Blue Light for Infections
Recruiting in Palo Alto (17 mi)
+1 other location
Overseen byMatthew R Rosengart, MD MPH
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Washington University School of Medicine
Disqualifiers: Traumatic brain injury, Blindness, Immunocompromised, others
No Placebo Group
Approved in 3 Jurisdictions
Trial Summary
What is the purpose of this trial?Our data suggest that modulating the characteristics of light carries the potential to modify the host response to injury and critical illness and thus, improve outcome. The ability to modify the host response to the stress of major operations and sepsis carries immense potential to improve patient care.
The primary purpose of this study is to determine if exposure to bright blue (442nm) enriched light, by comparison to ambient white fluorescent light, reduces the inflammatory response or organ dysfunction in patients undergoing 1) medical treatment for pneumonia, 2) a 2-stage arthroplasty for surgical management of a septic joint, 3) surgery for a necrotizing soft tissue infection (NSTI), and 4) surgery for an intraabdominal infection (e.g., diverticulitis).
We will expose participants to one of two (2) lighting conditions: 1) high illuminance (\~1700 lux,), blue (442nm) spectrum enriched light and 2) ambient white fluorescent light that provides the standard environmental lighting (\~300-400 lux, no predominant spectrum) of the hospital.
Both cohorts will be exposed to a 12 hours:12 hours light:dark cycle photoperiod. Those subjects assigned to blue light will be asked to shine this small portable blue enriched light on themselves from 0800 to 2000 for 3 days. At the transition from light to dark, the blue-enriched light is turned off, and additional blue wavelength light removed with an amber filter. Thus, the total period of intervention is 72 hours.
The outcome of interest is change in the inflammatory response after surgery for appendicitis or diverticulitis as measured by the following parameters: white blood cell count, heart rate, the development of abdominal abscess, serum cytokine concentrations.
The outcome of interest is change in the inflammatory response during pneumonia as measured by the following parameters: white blood cell count, heart rate, and serum cytokine concentrations.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.
What data supports the effectiveness of the treatment Blue Light Therapy for infections?
Research shows that blue light therapy can effectively kill a wide range of bacteria and fungi, including those resistant to drugs, by using specific wavelengths of light. It has been used successfully for acne and stomach infections, and studies suggest it could help treat wound infections by reducing bacteria and promoting healing.
12345Is blue light therapy safe for humans?
Blue light therapy is generally considered safe for humans, but some studies suggest that shorter wavelengths (like 420 nm) can cause skin cell damage at high doses. Longer wavelengths (above 455 nm) are less likely to be toxic to skin cells.
12678How is Blue Light Therapy different from other treatments for infections?
Blue Light Therapy is unique because it uses specific wavelengths of light to kill bacteria without the need for antibiotics, making it effective against both drug-sensitive and drug-resistant bacteria. It is less harmful to human cells compared to ultraviolet light and can target bacteria in both their free-floating and biofilm states, which are common in infections.
12359Eligibility Criteria
This trial is for adults over 18 who are undergoing surgery for appendicitis or diverticulitis, or receiving treatment for pneumonia. It's not suitable for individuals with traumatic brain injury, blindness, or those who have weakened immune systems.Inclusion Criteria
I am 18 or older and having surgery for appendicitis, diverticulitis, or being treated for pneumonia.
Exclusion Criteria
You have had a severe head injury, are blind, or have a weakened immune system.
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
1 week
1 visit (in-person)
Treatment
Participants are exposed to either blue light or ambient white light for 3 days following diagnosis or surgery
1 week
Daily monitoring during hospital stay
Follow-up
Participants are monitored for changes in inflammatory response and organ dysfunction
4 weeks
Weekly follow-up visits
Long-term Follow-up
Participants are monitored for long-term outcomes such as organ dysfunction and need for mechanical ventilation
28 days
Participant Groups
The study tests the effects of blue light exposure on patients' inflammatory responses after surgeries like appendectomy and colon resection, and during pneumonia treatment. The control group doesn't receive blue light to compare outcomes.
