A Randomized Crossover Trial of Bright Light Therapy in Crohn's Disease on Intestinal Barrier Homeostasis

• ClinicalTrials.gov Identifier: NCT05579392
• Recruitment Status: Recruiting
• First Posted: October 13, 2022
• Last Update Posted: February 21, 2023
• Sponsor: Rush University Medical Center
• Information provided by (Responsible Party): Garth Swanson, MD, Rush University Medical Center

Tracking Information

• First Submitted Date: September 22, 2022
• First Posted Date: October 13, 2022
• Last Update Posted Date: February 21, 2023
• Actual Study Start Date: September 22, 2022
• Estimated Primary Completion Date: July 1, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 12, 2022)

• Changes in intestinal permeability (% excretion of urinary sucralose) [ Time Frame: 15 weeks ]
  Participants will ingest a sugar cocktail at Visits 2-5 and complete a urine collection. Measurement of urinary sugars is done using gas chromatography is used to calculate intestinal permeability.
• Changes in microbiota will be assessed using shotgun metagene sequencing and total microbial community DNA [ Time Frame: 15 weeks ]
  At all study visits, stool samples will be collected and analyzed using shotgun metagene sequencing and total microbial community DNA will be isolated and processed for microbiome analysis.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 12, 2022)

• Change in systemic markers of barrier disruption and inflammation [ Time Frame: 15 weeks ]
  Inflammatory cytokines (IL-6, TNF-α, and IL-8) are the markers of disruption. IL-6, IL-8, and TNF-α will be measured in the plasma.
• Change in systemic markers of inflammation [ Time Frame: 15 weeks ]
  markers of endotoxemia (LPS, LBP, and sCD14) will be used to assess inflammation. Lipopolysaccharide binding protein(LBP) and sCD14 will be measured in serum by high sensitivity ELISA. Lipopolysaccharide (LPS) will be measured in serum using a LAL assay which is a quantitative, kinetic assay for the detection of Gram-negative bacterial endotoxin.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Randomized Crossover Trial of Bright Light Therapy in Crohn's Disease on Intestinal Barrier Homeostasis
• Official Title: Bright Light Therapy in Crohn's Disease on Intestinal Barrier Homeostasis
• Brief Summary: Crohn's Disease (CD) and Ulcerative Colitis (UC), collectively known as inflammatory bowel disease (IBD), are two of the most significant chronic conditions of the gastrointestinal tract (GIT). IBD affects over 1.5 million individuals in the US, so identifying risk factors for disease flares is essential to avoid complications, such as hospitalizations and surgery, and to improve quality of life (QoL). Recently, there has been an increased understanding of the importance of sleep and sleep disruption in IBD as a potentially modifiable risk factor.

Detailed Description

Crohn's Disease (CD) and Ulcerative Colitis (UC), collectively known as inflammatory bowel disease (IBD), are two of the most significant chronic conditions of the gastrointestinal tract (GIT). IBD affects over 1.5 million individuals in the US, so identifying risk factors for disease flares is essential to avoid complications, such as hospitalizations and surgery, and to improve quality of life (QoL). Recently, there has been an increased understanding of the importance of sleep and sleep disruption in IBD as a potentially modifiable risk factor.

Bright light therapy (BLT) in IBD patients with CM may decrease intestinal permeability and pro-inflammatory cytokines, positively impact intestinal microbiota, and improve quality of life (QoL).In order to administer BLT efficiently and safely, a Re-Timer device, which is a lightweight, wearable set of glasses that emits blue-green light. Please note, the FDA has determined this device to be a General Wellness product and is not regulated by the FDA.

Prior to starting treatment, IBD patients will be screened for subclinical inflammation using a fecal calprotectin (FC) level and a blood test. If no subclinical inflammation is detected, potential subjects will be informed of their ineligibility. Eligible participants will complete questionnaires assessing their dietary habits, fatigue, sleep habits, QoL, and severity of their underlying disease. Participants will also be provided a wrist actigraphy, which is a watch like device, to wear for 21 days to objectively assess CM prior to initiating therapy. Once the subjects demonstrate both subjective and objective evidence of CM, during their follow-up visit they will be randomly assigned to wear either the Re-Timer device to receive BLT or the placebo Re-Timer device (non BLT) for 4 weeks. Prior to and following receiving BLT or non BLT placebo, the following samples will be obtained: i) serum markers of inflammation and endotoxemia, ii) urine samples to test for intestinal permeability, and iii) stool samples to assess intestinal microbiota. These proposed studies will assess whether BLT has an impact on IBD patients' inflammation, intestinal permeability, and intestinal microbiota.

• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:

Participants will be randomly assigned to receive Bright light therapy or placebo (wearing a similar device but will not receive the therapy) for 4 weeks, then they will do a washout period. After the washout period, the same participants will crossover to the opposite group for the remaining 4 weeks of the study, i.e. placebo or bright light therapy.

Masking: Single (Participant)
Primary Purpose: Basic Science

• Condition: Inflammatory Bowel Disease

Intervention

• Device: Bright Light Therapy
  Device: Bright Light Therapy Retimer
• Device: Placebo Retimer Device
  Device: Placebo Retimer Device with no bright light therapy

Study Arms

• Experimental: Bright Light Therapy via ReTimer glasses, Then Placebo
  Participants will wear their device for 60 minutes every morning for 28-days (4 weeks)
  Interventions:

  • Device: Bright Light Therapy
  • Device: Placebo Retimer Device
• Experimental: No Bright Light Therapy via placebo glasses, Then Bright Light Therapy
  Participants will wear their placebo device for 60 minutes every morning for 28-days (4 weeks)
  Interventions:

  • Device: Bright Light Therapy
  • Device: Placebo Retimer Device

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 12, 2022): 30
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 31, 2025
• Estimated Primary Completion Date: July 1, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Biopsy proven diagnosis of Crohn's or Ulcerative Colitis
• 18 years or older
• Fecal Calprotectin > 50 or CRP > 5 or a FACIT Score ≥ 4
• Has been on a stable dose of either a biologic, immunomodulator, or 5-ASA for at least 12 weeks

Exclusion Criteria:

• Active IBD (Harvey Bradshaw Index < 5 or Modified Harvey Bradshaw Index <5)
• Major depression (score ≥ 15 or any endorsement of suicidal intent on the Beck Depression)
• Sleep apnea (score high risk in 2 or more categories of the Berlin Questionnaire) (43)
• Restless leg syndrome (score ≥ 15 on the IRLS Study Group Rating Scale(44))
• Regular use of medications that affect intestinal permeability, and/or endogenous melatonin including metoclopramide, NSAIDs, beta blockers, psychotropic medications, hypnotics and exogenous melatonin products during 4 weeks prior to the study
• People who have worked night shifts or crossed more than 2 time zones in the previous month
• Any major organ disease - renal impairment (creatinine>1.2 mg/dL), diabetes (Hgb-A1c > 6.5%); liver disease (LFTs > 1.5x normal), or significant cardiac failure (NY classification stage III/IV)
• Diagnosis of narrow angle glaucoma or retinal disorders or demonstrated symptoms indicative of these diagnosis during the eligibility screening
• Inability to sign an informed consent

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Netanel Zilberstein; 818-439-7871; Netanel_F_Zilberstein@rush.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05579392
• Other Study ID Numbers: 22041302
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Garth Swanson, MD, Rush University Medical Center
• Original Responsible Party: Same as current
• Current Study Sponsor: Rush University Medical Center
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Netanel Zilberstein; Rush University Medical Center

• PRS Account: Rush University Medical Center
• Verification Date: February 2023