The Role of Circadian Clock Proteins in Innate and Adaptive Immunity

NCT03482245 | Recruiting DMC

• 2 other identifiers: STUDY190303761R01GM145674
• Study Type: interventional
• Target: 144
• Locations: 1 country
• Sites: 1

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. 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.

Conditions

Necrotizing Soft Tissue Infection; Intraabdominal Infections; Pneumonia; Infection Joint

Keywords

pneumonia; soft tissue infection; intraabdominal infections; circadian rhythms; blue light; sepsis

Outcome Measures

Primary Outcomes (3)

• Pneumonia: change in bronchoalveolar lavage (BAL) bacteria concentration

  quantification of the change in bacterial colony forming units (CFU) in BAL fluid

  comparing time of randomization and at 72 hours after randomization

• All groups: change in expression of circadian proteins in circulating immune cells

  quantification of the change in blood white blood cell counts

  comparing time of randomization and at 72 hours after randomization

• All Cohorts: change in serum concentrations of circulating inflammatory mediators in the blood

  quantification of change in serum cytokine concentrations

  comparing time of randomization and at 72 hours after randomization

Secondary Outcomes (3)

• Pneumonia: need for and duration of mechanical ventilation

  comparing time of randomization to 28 days

• All Cohorts: change in organ dysfunction

  comparing time of randomization and at 72 hours after randomization

• Appendicitis and Diverticulitis: intraabdominal abscess formation

  from time of randomization to 28-days after randomization

Study Arms (8)

Pneumonia: Blue Light

EXPERIMENTAL

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.

Other: Blue Light

Intraabdominal infection: Blue Light

EXPERIMENTAL

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.

Other: Blue Light

Necrotizing Soft Tissue Infection: Blue Light

EXPERIMENTAL

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.

Other: Blue Light

Pneumonia: Ambient Light

NO 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.

Intraabdominal infection: Ambient Light

NO 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.

Necrotizing Soft Tissue Infection: Ambient Light

NO 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.

Infected Joint: Blue Light

EXPERIMENTAL

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.

Other: Blue Light

Infected Joint: Ambient Light

NO 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.

Interventions

Blue Light OTHER

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 442 nm) such that it produces 1700 Lux of blue spectrum lighting when positioned at a distance of 12 inches from the subject. 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.

Infected Joint: Blue Light; Intraabdominal infection: Blue Light; Necrotizing Soft Tissue Infection: Blue Light; Pneumonia: Blue Light

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• greater than or equal to 18 years of age and less than or equal to 65 years of age
• one of the following diagnoses requiring inpatient hospital care
• an operation for intraabdominal infection
• an operation for necrotizing soft tissue infection
• an operation for an infected joint
• medical treatment of pneumonia.

You may not qualify if:

• traumatic brain injury
• blindness
• immunocompromised or immunosuppressed state
• infection requiring treatment in preceding 30 days
• blindness
• SARS-CoV-2

Sponsors & Collaborators

• National Institute of General Medical Sciences (NIGMS): collaborator
• Washington University School of Medicine: lead

Study Sites (1)

Barnes Jewish Hospital

St Louis, Missouri, 63108, United States

RECRUITING

MeSH Terms

Conditions

Pneumonia; Intraabdominal Infections; Soft Tissue Infections; Sepsis

Interventions

Blue Light

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Light; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena; Optical Phenomena; Radiation; Radiation, Nonionizing

Study Officials

• Matthew R Rosengart, MD MPH

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Matthew R Rosengart, MD MPH

CONTACT

314-362-5298; matthew.r@wustl.edu

Xianghong Zhang, PhD

CONTACT

412-215-6134; xianghong@wustl.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: randomized pilot clinical trial

Study Record Dates

• First Submitted: March 20, 2018
• First Posted: March 29, 2018
• Study Start: October 29, 2024
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: February 11, 2026

Record last verified: 2026-02

Locations

US (1)