Topical Methylene Blue-Photodynamic Therapy (MB-PDT) for Burn Wound Infection

Topical Methylene Blue-Photodynamic Therapy (MB-PDT) for Burn Wound Infection: A Prospective Randomized Pilot Study

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Burns; Wound Infection
• Intervention / Treatment: Drug: Methylene Blue; Device: Blue Light Illumination

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.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Nicole A. Wilson, PhD, MD; Phone Number: 405-271-5922; Email: nicole-wilson@ou.edu

Study Locations

• United States
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • OU Health - Burn Unit
      • Contact: Nicole A. Wilson, PhD, MD; Phone Number: 405-271-5922; Email: nicole-wilson@ou.edu
      • Principal Investigator: Nicole A. Wilson, PhD, MD
      • Sub-Investigator: Arthur Grimes, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Methylene Blue Photodynamic Therapy; Participants in this arm will receive methylene blue-mediated photodynamic therapy during routine burn dressing changes. Methylene blue will be applied to the burn wound surface followed by illumination with blue light using a clinical light source. Treatments will be administered during two consecutive dressing changes in addition to standard burn care.	Drug: Methylene 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.; Other Names: Methylthioninium Chloride; Device: Blue 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.; Other Names: Bili-lamp; Blue Light Phototherapy
Active Comparator: Light Therapy Alone; Participants in this arm will receive blue light illumination during routine burn dressing changes without application of methylene blue. Treatments will be administered during two consecutive dressing changes in addition to standard burn care.	Device: Blue 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.; Other Names: Bili-lamp; Blue Light Phototherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Wound Healing Trajectory Measured by Digital Planimetry	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.	Baseline, post-intervention Day 1, post-intervention Day 2, and approximately 7 days after intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Quantitative Bacterial Burden	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.	Baseline, post-intervention Day 1, and post-intervention Day 2
Intervention Feasibility	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.	Intervention Day 1 and Intervention Day 2
Participant-Reported Pain During Intervention	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.	Immediately before and immediately after each intervention session (two sessions)
Treatment-Related Adverse Events	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.	From first intervention through 7 days post-intervention

Collaborators and Investigators

• Sponsor: University of Oklahoma
• Collaborators: University of Rochester
• Investigators: Principal Investigator: Nicole A. Wilson, PhD, MD, University of Oklahoma Health Sciences

Publications and helpful links

General Publications

• Bhutani VK; Committee on Fetus and Newborn; American Academy of Pediatrics. Phototherapy to prevent severe neonatal hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics. 2011 Oct;128(4):e1046-52. doi: 10.1542/peds.2011-1494. Epub 2011 Sep 26.
• Wainwright M. Photodynamic antimicrobial chemotherapy (PACT). J Antimicrob Chemother. 1998 Jul;42(1):13-28. doi: 10.1093/jac/42.1.13.
• Dai T, Huang YY, Hamblin MR. Photodynamic therapy for localized infections--state of the art. Photodiagnosis Photodyn Ther. 2009 Sep-Dec;6(3-4):170-88. doi: 10.1016/j.pdpdt.2009.10.008.
• Hamblin MR, Hasan T. Photodynamic therapy: a new antimicrobial approach to infectious disease? Photochem Photobiol Sci. 2004 May;3(5):436-50. doi: 10.1039/b311900a. Epub 2004 Feb 12.

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): May 31, 2028
• Study Completion (Estimated): May 31, 2028

Study Registration Dates

• First Submitted: March 17, 2026
• First Submitted That Met QC Criteria: March 20, 2026
• First Posted (Actual): March 27, 2026

Study Record Updates

• Last Update Posted (Actual): May 19, 2026
• Last Update Submitted That Met QC Criteria: May 14, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Photodynamic Therapy; Reactive Oxygen Species; Antimicrobial Photodynamic Therapy; Methylene Blue; Burn Wound Infection; Burn Wound Bacterial Burden
• Additional Relevant MeSH Terms: Wounds and Injuries; Infections; Burns; Wound Infection; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring; Phenothiazines; Methylene Blue
• Other Study ID Numbers: HSC19626P

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared. De-identified aggregate study results may be reported in scientific publications and presentations.

Drug and device information, study documents

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