The Impact of Circadian Misalignment on Colonic Barrier Homeostasis in Ulcerative Colitis
- Conditions
- Ulcerative Colitis
- Interventions
- Behavioral: 7-day sleep lab
- Registration Number
- NCT05180279
- Lead Sponsor
- Rush University Medical Center
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 19
UC patients:
- M/F, 18-50 y/o
- Inactive Disease (Mayo Score ≤ 2)
- Stable medications with no disease flares for the > 3 months
- Left-sided UC (Montreal E1 or E2)
- Normal psychological evaluation and negative drug screen (See Below)
Healthy Controls:
- M/F, 18-50 y/o, age ± 3y sex, race, and BMI match with UC subject
- No clinical evidence of any medical illness
- Normal psychological evaluation and negative drug screen (See Below)
UC patients:
- Patients with other forms of colitis such as Crohn's disease (CD) or indeterminate colitis
- Patient with active UC (Mayo > 2)
- Pancolonic UC (colitis past the splenic flexure, Montreal E3))
- Use of biologic or immunomodulatory medications (i.e. Infliximab, Adalimumab, azathioprine, Vedolizumab, methotrexate, etc.)
- Gastrointestinal surgery
- Other GI diseases or systemic diseases (cardiac, renal failure, cirrhosis)
- Shift work in the last 6 months
- Antibiotic use within last 12 weeks
- Patients who have used anti-diarrheal agents such as Lomotil or Imodium within 3 days of the study
- Prednisone use the last 30 days
- Significant Depression (score ≥ 14 BDI)
- Significant Anxiety (score ≥ 40 STAI)
- Use of probiotic supplement in last 4 weeks except yogurt.
- Intentional change in diet.
- 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.
- Chronic Alcohol use. A washout period of 3 weeks is needed before the subject could be enrolled into the study.
- Have children under 6 months
Healthy Controls:
- 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%)
- Antibiotic use within last 12 weeks
- Shift work in the last 6 months
- Use of probiotic supplement except yogurt in last 4 weeks.
- Atypical American diet with daily fiber ≥ 16 grams or daily saturated fat ≤ 11 grams by Food Frequency Questionnaire
- Chronic use of NSAIDS. A washout period of 3 weeks is needed before the subject could be enrolled into the study.
- Chronic Alcohol use. A washout period of 3 weeks is needed before the subject could be enrolled into the study.
- Significant Depression (score ≥ 14 BDI)
- Significant Anxiety (score ≥ 40 STAI)
- 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
- People who crossed more than 2 time zones in the previous month
- Inability to sign an informed consent form.
- Have children under 6 months
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Sleep Lab 7-day sleep lab -
- Primary Outcome Measures
Name Time Method 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.
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).
- Secondary Outcome Measures
Name Time Method 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
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.
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
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
Trial Locations
- Locations (1)
Rush University Medical Center
🇺🇸Chicago, Illinois, United States