Violet-Blue Light Inactivation of Bacteria in Chronic Wounds
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
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 Design
Arms and Interventions
| 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.
|
Outcome Measures
Primary Outcome Measures
- Overall Common Terminology Criteria for Adverse Events, version 5.0, Nov 27, 2017 (CTCAE) [4 weeks]
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.
Secondary Outcome Measures
- Baseline Clinical Wound Assessment [Baseline, 1 week]
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.
- Clinical Wound Assessment [Pre-intervention, up to 3 weeks]
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 Clinical Wound Assessment [Follow Up, up to 4 weeks]
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.
- Numeric Rating Scale (1-10) [Post-intervention, up to 3 weeks]
Pain scale in relation to treatment. Higher scores indicate more pain.
- Wong Baker FACES (1-10) [Post-intervention, up to 3 weeks]
Visual Pain scale in relation to treatment. Higher scores indicate more pain.
- Investigator Questionnaire [4 weeks]
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.
- Patient Questionnaire [4 weeks]
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".
- Mean time of visit [For every visit, up to 4 weeks]
Total time for the visit will be measured in minutes.
- Mean time of Treatment Procedure [Post-intervention, up to 3 weeks]
For every treatment visit, time used for the treatment with the FlashHeal Device is measured. Time is measured in minutes.
- Baseline Mean Bacterial Load [1 week]
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 Mean Bacterial Load [Pre-intervention, up to 3 weeks]
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 Mean Bacterial Load [Post-intervention, up to 3 weeks]
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.
- Mean Bacterial Load at Follow Up [Follow up, up to 4 weeks]
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.
- Baseline Wound Fluid [Baseline, 1 Week]
Swab for wound fluid performed once every week using the Essen Rotary Technique, testing for 6-10 cytokines assessing the inflammatory microenvironment.
- Change from Baseline Wound Fluid Composition Week 1 to Week 2 [2 Weeks]
Swab for wound fluid performed once every week using the Essen Rotary Technique, testing for 6-10 cytokines assessing the inflammatory microenvironment.
- Change from Baseline Wound Fluid Composition Week 1 to Week 3 [3 Weeks]
Swab for wound fluid performed once every week using the Essen Rotary Technique, testing for 6-10 cytokines assessing the inflammatory microenvironment.
- Change from Baseline Wound Fluid Composition Week 1 to Week 4 [4 weeks]
Swab for wound fluid performed once every week using the Essen Rotary Technique, testing for 6-10 cytokines assessing the inflammatory microenvironment.
- Baseline Wound Size Week 1 [Baseline, week 1]
Clinical Photography is performed once every week. Hereafter the wound is analysed with the ImageJ software to calculate wound size in cm2.
- Change from Baseline Wound Size Week 1 to Week 2 [2 Weeks]
Clinical Photography is performed once every week. Hereafter the wound is analysed with the ImageJ software to calculate wound size in cm2.
- Change from Baseline Wound Size Week 1 to Week 3 [3 Weeks]
Clinical Photography is performed once every week. Hereafter the wound is analysed with the ImageJ software to calculate wound size in cm2.
- Change from Baseline Wound Size Week 1 to Week 4 [Follow Up, 4 weeks]
Clinical Photography is performed once every week. Hereafter the wound is analysed with the ImageJ software to calculate wound size in cm2.
- Common Terminology Criteria for Adverse Events, version 5.0, Nov 27, 2017 (CTCAE) [Post-intervention, 2 weeks]
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.
- Common Terminology Criteria for Adverse Events, version 5.0, Nov 27, 2017 (CTCAE) [30 minutes Post-intervention, 2 weeks]
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.
- Common Terminology Criteria for Adverse Events, version 5.0, Nov 27, 2017 (CTCAE) [24 hours Post-intervention, 2 weeks]
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.
- Common Terminology Criteria for Adverse Events, version 5.0, Nov 27, 2017 (CTCAE) [48 hours Post-intervention, 2 weeks]
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.
- Common Terminology Criteria for Adverse Events, version 5.0, Nov 27, 2017 (CTCAE) [120 hours Post-intervention, 2 weeks]
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.
- Common Terminology Criteria for Adverse Events, version 5.0, Nov 27, 2017 (CTCAE) [Follow Up, 4 weeks]
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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Men, women and non-binaries fulfilling all inclusion criteria
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Age >18 - Patients with a chronic wound defined > 6 weeks
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Wound Area > 1 cm and < 25 cm
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Patient can understand Danish
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Patient can comply with protocol
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Patient is fully informed about the study and has given informed consent
Exclusion Criteria:
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Clinical infection in the wound requiring systemic or local antibiotics
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Current intake of antibiotics or locally applied (within 7 days before baseline)
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Known or suspected cancer in the wound
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Previous Photodermatitis and/or Photosensitivity
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Previous Porphyria and/or hypersensitivity to porphyrins
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Known congenital or acquired immunodeficiency
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Newly adjusted or newly started systemic immunomodulate treatment >4 weeks
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Treatment with haemodialysis
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Dementia - Participating in other clinical wound healing studies in the last 30 days
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Judgement by the investigator that the patient is not suited for study participation
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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)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Danish Wound Healing Center, Bispebjerg Hospital | Copenhagen | Northwest | Denmark | 2400 |
Sponsors and Collaborators
- Bispebjerg Hospital
- Hvidovre University Hospital
- Rigshospitalet, Denmark
Investigators
- Principal Investigator: Frederik Plum, MD, Danish Wound Healing Center, Bispebjerg Hospital
Study Documents (Full-Text)
None provided.More Information
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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Violet-Blue-Light-Inactivation