The Impact of Circadian Misalignment on Colonic Barrier Homeostasis in Ulcerative Colitis

Ulcerative Colitis Clinical Trial

Official title:

The Impact of Circadian Misalignment on Colonic Barrier Homeostasis in Ulcerative Colitis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05180279
• Other study ID #: 19051402
• Status: Recruiting
• Phase: N/A
• Start date: April 1, 2021
• Est. completion date: June 1, 2024

Study information

• Verified date: February 2024
• Source: Rush University Medical Center
• Contact: Daynia Sanchez-Bass
• Phone: (312)563-4981
• Email: daynia_sanchez-bass[@]rush.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: June 1, 2024
• Est. primary completion date: June 1, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

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) Exclusion Criteria:

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

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

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.

Locations

Country	Name	City	State
United States	Rush University Medical Center	Chicago	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Rush University Medical Center	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Diet	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.	Once before sleep lab
Other	Single day food recall	Automated Self-Administered 24-Hour Recall (ASA24) Dietary Assessment. Total nutrients from all supplements reported in a given day.	Once before sleep lab
Other	Chronotype	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.	Screening
Other	Inflammatory Bowel Disease Questionnaire	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	Screening
Other	Beck Depression Inventory	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.	3 Weeks prior to circadian lab assessments
Other	The State-Trait Anxiety Inventory	The State-Trait Anxiety Inventory (STAI) is a commonly used measure of trait and state anxiety	Screening
Other	Perceived Stress Questionnaire	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.	Screening
Other	The International Restless Legs Syndrome Study Group Rating Scale	Subjective scale to measure disease severity of restless legs syndrome in the past week	Screening
Other	Berlin Questionnaire	The questionnaire consists of 3 categories related to the risk of having sleep apnea	Screening
Other	Pittsburgh Sleep Quality Index	The following questions relate to your usual sleep habits during the past month only.	3 Weeks prior to circadian lab assessments
Primary	Change in the Phase Angle of Entrainment from Baseline (Aligned Circadian Rhythms) to Circadian Misalignment	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).	Blood drawn hourly for eight hours at baseline circadian rhythm (eight draws) and blood drawn hourly for twelve hours at circadian misalignment (12 draws).
Primary	Change in Intestinal Permeability from Baseline (Aligned Circadian Rhythms) to Circadian Misalignment	Intestinal permeability is assessed through spectrophotometric measurements of sucralose, sucrose, maltose and lactulose concentrations in urine following ingestion of a sugar cocktail.	24 hour urine collection beginning at baseline and 24 hour urine collection at circadian misalignment.
Secondary	Change in 24 hour Urinary Melatonin Concentrations from Baseline (Aligned Circadian Rhythms) to Circadian Misalignment	Spectrophotometry	24 hour urine collection at baseline and 24 hour urine collection at circadian misalignment circadian
Secondary	Change in Mayo Score from Baseline (Aligned Circadian Rhythms) to 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.	30 minute flexible sigmoidoscopy at Baseline and 30 minute flexible sigmoidoscopy at Circadian Misalignment
Secondary	Change in Stool Calprotectin from Baseline (Aligned Circadian Rhythms) to Circadian Misalignment	Calprotectin is a sensitive marker for inflammation in the gastrointestinal tract. Measured through enzyme linked immunosorbent assay for calprotectin in stool extract.	10 minute stool collection conducted at baseline circadian rhythm and at circadian misalignment.
Secondary	Change in Concentration of Serum Cytokine Markers of Inflammation from Baseline (Aligned Circadian Rhythms) to Circadian Misalignment	Enzyme linked immunosorbent assay	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
Secondary	Changes in Clock Gene Expression in Peripheral Blood Mononuclear Cells from Baseline (Aligned Circadian Rhythms) to Circadian Misalignment	RNA Sequencing	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
Secondary	Changes in Gene Expression of Colonic Tissue Biopsies from Baseline (Aligned Circadian Rhythms) to Circadian Misalignment	Tissue biopsies collected during flexible sigmoidoscopy conducted at Baseline Circadian Rhythm and at Circadian Misalignment. Assessed through histology and RNA Sequencing	30 minute flexible sigmoidoscopy at Baseline and 30 minute flexible sigmoidoscopy at Circadian Misalignment