weeks
Investigator Questionnaire	Usability of the medical device is tested with the system usability Scale (SUS) testing 10 items on a 5 step scale from Strongly Disagree to Strongly Agree.	4 weeks
Patient Questionnaire	Evaluating Participant perceived; pain, time consumption and satisfaction through 20 items. Question 1-13 can be answered on a 5 step scale from "to a very high degree" till "not at all", including possibility to answer "dont know" and "not relevant". Item 14-20 can be answered with "Yes", "No" and "Dont Know".	4 weeks
Mean time of visit	Total time for the visit will be measured in minutes.	For every visit, up to 4 weeks
Mean time of Treatment Procedure	For every treatment visit, time used for the treatment with the FlashHeal Device is measured. Time is measured in minutes.	Post-intervention, up to 3 weeks
Baseline Mean Bacterial Load	E-Swabs, Essen Rotary Technique performed at baseline, follow-up and before and after treatment with FlashHeal Device. Bacteria will be cultured for aerobe and anaerobe species.	1 week
Pre-intervention Mean Bacterial Load	E-Swabs, Essen Rotary Technique performed at baseline, follow-up and before and after treatment with FlashHeal Device. Bacteria will be cultured for aerobe and anaerobe species.	Pre-intervention, up to 3 weeks
Post-intervention Mean Bacterial Load	E-Swabs, Essen Rotary Technique performed at baseline, follow-up and before and after treatment with FlashHeal Device. Bacteria will be cultured for aerobe and anaerobe species.	Post-intervention, up to 3 weeks
Mean Bacterial Load at Follow Up	E-Swabs, Essen Rotary Technique performed at baseline, follow-up and before and after treatment with FlashHeal Device. Bacteria will be cultured for aerobe and anaerobe species.	Follow up, up to 4 weeks
Baseline Wound Fluid	Swab for wound fluid performed once every week using the Essen Rotary Technique, testing for 6-10 cytokines assessing the inflammatory microenvironment.	Baseline, 1 Week
Change from Baseline Wound Fluid Composition Week 1 to Week 2	Swab for wound fluid performed once every week using the Essen Rotary Technique, testing for 6-10 cytokines assessing the inflammatory microenvironment.	2 Weeks
Change from Baseline Wound Fluid Composition Week 1 to Week 3	Swab for wound fluid performed once every week using the Essen Rotary Technique, testing for 6-10 cytokines assessing the inflammatory microenvironment.	3 Weeks
Change from Baseline Wound Fluid Composition Week 1 to Week 4	Swab for wound fluid performed once every week using the Essen Rotary Technique, testing for 6-10 cytokines assessing the inflammatory microenvironment.	4 weeks
Baseline Wound Size Week 1	Clinical Photography is performed once every week. Hereafter the wound is analysed with the ImageJ software to calculate wound size in cm2.	Baseline, week 1
Change from Baseline Wound Size Week 1 to Week 2	Clinical Photography is performed once every week. Hereafter the wound is analysed with the ImageJ software to calculate wound size in cm2.	2 Weeks
Change from Baseline Wound Size Week 1 to Week 3	Clinical Photography is performed once every week. Hereafter the wound is analysed with the ImageJ software to calculate wound size in cm2.	3 Weeks
Change from Baseline Wound Size Week 1 to Week 4	Clinical Photography is performed once every week. Hereafter the wound is analysed with the ImageJ software to calculate wound size in cm2.	Follow Up, 4 weeks
Common Terminology Criteria for Adverse Events, version 5.0, Nov 27, 2017 (CTCAE)	Safety is measured as the absence of Adverse Events (AE) skin reactions. Adverse event skin reactions are assessed with the Common Terminology Criteria for Adverse Events U.S Department of Health and Human Services version 5.0, Nov 27, 2017 (CTCAE). The CTCAE is adjusted to the skin.	Post-intervention, 2 weeks
Common Terminology Criteria for Adverse Events, version 5.0, Nov 27, 2017 (CTCAE)	Safety is measured as the absence of Adverse Events (AE) skin reactions. Adverse event skin reactions are assessed with the Common Terminology Criteria for Adverse Events U.S Department of Health and Human Services version 5.0, Nov 27, 2017 (CTCAE). The CTCAE is adjusted to the skin.	30 minutes Post-intervention, 2 weeks
Common Terminology Criteria for Adverse Events, version 5.0, Nov 27, 2017 (CTCAE)	Safety is measured as the absence of Adverse Events (AE) skin reactions. Adverse event skin reactions are assessed with the Common Terminology Criteria for Adverse Events U.S Department of Health and Human Services version 5.0, Nov 27, 2017 (CTCAE). The CTCAE is adjusted to the skin.	24 hours Post-intervention, 2 weeks
Common Terminology Criteria for Adverse Events, version 5.0, Nov 27, 2017 (CTCAE)	Safety is measured as the absence of Adverse Events (AE) skin reactions. Adverse event skin reactions are assessed with the Common Terminology Criteria for Adverse Events U.S Department of Health and Human Services version 5.0, Nov 27, 2017 (CTCAE). The CTCAE is adjusted to the skin.	48 hours Post-intervention, 2 weeks
Common Terminology Criteria for Adverse Events, version 5.0, Nov 27, 2017 (CTCAE)	Safety is measured as the absence of Adverse Events (AE) skin reactions. Adverse event skin reactions are assessed with the Common Terminology Criteria for Adverse Events U.S Department of Health and Human Services version 5.0, Nov 27, 2017 (CTCAE). The CTCAE is adjusted to the skin.	120 hours Post-intervention, 2 weeks
Common Terminology Criteria for Adverse Events, version 5.0, Nov 27, 2017 (CTCAE)	Safety is measured as the absence of Adverse Events (AE) skin reactions. Adverse event skin reactions are assessed with the Common Terminology Criteria for Adverse Events U.S Department of Health and Human Services version 5.0, Nov 27, 2017 (CTCAE). The CTCAE is adjusted to the skin.	Follow Up, 4 weeks

