Blue Light Therapy in Reducing Inflammation During Sepsis

• ClinicalTrials.gov Identifier: NCT03482245
• Recruitment Status: Recruiting
• First Posted: March 29, 2018
• Last Update Posted: March 2, 2022
• Sponsor: University of Pittsburgh
• Information provided by (Responsible Party): Matthew Rosengart, University of Pittsburgh

Study Description

Brief Summary:

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.

This study is an experimental investigation of exposure to blue (480nm) light in the setting of appendectomy for appendicitis, colon resection for diverticulitis, or treatment of pneumonia

The exposure of interest is blue light applied prior to surgery and during the 24 hour period after surgery.

For the cohort with pneumonia, exposure of interest is blue light applied upon diagnosis of pneumonia for a 24 hour period after diagnosis and then for a 12 hour period on days 2 and 3 of treatment of pneumonia.

The control group is comprised of controls that have undergone a similar operation or treatment for pneumonia but without exposure to blue light.

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.

Condition or disease	Intervention/treatment	Phase
Pneumonia; Appendicitis; Diverticulitis	Other: Blue Light	Not Applicable

Detailed Description:

Background and preliminary data:

Our murine studies suggest that exposure to blue (480nm) light, by comparison to ambient white or amber (580nm) light, reduces the inflammatory response (i.e., cytokine concentration), risk of organ failure (i.e., kidney failure), and improves the clearance and control of the infectious focus (i.e., reduced abdominal and pulmonary bacterial counts and bacterial dissemination into tissues of the liver and spleen) in mice subjected to a model of cecal ligation and puncture (CLP) or a model of pneumonia. These data directly support the proposed project and experimentation.

Exposure to blue light after a cecal ligation and puncture (CLP) model of sepsis reduces systemic inflammation, as evidenced by reduced serum TNF-alpha, IL-6 and IL-10 concentrations. These mice had reduced bacterial in the abdomen and reduced bacteremia. They also had reduced kidney failure after sepsis by comparison to mice subjected to ambient light. Similar data were observed in mice subjected to a model of Klebsiella pneumoniae: improved survival, reduced bacteria within the lung, reduced bacteremia and dissemination into the tissues of the liver and spleen, and reduced systemic inflammation in mice exposed to blue light.

Significance:

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. Importantly, the risk of light is minimal. Thus, the intervention of exposing a patient to a characteristic spectrum of light carries a very large benefit:risk ratio. The results of these studies may be directly applicable to a more generalized population of critically ill patients.

Approach:

Subjects will receive the standard preoperative, intraoperative, and postoperative care for appendectomy or colon resection. All operations will be performed by one of the Trauma/Acute Care Surgery surgeons at PUH. Subjects with pneumonia will receive standard medical care for pneumonia. All medical care will be performed by one of the Critical Care Physicians at PUH. There are no deviations from the standard care received for subjects with these diagnoses.

Discussions of the study, informed consent, and subsequent subject interaction will occur during the initial visit that occurs in the hospital at the time of diagnosis.

There are 4 groups that are being evaluation:

1. subjects undergoing appendectomy and exposed to Blue light: n=12
2. subjects undergoing appendectomy and NOT exposed to Blue light: n=12
3. subjects undergoing colon resection for diverticulitis and exposed to Blue light: n=12
4. subjects undergoing colon resection for diverticulitis and NOT exposed to Blue light: n=12
5. subjects with pneumonia and exposed to Blue light: n=12
6. subjects with pneumonia and NOT exposed to Blue light: n=12

Subjects that are to be exposed to Blue light will be provided by the research personnel (Dr. Rosengart) with a Day-Light Classic 10,000 lumen SAD light, a device that has been used in many of the previously listed published studies (Epilepsy Behav. 2012 Jul;24(3):359-64. doi: 10.1016/j.yebeh.2012.04.123. Epub 2012 May 30.) This light is fitted with a blue spectrum filter, such that it produces 2000 lumens of blue spectrum lighting at a distance of 12 inches. This intensity of light is 1/5 of what has been used in prior human studies. The comparative groups that are not exposed to Blue light do not receive this light, but otherwise, undergo identical standard of care and will have blood drawn for research purposes.

