The Impact of Circadian Misalignment on Colonic Barrier Homeostasis in Ulcerative Colitis
Study Details
Study Description
Brief Summary
The purpose of this study is to investigate if circadian malalignment (unusual sleeping patterns), such as night shifts (sleeping during the day and being awake during the night time), worsens the inflammation of the gut. We hope to look at patients with Ulcerative Colitis and Healthy Controls.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Sleep Lab
|
Behavioral: 7-day sleep lab
Patients will stay in 7-day sleep lab where light exposure, diet, and activity will be closely monitored. They will have two unprepped flexible sigmoidoscopies with rectal biopsy collection and stool collection. Cycles will be shifted by 12h once on Day 3 of sleep lab and be discharged after an 8 hour sleep session on Day 7.
|
Outcome Measures
Primary Outcome Measures
- Change in the Phase Angle of Entrainment from Baseline (Aligned Circadian Rhythms) to Circadian Misalignment [Blood drawn hourly for eight hours at baseline circadian rhythm (eight draws) and blood drawn hourly for twelve hours at circadian misalignment (12 draws).]
Phase angle of entrainment is the amount of time between dim light melatonin onset to sleep onset. Melatonin concentration in blood serum is measured by ELISA (enzyme-linked immunosorbent assay).
- Change in Intestinal Permeability from Baseline (Aligned Circadian Rhythms) to Circadian Misalignment [24 hour urine collection beginning at baseline and 24 hour urine collection at circadian misalignment.]
Intestinal permeability is assessed through spectrophotometric measurements of sucralose, sucrose, maltose and lactulose concentrations in urine following ingestion of a sugar cocktail.
Secondary Outcome Measures
- Change in 24 hour Urinary Melatonin Concentrations from Baseline (Aligned Circadian Rhythms) to Circadian Misalignment [24 hour urine collection at baseline and 24 hour urine collection at circadian misalignment circadian]
Spectrophotometry
- Change in Mayo Score from Baseline (Aligned Circadian Rhythms) to Circadian Misalignment [30 minute flexible sigmoidoscopy at Baseline and 30 minute flexible sigmoidoscopy at Circadian Misalignment]
Within the endoscopic component of the Mayo Score, a score of 0 is given for normal mucosa or inactive UC, while a score of 1 is given for mild disease with evidence of mild friability, reduced vascular pattern, and mucosal erythema.
- Change in Stool Calprotectin from Baseline (Aligned Circadian Rhythms) to Circadian Misalignment [10 minute stool collection conducted at baseline circadian rhythm and at circadian misalignment.]
Calprotectin is a sensitive marker for inflammation in the gastrointestinal tract. Measured through enzyme linked immunosorbent assay for calprotectin in stool extract.
- Change in Concentration of Serum Cytokine Markers of Inflammation from Baseline (Aligned Circadian Rhythms) to Circadian Misalignment [Blood is drawn every two hours over a 24 hour period at baseline (12 draws), and blood is drawn every two hours over a 24 hour period at circadian misalignment]
Enzyme linked immunosorbent assay
- Changes in Clock Gene Expression in Peripheral Blood Mononuclear Cells from Baseline (Aligned Circadian Rhythms) to Circadian Misalignment [Blood is drawn every two hours over a 24 hour period at baseline (12 draws), and blood is drawn every two hours over a 24 hour period at circadian misalignment]
RNA Sequencing
- Changes in Gene Expression of Colonic Tissue Biopsies from Baseline (Aligned Circadian Rhythms) to Circadian Misalignment [30 minute flexible sigmoidoscopy at Baseline and 30 minute flexible sigmoidoscopy at Circadian Misalignment]
Tissue biopsies collected during flexible sigmoidoscopy conducted at Baseline Circadian Rhythm and at Circadian Misalignment. Assessed through histology and RNA Sequencing
Other Outcome Measures
- Diet [Once before sleep lab]
Vioscreen Food Frequency Questionnaire (FFQ). Total of 19 measured food components. Vioscreen captures comprehensive dietary behaviors in just 30 minutes. It is a unique dietary questionnaire, management and analysis system that efficiently gathers and manages data that immediately identifies dietary "habits" and counsel for lifestyle changes.
- Single day food recall [Once before sleep lab]
Automated Self-Administered 24-Hour Recall (ASA24) Dietary Assessment. Total nutrients from all supplements reported in a given day.
- Chronotype [Screening]
The Munich ChronoType Questionnaire (MCTQ) uses a self-rated scale to assess individual phase of entrainment on work and work-free days; it is a tool to collect primary sleep times, such as bed- and rise-times, plus the clock time of becoming fully awake as well as sleep latency and inertia, in addition to other time points.