8Treatment groups
Experimental Treatment
Active Control
Group I: Pneumonia: Blue LightExperimental Treatment1 Intervention
a 12 hours:12 hours light:dark photoperiod cycle of bright (1700 lux) blue (peak 442 nm) enriched light for a total of 3 days after the initial diagnosis and informed consent. The photoperiod is 12 hours: 0800 to 2000. At the transition from light to dark (2000), the blue-enriched light is turned off, and additional blue wavelength light removed with an amber filter.
Group II: Necrotizing Soft Tissue Infection: Blue LightExperimental Treatment1 Intervention
a 12 hours:12 hours light:dark photoperiod cycle of bright (1700 lux) blue (peak 442 nm) enriched light for a total of 3 days after the initial diagnosis and informed consent. The photoperiod is 12 hours: 0800 to 2000. At the transition from light to dark (2000), the blue-enriched light is turned off, and additional blue wavelength light removed with an amber filter.
Group III: Intraabdominal infection: Blue LightExperimental Treatment1 Intervention
a 12 hours:12 hours light:dark photoperiod cycle of bright (1700 lux) blue (peak 442 nm) enriched light for a total of 3 days after the initial diagnosis and informed consent. The photoperiod is 12 hours: 0800 to 2000. At the transition from light to dark (2000), the blue-enriched light is turned off, and additional blue wavelength light removed with an amber filter.
Group IV: Infected Joint: Blue LightExperimental Treatment1 Intervention
a 12 hours:12 hours light:dark photoperiod cycle of bright (1700 lux) blue (peak 442 nm) enriched light for a total of 3 days after the initial diagnosis and informed consent. The photoperiod is 12 hours: 0800 to 2000. At the transition from light to dark (2000), the blue-enriched light is turned off, and additional blue wavelength light removed with an amber filter.
Group V: Necrotizing Soft Tissue Infection: Ambient LightActive Control1 Intervention
a 12 hours:12 hours light:dark photoperiod cycle of the standard white fluorescent ambient light of the hospital for a total of 3 days after the initial diagnosis and informed consent. The photoperiod is 12 hours: 0800 to 2000. At the transition from light to dark (2000), the ambient white lights are turned off.
Group VI: Intraabdominal infection: Ambient LightActive Control1 Intervention
a 12 hours:12 hours light:dark photoperiod cycle of the standard white fluorescent ambient light of the hospital for a total of 3 days after the initial diagnosis and informed consent. The photoperiod is 12 hours: 0800 to 2000. At the transition from light to dark (2000), the ambient white lights are turned off.
Group VII: Infected Joint: Ambient LightActive Control1 Intervention
a 12 hours:12 hours light:dark photoperiod cycle of the standard white fluorescent ambient light of the hospital for a total of 3 days after the initial diagnosis and informed consent. The photoperiod is 12 hours: 0800 to 2000. At the transition from light to dark (2000), the ambient white lights are turned off.
Group VIII: Pneumonia: Ambient LightActive Control1 Intervention
a 12 hours:12 hours light:dark photoperiod cycle of the standard white fluorescent ambient light of the hospital for a total of 3 days after the initial diagnosis and informed consent. The photoperiod is 12 hours: 0800 to 2000. At the transition from light to dark (2000), the ambient white lights are turned off.
Blue Light is already approved in European Union, United States, Canada for the following indications:
🇪🇺 Approved in European Union as Bright Light Therapy for:
- Seasonal Affective Disorder (SAD)
- Non-seasonal depression
- Jet lag
- Sleep disorders
🇺🇸 Approved in United States as Blue Light Therapy for:
- Seasonal Affective Disorder (SAD)
- Non-seasonal depression
- Circadian rhythm disorders
🇨🇦 Approved in Canada as Phototherapy for:
- Seasonal Affective Disorder (SAD)
- Non-seasonal depression
- Sleep disorders
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Barnes Jewish HospitalSaint Louis, MO
UPMC-Presbyterian HospitalPittsburgh, PA
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Who Is Running the Clinical Trial?