At the time of enrollment subjects to be exposed to Blue light will be instructed in the use of the light, though during the period of light exposure the light will be managed by the investigative team. The light is small (4 X 16 X 21 inches) and weights less than a pound. It is UV filtered and glare free. There is a single "On/Off" switch.

This study is one of effectiveness rather than efficacy. Thus, there are no rigid guidelines that are mandated regarding location or duration of lighting or other environmental restrictions.

Surgical cohort: On the day of surgery, subjects that are to be exposed to Blue light will be exposed to the blue spectrum light after consent and prior to the operation. They will also be exposed to the light for a 24 hour period postoperatively. This light exposure will be initiated, maintained, and removed by Dr. Matthew Rosengart. The light will be positioned 12 inches from the subject for the period prior to and for 24 hours during postoperative day 1. At any time the subject may request the light to be removed.

Preoperative and postoperative standard care, including blood sample analysis will be directed by the surgical team and performed at UPMC PUH hospital.

Pneumonia cohort: On the day of diagnosis of pneumonia, subjects that are to be exposed to Blue light will be exposed to the blue spectrum light after consent. They will be exposed to the light for a 24 hour period after diagnosis. They will also be exposed to the blue light for 12 hours on days 2 and 3 of treatment of pneumonia. The light exposure will be initiated, maintained, and removed by Dr. Matthew Rosengart. The light will be positioned 12 inches from the subject for the period prior to and for 24 hours during postoperative day 1. At any time the subject may request the light to be removed.

For ALL subjects we will abstract data from the electronic record regarding white blood cell count.

An additional 2 samples of blood will be obtained for research purposes only to measure serum cytokine concentrations. These blood samples are obtain from ALL subjects in the study.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 72 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: randomized pilot clinical trial
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Light Therapy in Patients Undergoing Appendectomy for Appendicitis, Colon Resection for Diverticulitis, or Treatment of Pneumonia
• Actual Study Start Date: March 1, 2018
• Estimated Primary Completion Date: July 31, 2025
• Estimated Study Completion Date: December 31, 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Pneumonia: Blue Light; High illuminance (1000lux), blue spectrum (peak 441 nm) light for an initial 24 hour photoperiod and then a 12 hour photoperiod for days 2 and 3 after randomization.	Other: Blue Light; Subjects that are to be exposed to blue light will be provided by the research personnel with a Day-Light Classic 10,000 lumen SAD light, a device that has been used in many of the previously listed published studies (Epilepsy Behav. 2012 Jul;24(3):359-64. doi: 10.1016/j.yebeh.2012.04.123. Epub 2012 May 30.) The light is small (4 X 16 X 21 inches) and weights less than a pound. It is UV filtered and glare free. There is a single "On/Off" switch. It will be attached to a rolling stand. This light is fitted with a blue spectrum filter (peak 441 nm) such that it produces 1000 Lux of blue spectrum lighting when positioned at a distance of 12 inches from the subject.
Experimental: Diverticulitis: Blue Light; High illuminance (1000lux), blue spectrum (peak 441 nm) light for an initial 24 hour photoperiod after surgery for diverticulitis	Other: Blue Light; Subjects that are to be exposed to blue light will be provided by the research personnel with a Day-Light Classic 10,000 lumen SAD light, a device that has been used in many of the previously listed published studies (Epilepsy Behav. 2012 Jul;24(3):359-64. doi: 10.1016/j.yebeh.2012.04.123. Epub 2012 May 30.) The light is small (4 X 16 X 21 inches) and weights less than a pound. It is UV filtered and glare free. There is a single "On/Off" switch. It will be attached to a rolling stand. This light is fitted with a blue spectrum filter (peak 441 nm) such that it produces 1000 Lux of blue spectrum lighting when positioned at a distance of 12 inches from the subject.
Experimental: Appendicitis: Blue Light; High illuminance (1000lux), blue spectrum (peak 441 nm) light for an initial 24 hour photoperiod after surgery for diverticulitis	Other: Blue Light; Subjects that are to be exposed to blue light will be provided by the research personnel with a Day-Light Classic 10,000 lumen SAD light, a device that has been used in many of the previously listed published studies (Epilepsy Behav. 2012 Jul;24(3):359-64. doi: 10.1016/j.yebeh.2012.04.123. Epub 2012 May 30.) The light is small (4 X 16 X 21 inches) and weights less than a pound. It is UV filtered and glare free. There is a single "On/Off" switch. It will be attached to a rolling stand. This light is fitted with a blue spectrum filter (peak 441 nm) such that it produces 1000 Lux of blue spectrum lighting when positioned at a distance of 12 inches from the subject.
No Intervention: Pneumonia: Ambient Light; Standard ambient hospital lighting (~300 lux) for an initial 24 hour photoperiod and then a 12 hour photoperiod for days 2 and 3 after randomization.
No Intervention: Diverticulitis: Ambient Light; Standard ambient hospital lighting (~300 lux)for an initial 24 hour photoperiod after surgery for diverticulitis.
No Intervention: Appendicitis: Ambient Light; Standard ambient hospital lighting (~300 lux) for an initial 24 hour photoperiod after surgery for diverticulitis.