Collaborators and Investigators

• Sponsor: Bispebjerg Hospital
• Collaborators: Rigshospitalet, Denmark; Hvidovre University Hospital
• Investigators: Principal Investigator: Frederik Plum, MD, Danish Wound Healing Center, Bispebjerg Hospital

Publications and helpful links

General Publications

• Bjarnsholt T, Kirketerp-Moller K, Jensen PO, Madsen KG, Phipps R, Krogfelt K, Hoiby N, Givskov M. Why chronic wounds will not heal: a novel hypothesis. Wound Repair Regen. 2008 Jan-Feb;16(1):2-10. doi: 10.1111/j.1524-475X.2007.00283.x.
• Malone M, Bjarnsholt T, McBain AJ, James GA, Stoodley P, Leaper D, Tachi M, Schultz G, Swanson T, Wolcott RD. The prevalence of biofilms in chronic wounds: a systematic review and meta-analysis of published data. J Wound Care. 2017 Jan 2;26(1):20-25. doi: 10.12968/jowc.2017.26.1.20.
• Enwemeka CS. Antimicrobial blue light: an emerging alternative to antibiotics. Photomed Laser Surg. 2013 Nov;31(11):509-11. doi: 10.1089/pho.2013.9871. Epub 2013 Oct 18. No abstract available.
• Leanse LG, Dos Anjos C, Mushtaq S, Dai T. Antimicrobial blue light: A 'Magic Bullet' for the 21st century and beyond? Adv Drug Deliv Rev. 2022 Jan;180:114057. doi: 10.1016/j.addr.2021.114057. Epub 2021 Nov 18.
• Tomb RM, White TA, Coia JE, Anderson JG, MacGregor SJ, Maclean M. Review of the Comparative Susceptibility of Microbial Species to Photoinactivation Using 380-480 nm Violet-Blue Light. Photochem Photobiol. 2018 May;94(3):445-458. doi: 10.1111/php.12883. Epub 2018 Mar 31.
• Plattfaut I, Demir E, Fuchs PC, Schiefer JL, Sturmer EK, Bruning AKE, Oplander C. Characterization of Blue Light Treatment for Infected Wounds: Antibacterial Efficacy of 420, 455, and 480 nm Light-Emitting Diode Arrays Against Common Skin Pathogens Versus Blue Light-Induced Skin Cell Toxicity. Photobiomodul Photomed Laser Surg. 2021 May;39(5):339-348. doi: 10.1089/photob.2020.4932.
• Dai T, Gupta A, Huang YY, Yin R, Murray CK, Vrahas MS, Sherwood ME, Tegos GP, Hamblin MR. Blue light rescues mice from potentially fatal Pseudomonas aeruginosa burn infection: efficacy, safety, and mechanism of action. Antimicrob Agents Chemother. 2013 Mar;57(3):1238-45. doi: 10.1128/AAC.01652-12. Epub 2012 Dec 21.
• Wang Y, Wang Y, Wang Y, Murray CK, Hamblin MR, Hooper DC, Dai T. Antimicrobial blue light inactivation of pathogenic microbes: State of the art. Drug Resist Updat. 2017 Nov;33-35:1-22. doi: 10.1016/j.drup.2017.10.002. Epub 2017 Oct 13.
• Liebmann J, Born M, Kolb-Bachofen V. Blue-light irradiation regulates proliferation and differentiation in human skin cells. J Invest Dermatol. 2010 Jan;130(1):259-69. doi: 10.1038/jid.2009.194.

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2023
• Primary Completion (Estimated): March 30, 2024
• Study Completion (Estimated): March 30, 2024

Study Registration Dates

• First Submitted: January 12, 2023
• First Submitted That Met QC Criteria: February 20, 2023
• First Posted (Actual): February 22, 2023

Study Record Updates

• Last Update Posted (Actual): October 10, 2023
• Last Update Submitted That Met QC Criteria: October 9, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Safety; Blue Light; Violet Blue Light
• Additional Relevant MeSH Terms: Infections; Wounds and Injuries; Wound Infection
• Other Study ID Numbers: Violet-Blue-Light-Inactivation

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No