Washington University School of MedicineLead Sponsor
University of PittsburghLead Sponsor
National Institute of General Medical Sciences (NIGMS)Collaborator
References
Photoinactivation of Escherichia coli by 405 nm and 450 nm light-emitting diodes: Comparison of continuous wave and pulsed light. [2023]Antimicrobial blue light (ABL) therapy is one of the novel non-antibiotic approaches and recent studies showed the potential of pulsed ABL.
Antibacterial Activity of Blue Light against Nosocomial Wound Pathogens Growing Planktonically and as Mature Biofilms. [2022]The blue wavelengths within the visible light spectrum are intrinisically antimicrobial and can photodynamically inactivate the cells of a wide spectrum of bacteria (Gram positive and negative) and fungi. Furthermore, blue light is equally effective against both drug-sensitive and -resistant members of target species and is less detrimental to mammalian cells than is UV radiation. Blue light is currently used for treating acnes vulgaris and Helicobacter pylori infections; the utility for decontamination and treatment of wound infections is in its infancy. Furthermore, limited studies have been performed on bacterial biofilms, the key growth mode of bacteria involved in clinical infections. Here we report the findings of a multicenter in vitro study performed to assess the antimicrobial activity of 400-nm blue light against bacteria in both planktonic and biofilm growth modes. Blue light was tested against a panel of 34 bacterial isolates (clinical and type strains) comprising Acinetobacter baumannii, Enterobacter cloacae, Stenotrophomonas maltophilia, Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Enterococcus faecium, Klebsiella pneumoniae, and Elizabethkingia meningoseptica All planktonic-phase bacteria were susceptible to blue light treatment, with the majority (71%) demonstrating a ≥5-log10 decrease in viability after 15 to 30 min of exposure (54 J/cm(2) to 108 J/cm(2)). Bacterial biofilms were also highly susceptible to blue light, with significant reduction in seeding observed for all isolates at all levels of exposure. These results warrant further investigation of blue light as a novel decontamination strategy for the nosocomial environment, as well as additional wider decontamination applications.
Phototherapy of Pseudomonas aeruginosa-Infected Wounds: Preclinical Evaluation of Antimicrobial Blue Light (450-460 nm) Using In Vitro Assays and a Human Wound Skin Model. [2022]Objective: To determine effective treatment strategies against bacterial infections of burn wounds with Pseudomonas aeruginosa, we tested different treatment regimens with antibacterial blue light (BL). Background: Infections of burn wounds are serious complications and require effective and pathogen-specific therapy. Hereby, infections caused by P. aeruginosa pose a particular challenge in clinical practice due to its resistance to many antibiotics and topical antiseptics. Methods: LED-based light sources (450-460 nm) with different intensities and treatment times were used. Antibacterial effects against P. aeruginosa were determined by colony-forming unit (CFU) assays, human skin wound models, and fluorescence imaging. Results: In suspension assays, BL (2 h, 40 mW/cm2, 288 J/cm2) reduced bacterial number (>5 log10 CFU/mL). Applying 144 J/cm2, using 40 mW/cm2 for 1 h was more effective (>4 log10 CFU) than using 20 mW/cm2 for 2 h (>1.5 log10 CFU). BL with low irradiance (24 h, 3.5 mW/cm2, 300 J/cm2) only revealed bacterial reduction in thin bacteria-containing medium layers. In infected in vitro skin wounds only BL irradiation (2 h, 40 mW/cm2, 288 J/cm2) exerted a significant antimicrobial efficacy (2.94 log10 CFU/mL). Conclusions: BL treatment may be an effective therapy for P. aeruginosa-infected wounds to avoid radical surgical debridement. However, a significant antibacterial efficacy can only be achieved with higher irradiances and longer treatment times (min. 40 mW/cm2; >1 h), which cannot be easily integrated into regular clinical treatment protocols, for example, during a dressing change. Further studies are necessary to establish BL therapy for infected burns among tissue compatibility and interactions with previous therapeutic agents.