- Inflammatory Bowel Disease Questionnaire [Screening]
32-item Inflammatory Bowel Disease Questionnaire (IBDQ-32) is the most frequently used instrument to capture disease-specific quality of life in randomized clinical trials for ulcerative colitis
- Beck Depression Inventory [3 Weeks prior to circadian lab assessments]
The Beck Depression Inventory (BDI, BDI-II), created by Dr. Aaron T. Beck, is a 21-question multiple-choice self-report inventory, one of the most widely used instruments for measuring the severity of depression.
- The State-Trait Anxiety Inventory [Screening]
The State-Trait Anxiety Inventory (STAI) is a commonly used measure of trait and state anxiety
- Perceived Stress Questionnaire [Screening]
Consisting of 30 items, the Perceived Stress Questionnaire was developed as an instrument for assessing the stressful life events and circumstances that tend to trigger or exacerbate disease symptoms.
- The International Restless Legs Syndrome Study Group Rating Scale [Screening]
Subjective scale to measure disease severity of restless legs syndrome in the past week
- Berlin Questionnaire [Screening]
The questionnaire consists of 3 categories related to the risk of having sleep apnea
- Pittsburgh Sleep Quality Index [3 Weeks prior to circadian lab assessments]
The following questions relate to your usual sleep habits during the past month only.
Eligibility Criteria
Criteria
Inclusion Criteria:
UC patients:
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Inactive Disease (Mayo Score ≤ 2)
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Stable medications with no disease flares for the > 3 months
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Left-sided UC (Montreal E1 or E2)
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Normal psychological evaluation and negative drug screen (See Below)
Healthy Controls:
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M/F, 18-40 y/o, age ± 3y sex, race, and BMI match with UC subject
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No clinical evidence of any medical illness
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Normal psychological evaluation and negative drug screen (See Below)
Exclusion Criteria:
UC patients:
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Patients with other forms of colitis such as Crohn's disease (CD) or indeterminate colitis
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Patient with active UC (Mayo > 2)
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Pancolonic UC (colitis past the splenic flexure, Montreal E3))
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Use of biologic or immunomodulatory medications (i.e. Infliximab, Adalimumab, azathioprine, Vedolizumab, methotrexate, etc.)
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Gastrointestinal surgery
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Other GI diseases or systemic diseases (cardiac, renal failure, cirrhosis)
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Shift work in the last 6 months
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Antibiotic use within last 12 weeks
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Patients who have used anti-diarrheal agents such as Lomotil or Imodium within 3 days of the study
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Prednisone use the last 30 days
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Significant Depression (score ≥ 14 BDI)
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Significant Anxiety (score ≥ 40 STAI)
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Use of probiotic supplement in last 4 weeks except yogurt.
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Intentional change in diet.
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Chronic use of NSAIDS. A washout period of 3 weeks is needed before the subject could be enrolled into the study. Low dose aspirin is allowed.
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Chronic Alcohol use. A washout period of 3 weeks is needed before the subject could be enrolled into the study.
Healthy Controls:
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History of drug abuse, gastrointestinal (GI) surgery, GI diseases, or systemic diseases such as renal (creatinine>1.2 mg/dl), liver, cardiac, or diabetes (Hgb-A1c>8%)
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Antibiotic use within last 12 weeks
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Shift work in the last 6 months
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Use of probiotic supplement except yogurt in last 4 weeks.
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Atypical American diet with daily fiber ≥ 16 grams or daily saturated fat ≤ 11 grams by Food Frequency Questionnaire
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Chronic use of NSAIDS. A washout period of 3 weeks is needed before the subject could be enrolled into the study.
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Chronic Alcohol use. A washout period of 3 weeks is needed before the subject could be enrolled into the study.
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Significant Depression (score ≥ 14 BDI)
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Significant Anxiety (score ≥ 40 STAI)
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Regular use of medications that affect intestinal permeability, intestinal motility and/or endogenous melatonin including metoclopramide, NSAIDs, antibiotics, beta blocker, psychotropic medication, hypnotics and exogenous melatonin products during 4 weeks prior to the study
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People who crossed more than 2 time zones in the previous month
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Inability to sign an informed consent form.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Rush University Medical Center | Chicago | Illinois | United States | 60612 |
Sponsors and Collaborators
- Rush University Medical Center
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
None specified.Study Documents (Full-Text)
More Information
Publications
None provided.- 19051402