The First In-Human Application of Continuous Low-Irradiance Phototherapy for Chronic Wounds: A Pilot Study
November 2023 | Volume 22 | Issue 11 | 1111 | Copyright © November 2023
Published online October 22, 2023
Shayan A. McGee MDa, Alexander B. White MDb, Patrick McMullan BSc, Thomas Serena MDd, Gary Rogers MDe
aDartmouth Hitchcock Medical Center, Department of Surgery, Lebanon, NH
bUniversity of North Carolina School of Medicine, Chapel Hill, NC
cThe University of Connecticut School of Medicine, Farmington, CT
dSerenaGroup Inc, Cambridge, MA
eTufts University School of Medicine, Boston, MA
Abstract
Background: Polymicrobial colonization and resultant biofilm formation significantly impair the process of wound healing. Stagnant tissue repair processes predispose patients to serious complications including systemic infection and limb amputation. Continuous Low-Irradiance Phototherapy (CLIP) is a novel therapeutic approach that delivers blue light at low irradiance for extended periods of time. Bench and preclinical work in the literature indicates that 405 nm light avoids thermal injury of healthy tissue, promotes a cytokine milieu favoring re-epithelialization and angiogenesis, and prevents bacterial and biofilm growth.
Objective: This is the first in-human evaluation of a technology that delivers continuous low-irradiance 405 nm light to chronic wounds. The objective of this study was to determine the safety, feasibility, and ergonomics of this device for the treatment of chronic wounds in adult human subjects. This was not a randomized study to determine device efficacy, although data on outcome were collected.
Methods: In this prospective observational pilot study, participants received the intervention 24 hours per day, 7 days per week, for 4 weeks. Cohort I was conducted from December 2018 to March 2019, with Cohorts II and III ongoing. 25 study participants were recruited by referral (Cohort I: 5 participants, Cohort II: 10 participants, Cohort III: 10 participants). Our primary endpoint was to monitor for safety, assess usability by nurses and physicians, and evaluate patient comfort. The secondary endpoint, although not randomized nor directly compared with standard intervention, was the percentage area reduction (PAR) of the wound.
Results: No adverse events or subject discomfort occurred with the CLIP intervention. The staff treating the study participants reported no ergonomic or compliance issues with the use of the device. The device received high scores in categories assessing practicality and ease of use. There was an average PAR of 29% (SD = 0.42).
Conclusion: This study serves as the first in-human evaluation of extended low-irradiance 405 nm light for chronic wound therapy. The device appears safe and easy to use and had no compliance issues in the outpatient setting. Study participants who received CLIP without interruption saw either partial or complete reduction in wound area.
J Drugs Dermatol. 2023;22(11):1111-1117 doi:10.36849/JDD.7206
INTRODUCTION
Chronic wounds are defined by a lack of progression through normal stages of tissue healing. These include diabetic foot ulcers (DFUs), venous leg ulcers (VLUs), and pressure ulcers (PrUs). These wounds take an average of 12 to 13 months to heal, and have a recurrence rate of 60% to 70%.1,2 Etiologies include prolonged venous insufficiency, peripheral arterial disease, hypertension, and neuropathy. Additionally, these wounds are often colonized with biofilm-producing microbes resistant to treatment with standard antibiotics. As a result, the tissue is subjected to excessive and prolonged inflammation, whilst unable to respond to normal epithelial migratory and proliferative stimuli. Stagnation of healing predisposes to severe complications including sepsis and amputation of affected limbs.
Biofilms present a significant obstacle in wound management. Comprised of microbial extracellular polymeric matrix, biofilms serve as a protective outer layer that facilitates evasion of endogenous immune defenses and prevents antibiotic therapies from effectively reaching the wound bed. Current clinical practice involves repeated wound debridement coupled with systemic or topical antibiotics. However, biofilms reform within hours of debridement, creating an environment that maintains long-term resistance to pharmaceutical agents. In response, these drugs are typically over-prescribed, which often leads to complications and dependence on third- and fourth-generation slow-release polymer antibiotics.3
