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

Official title

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

Overview

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

• 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.
• 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.

Primary outcome measures

• Wound Healing Trajectory Measured by Digital Planimetry [Time frame: Baseline, post-intervention Day 1, post-intervention Day 2, and approximately 7 days after intervention]

Secondary outcome measures (4)

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

Eligibility 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• OU Health - Burn Unit — Oklahoma City

Publications

• 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. PMID 19932449
• 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. PMID 15122361
• Wainwright M. Photodynamic antimicrobial chemotherapy (PACT). J Antimicrob Chemother. 1998 Jul;42(1):13-28. doi: 10.1093/jac/42.1.13. PMID 9700525
• 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. PMID 21949150

Identifiers

NCT: NCT07494773 · HSC19626P

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