Application of 460 nm visible light for the elimination of Candida albicans in vitro and in vivo. [2018]The aim of the present study was to investigate the eradicating effects of 460 nm blue light (BL) on Candida albicans in vitro and in C. albicans‑infected skin wounds in a mouse model. In the present study, the antifungal effects of irradiation with BL on C. albicans in vitro and in vivo were investigated. C. albicans colonies and cell numbers were investigated using the spread plate method and flow cytometry respectively following treatment with BL irradiation. In order to determine whether BL can eradicate C. albicans cells within biofilms, an in vitro C. albicans biofilm model was established, and the effect of BL was subsequently investigated using a confocal laser scanning microscope and a Live/Dead staining kit. Furthermore, a mouse skin wound infection model infected with C. albicans was established. Wound healing rates and histological examinations were determined 0, 3, 7, 10 and 14 days post‑wounding. The results revealed that C. albicans was eradicated by BL in a dose‑dependent manner, with a minimum fluence of 60 J/cm2. Irradiation with BL almost completely eradicated C. albicans when the light fluence was 240 J/cm2. C. albicans inside biofilms was also eradicated and biofilms were destroyed following BL irradiation at 240 J/cm2. In addition, BL was revealed to significantly suppress C. albicans infection in vivo. Irradiation with BL promoted the wound healing of C. albicans infected‑skin wounds in a mouse model. In conclusion, the results of the present study demonstrated that 460 nm BL may eradicate planktonic and biofilm C. albicans in vitro, and represents a novel therapeutic strategy for the treatment of C. albicans infections in vivo.
Blue light for infectious diseases: Propionibacterium acnes, Helicobacter pylori, and beyond? [2022]Blue light, particularly in the wavelength range of 405-470 nm, has attracted increasing attention due to its intrinsic antimicrobial effect without the addition of exogenous photosensitizers. In addition, it is commonly accepted that blue light is much less detrimental to mammalian cells than ultraviolet irradiation, which is another light-based antimicrobial approach being investigated. In this review, we discussed the blue light sensing systems in microbial cells, antimicrobial efficacy of blue light, the mechanism of antimicrobial effect of blue light, the effects of blue light on mammalian cells, and the effects of blue light on wound healing. It has been reported that blue light can regulate multi-cellular behavior involving cell-to-cell communication via blue light receptors in bacteria, and inhibit biofilm formation and subsequently potentiate light inactivation. At higher radiant exposures, blue light exhibits a broad-spectrum antimicrobial effect against both Gram-positive and Gram-negative bacteria. Blue light therapy is a clinically accepted approach for Propionibacterium acnes infections. Clinical trials have also been conducted to investigate the use of blue light for Helicobacter pylori stomach infections and have shown promising results. Studies on blue light inactivation of important wound pathogenic bacteria, including Staphylococcus aureus and Pseudomonas aeruginosa have also been reported. The mechanism of blue light inactivation of P. acnes, H. pylori, and some oral bacteria is proved to be the photo-excitation of intracellular porphyrins and the subsequent production of cytotoxic reactive oxygen species. Although it may be the case that the mechanism of blue light inactivation of wound pathogens (e.g., S. aureus, P. aeruginosa) is the same as that of P. acnes, this hypothesis has not been rigorously tested. Limited and discordant results have been reported regarding the effects of blue light on mammalian cells and wound healing. Under certain wavelengths and radiant exposures, blue light may cause cell dysfunction by the photo-excitation of blue light sensitizing chromophores, including flavins and cytochromes, within mitochondria or/and peroxisomes. Further studies should be performed to optimize the optical parameters (e.g., wavelength, radiant exposure) to ensure effective and safe blue light therapies for infectious disease. In addition, studies are also needed to verify the lack of development of microbial resistance to blue light.
