Clinical trial NCT05180279: 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
Overall status: COMPLETED
Phase: NA
Conditions: Ulcerative Colitis
Keywords: Circadian Rhythms
Lead sponsor: Rush University Medical Center
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2022-01-06
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention 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.
Primary purpose: BASIC_SCIENCE

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.


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

Primary outcomes:
measure: Change in the Phase Angle of Entrainment from Baseline (Aligned Circadian Rhythms) to Circadian Misalignment
timeFrame: Blood drawn hourly for eight hours at baseline circadian rhythm (eight draws) and blood drawn hourly for twelve hours at circadian misalignment (12 draws).
measure: Change in Intestinal Permeability from Baseline (Aligned Circadian Rhythms) to Circadian Misalignment
timeFrame: 24 hour urine collection beginning at baseline and 24 hour urine collection at circadian misalignment.
Secondary outcomes:
measure: Change in 24 hour Urinary Melatonin Concentrations from Baseline (Aligned Circadian Rhythms) to Circadian Misalignment
timeFrame: 24 hour urine collection at baseline and 24 hour urine collection at circadian misalignment circadian
measure: Change in Mayo Score from Baseline (Aligned Circadian Rhythms) to Circadian Misalignment
timeFrame: 30 minute flexible sigmoidoscopy at Baseline and 30 minute flexible sigmoidoscopy at Circadian Misalignment
measure: Change in Stool Calprotectin from Baseline (Aligned Circadian Rhythms) to Circadian Misalignment
timeFrame: 10 minute stool collection conducted at baseline circadian rhythm and at circadian misalignment.
measure: Change in Concentration of Serum Cytokine Markers of Inflammation from Baseline (Aligned Circadian Rhythms) to Circadian Misalignment
timeFrame: 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
measure: Changes in Clock Gene Expression in Peripheral Blood Mononuclear Cells from Baseline (Aligned Circadian Rhythms) to Circadian Misalignment
timeFrame: 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
measure: Changes in Gene Expression of Colonic Tissue Biopsies from Baseline (Aligned Circadian Rhythms) to Circadian Misalignment
timeFrame: 30 minute flexible sigmoidoscopy at Baseline and 30 minute flexible sigmoidoscopy at Circadian Misalignment
Other outcomes:
measure: Diet
timeFrame: Once before sleep lab
measure: Single day food recall
timeFrame: Once before sleep lab
measure: Chronotype
timeFrame: Screening
measure: Inflammatory Bowel Disease Questionnaire
timeFrame: Screening
measure: Beck Depression Inventory
timeFrame: 3 Weeks prior to circadian lab assessments
measure: The State-Trait Anxiety Inventory
timeFrame: Screening
measure: Perceived Stress Questionnaire
timeFrame: Screening
measure: The International Restless Legs Syndrome Study Group Rating Scale
timeFrame: Screening
measure: Berlin Questionnaire
timeFrame: Screening
measure: Pittsburgh Sleep Quality Index
timeFrame: 3 Weeks prior to circadian lab assessments
Locations:
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
Study officials:
References: