Burns, Wound Infection
Conditions
Keywords
Photodynamic Therapy, Methylene Blue, Burn Wound Infection, Antimicrobial Photodynamic Therapy, Reactive Oxygen Species, Burn Wound Bacterial Burden
Brief summary
Burn wound infections remain a major source of morbidity in patients with thermal injuries and contribute to delayed healing, graft loss, and prolonged hospitalization. The emergence of antimicrobial-resistant organisms further complicates management and highlights the need for non-antibiotic antimicrobial strategies. Photodynamic therapy (PDT) is an antimicrobial approach that combines a photosensitizing agent with visible light to generate reactive oxygen species capable of killing bacteria. This randomized clinical trial will evaluate the safety and preliminary efficacy of methylene blue-mediated photodynamic therapy for the treatment of burn wound bacterial contamination. Participants receiving standard burn care will be randomized to receive either methylene blue-photodynamic therapy with blue light illumination or light therapy alone during routine dressing changes. Treatments will occur during two consecutive dressing changes. The primary objective is to determine whether methylene blue photodynamic therapy reduces bacterial burden in burn wounds compared with light therapy alone. Secondary outcomes include safety, tolerability, and effects on wound healing.
Detailed description
Burn wound infections remain a major complication following thermal injury and contribute to delayed wound healing, graft failure, prolonged hospitalization, and increased healthcare utilization. Management of burn wound bacterial contamination relies heavily on topical and systemic antibiotics. However, the increasing prevalence of antimicrobial-resistant organisms has created a need for alternative antimicrobial strategies that do not rely on conventional antibiotics. Photodynamic therapy (PDT) is a non-antibiotic antimicrobial approach that combines a photosensitizing compound with visible light to generate reactive oxygen species that rapidly kill bacteria through oxidative damage. Methylene blue is a well-characterized photosensitizer with known antimicrobial activity when activated by visible light. When exposed to appropriate wavelengths of light, methylene blue produces singlet oxygen and other reactive oxygen species that disrupt bacterial cell membranes and intracellular components. Photodynamic therapy has demonstrated broad antimicrobial activity in laboratory and preclinical studies, including activity against antibiotic-resistant organisms. The use of PDT for treatment of contaminated wounds offers the potential to reduce bacterial burden while minimizing the risk of antimicrobial resistance. This study is a randomized clinical trial designed to evaluate the safety and preliminary antimicrobial efficacy of methylene blue-mediated photodynamic therapy in burn wounds. Participants receiving standard burn care will be randomized to receive either methylene blue photodynamic therapy with blue light illumination or light therapy alone during routine dressing changes. Treatments will occur during two consecutive dressing changes. Methylene blue will be applied to the burn wound surface prior to illumination with a blue light source. The primary objective of this study is to determine whether methylene blue photodynamic therapy reduces bacterial burden in burn wounds compared with light therapy alone. Secondary objectives include evaluation of treatment safety, tolerability, and effects on wound healing. Results from this study will inform the feasibility and design of future trials evaluating photodynamic therapy as a novel adjunctive treatment for burn wound infection.
Interventions
DRUGMethylene Blue
Methylene blue will be applied topically to the burn wound surface prior to illumination. When activated by visible blue light, methylene blue acts as a photosensitizer that generates reactive oxygen species capable of killing bacteria. Methylene blue-mediated photodynamic therapy will be administered during two consecutive burn dressing changes.
DEVICEBlue Light Illumination
Burn wounds will be illuminated using a clinical blue light source during routine dressing changes. In the experimental arm, illumination will occur after topical application of methylene blue to activate photodynamic therapy. In the control arm, illumination will occur without methylene blue application.
Sponsors
University of Oklahoma
University of Rochester
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Due to the visible application of methylene blue during photodynamic therapy, blinding of participants and treating clinicians is not feasible. Outcome measures include quantitative bacterial cultures obtained from burn wounds.
Intervention model description
Participants will be randomized to one of two parallel groups. One group will receive methylene blue photodynamic therapy with blue light illumination during routine burn dressing changes, while the control group will receive blue light illumination alone. Treatments will be administered during two consecutive dressing changes while participants continue to receive standard burn care.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Inclusion * Age ≥18 * Partial- or full-thickness burn with partial-thickness component * Expected ≥7 days dressing changes * Able to consent Exclusion * Pregnancy or lactation o Pregnancy status will be determined by review of the medical record and, when clinically indicated per institutional policy, standard-of-care pregnancy testing. No additional pregnancy testing will be performed solely for research purposes. * Current use of SSRIs, SNRIs, MAO inhibitors, and other serotonergic agents * Inability to tolerate wound exposure * Inability to consent * Known glucose-6-phosphate dehydrogenase (G6PD) deficiency
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Wound Healing Trajectory Measured by Digital Planimetry | Baseline, post-intervention Day 1, post-intervention Day 2, and approximately 7 days after intervention | Burn wound healing will be quantified using standardized digital photography and planimetric image analysis to measure wound surface area over time. Images will be obtained using a calibrated imaging system with a measurement scale included in each image. Wound area measurements will be analyzed longitudinally to assess changes in wound size over the study period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Quantitative Bacterial Burden | Baseline, post-intervention Day 1, and post-intervention Day 2 | Quantitative bacterial burden will be measured using standardized surface wound swab cultures obtained during routine dressing changes. Bacterial load will be quantified using colony-forming unit (CFU) counts and analyzed as log₁₀ change from baseline to post-intervention measurements. |
| Intervention Feasibility | Intervention Day 1 and Intervention Day 2 | Feasibility will be assessed by the proportion of participants who successfully complete both intervention sessions during routine dressing changes without protocol deviation or early termination. |
| Participant-Reported Pain During Intervention | Immediately before and immediately after each intervention session (two sessions) | Pain will be assessed using a participant-reported 0-10 numeric rating scale obtained immediately before and immediately after each intervention session to evaluate treatment tolerability. |
| Treatment-Related Adverse Events | From first intervention through 7 days post-intervention | Adverse events potentially related to methylene blue application or visible light exposure will be recorded and graded according to CTCAE v5.0 criteria, including local wound reactions, unexpected pain escalation, or signs of systemic toxicity. |
Countries
United States
Contacts
CONTACTNicole A. Wilson, PhD, MD
PRINCIPAL_INVESTIGATORNicole A. Wilson, PhD, MD
University of Oklahoma Health Sciences
Outcome results
None listed