Outcome Measures

Primary Outcome Measures :

1. Pneumonia: change in bronchoalveolar lavage (BAL) bacteria concentration [ Time Frame: comparing time of randomization and at 72 hours after randomization ]
   quantification of the change in bacterial colony forming units (CFU) in BAL fluid
2. Appendicitis and Diverticulitis: change in systemic inflammation [ Time Frame: comparing time of randomization and at 72 hours after randomization ]
   quantification of the change in blood white blood cell counts

Secondary Outcome Measures :

1. Pneumonia: change in bronchoalveolar lavage (BAL) neutrophil concentration [ Time Frame: comparing time of randomization and at 72 hours after randomization ]
   quantification of change in neutrophil counts in BAL fluid
2. All Cohorts: change in serum cytokine concentrations [ Time Frame: comparing time of randomization and at 72 hours after randomization ]
   quantification of change in serum cytokine concentrations
3. Appendicitis and Diverticulitis: intraabdominal abscess formation [ Time Frame: from time of randomization to 28-days after randomization ]
   assessment of development of intraabdominal abscess

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• All patients greater than or equal to 18 years old and undergoing 1) appendectomy for appendicitis, 2) colon resection for diverticulitis,, and 3) treatment of pneumonia.

Exclusion Criteria:

• traumatic brain injury, blindness, immunocompromised or immunosuppressed state

Contacts and Locations

Contacts

Contact: Matthew R Rosengart, MD MPH; 412-647-0597; mrr18@pitt.edu

Contact: John E Griepentrog, MD; 412-298-2294; griepentrogje@upmc.edu

Locations

United States, Pennsylvania

UPMC-Presbyterian Hospital; Recruiting

Pittsburgh, Pennsylvania, United States, 15213

Contact: Matthew R Rosengart, MD MPH 412-983-7648 mrr18@pitt.edu

Contact: John E Griepentrog 4122982294 griepentrogje@upmc.edu

Sponsors and Collaborators

University of Pittsburgh

Investigators

• Principal Investigator: Matthew R Rosengart, MD MPH; University of Pittsburgh

More Information

• Responsible Party: Matthew Rosengart, Professor, University of Pittsburgh
• ClinicalTrials.gov Identifier: NCT03482245
• Other Study ID Numbers: PRO14070146
• First Posted: March 29, 2018
• Last Update Posted: March 2, 2022
• Last Verified: March 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Matthew Rosengart, University of Pittsburgh:

pneumonia; appendicitis; diverticulitis; circadian rhythms; blue light; sepsis

Additional relevant MeSH terms:

Pneumonia; Appendicitis; Diverticulitis; Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases; Intraabdominal Infections; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Cecal Diseases; Intestinal Diseases; Diverticular Diseases