The Parameters Affecting Antimicrobial Efficiency of Antimicrobial Blue Light Therapy: A Review and Prospect. [2023]Antimicrobial blue light (aBL) therapy is a novel non-antibiotic antimicrobial approach which works by generating reactive oxygen species. It has shown excellent antimicrobial ability to various microbial pathogens in many studies. However, due to the variability of aBL parameters (e.g., wavelength, dose), there are differences in the antimicrobial effect across different studies, which makes it difficult to form treatment plans for clinical and industrial application. In this review, we summarize research on aBL from the last six years to provide suggestions for clinical and industrial settings. Furthermore, we discuss the damage mechanism and protection mechanism of aBL therapy, and provide a prospect about valuable research fields related to aBL therapy.
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. [2021]Objective: To determine effective treatment strategies against bacterial infections of chronic wounds, we tested different blue light (BL)-emitting light-emitting diode arrays (420, 455, and 480 nm) against wound pathogens and investigated in parallel BL-induced toxic effects on human dermal fibroblasts. Background: Wound infection is a major factor for delayed healing. Infections with Pseudomonas aeruginosa and Staphylococcus aureus are clinically relevant caused by their ability of biofilm formation and their quickly growing antibiotics resistance. BL has demonstrated antimicrobial properties against various microbes. Methods: Determination of antibacterial and cell toxic effects by colony-forming units (CFUs)/biofilm/cell viability assays, and live cell imaging. Results: A single BL irradiation (180 J/cm2), of P. aeruginosa at both 420 and 455 nm resulted in a bacterial reduction (>5 log10 CFU), whereas 480 nm revealed subantimicrobial effects (2 log10). All tested wavelengths of BL also revealed bacteria reducing effects on Staphylococcus epidermidis and Escherichia coli (maximum 1-2 log10 CFU) but not on S. aureus. Dealing with biofilms, all wavelengths using 180 J/cm2 were able to reduce significantly the number of P. aeruginosa, E. coli, and S. epidermidis. Here, BL420nm achieved reductions up to 99%, whereas BL455nm and BL480nm were less effective (60-83%). Biofilm-growing S. aureus was more BL sensitive than in the planktonic phase showing a reduction by 63-75%. A significant number of cell toxic events (>40%) could be found after applying doses (>30 J/cm2) of BL420nm. BL455nm showed only slight cell toxicity (180 J/cm2), whereas BL480nm was nontoxic at any dose. Conclusions: BL treatment can be effective against bacterial infections of chronic wounds. Nevertheless, using longer wavelengths >455 nm should be preferred to avoid possible toxic effects on skin and skin cells. To establish BL therapy for infected chronic wounds, further studies concerning biofilm formation and tissue compatibility are necessary.
Clinical and histological effects of blue light on normal skin. [2010]Phototherapy with visible light is gaining interest in dermatological practice. Theoretically, blue light could induce biological effects comparable to ultraviolet A (UVA) radiation.
Characterization of blue light irradiation effects on pathogenic and nonpathogenic Escherichia coli. [2021]Blue light irradiation (BLI) is an FDA-approved method for treating certain types of infections, like acne, and is becoming increasingly attractive as an antimicrobial strategy as the prevalence of antibiotic-resistant "superbugs" rises. However, no study has delineated the effectiveness of BLI throughout different bacterial growth phases, especially in more BLI-tolerant organisms such as Escherichia coli. While the vast majority of E. coli strains are nonpathogenic, several E. coli pathotypes exist that cause infection within and outside the gastrointestinal tract. Here, we compared the response of E. coli strains from five phylogenetic groups to BLI with a 455 nm wavelength (BLI455 ), using colony-forming unit and ATP measurement assays. Our results revealed that BLI455 is not bactericidal, but can retard E. coli growth in a manner that is dependent on culture age and strain background. This observation is critical, given that bacteria on and within mammalian hosts are found in different phases of growth.