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

Primary Purpose

Ulcerative Colitis

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
7-day sleep lab
Sponsored by
Rush University Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Ulcerative Colitis focused on measuring Circadian Rhythms

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Rush University Medical CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Sleep Lab

Arm Description

Outcomes

Primary Outcome Measures

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).
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.

Secondary Outcome Measures

Change in 24 hour Urinary Melatonin Concentrations from Baseline (Aligned Circadian Rhythms) to Circadian Misalignment
Spectrophotometry
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.
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.
Change in Concentration of Serum Cytokine Markers of Inflammation from Baseline (Aligned Circadian Rhythms) to Circadian Misalignment
Enzyme linked immunosorbent assay
Changes in Clock Gene Expression in Peripheral Blood Mononuclear Cells from Baseline (Aligned Circadian Rhythms) to Circadian Misalignment
RNA Sequencing
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

Full Information

First Posted
December 14, 2021
Last Updated
October 13, 2023
Sponsor
Rush University Medical Center
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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1. Study Identification

Unique Protocol Identification Number
NCT05180279
Brief Title
The Impact of Circadian Misalignment on Colonic Barrier Homeostasis in Ulcerative Colitis
Official Title
The Impact of Circadian Misalignment on Colonic Barrier Homeostasis in Ulcerative Colitis
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 1, 2021 (Actual)
Primary Completion Date
February 1, 2024 (Anticipated)
Study Completion Date
June 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Rush University Medical Center
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ulcerative Colitis
Keywords
Circadian Rhythms

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
40 human subjects will be recruited into this proposed study: 20 Healthy Controls and 20 UC subjects with left sided inactive disease. Patients will be matched with Health Controls. Patients will have two study visits: the first is the initial in-clinic screening and the second is the 7-day sleep lab intervention. There will be no follow-up after the lab.
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Daynia Sanchez-Bass
Phone
(312)563-4981
Email
daynia_sanchez-bass@rush.edu
Facility Information:
Facility Name
Rush University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Daynia M. Sanchez-Bass
Phone
312-563-4981
First Name & Middle Initial & Last Name & Degree
Ali Keshavarzian, MD

12. IPD Sharing Statement

Learn more about this trial

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

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