Chronotherapy of 5-Aminosalicylic Acid in Ulcerative Colitis: A Randomized Crossover Trial
General Information:
The hypothesis of this study is that the appropriate time of day of administration of oral, once-daily 5-ASA therapy in alignment with the participant’s circadian rhythms will improve subclinical inflammation and microbial structure/function and increase mucosal 5-ASA levels.
Eligibility:
Inclusion Criteria:
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Participant between the ages of 18 through 65 years of age
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Ulcerative Colitis with Inactive Disease (Mayo Score ≤ 2; partial Mayo Score ≤ 1 with endoscopic score 0-1)
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Subclinical inflammation (stool calprotectin >50)
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Stable medications with no disease flares for the > 3 months
Exclusion Criteria:
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Active UC at enrollment (Mayo > 2 and/or sigmoidoscopy score of 2 or 3)
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Prior ostomy or subtotal colectomy
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Recent prednisone or antibiotic use in last 12 weeks
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Use of biologic or immunomodulatory medications (i.e. Infliximab, Adalimumab, azathioprine, Vedolizumab, methotrexate, etc.)
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Major Depression identified as Beck Depression Inventory (score ≥14)
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Restless leg syndrome (score ≥ 15 on the IRLS Study Group Rating Scale)
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Sleep apnea (score high risk ≥ 2 or more categories on the Berlin Questionnaire)
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Clinically significant diabetes (Hgb-A1c>7)
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Regular use of medications that affect intestinal permeability, intestinal motility, and/or NSAIDs, during 4 weeks prior to the study
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Atypical American diet (FFQ 5-15 g fiber per day)
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Clinically significant cardiac, renal (creatinine > twice normal) or liver disease
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Alcohol use disorder (AUDIT>8)
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Chronic use of illicit drugs
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Inability to sign an informed consent
Study Details:
Study description:
The study is looking to investigate if there is a benefit to taking Inflammatory Bowel Disease (IBD) medication at a certain time of day. To test this theory the study asks participants who are already taking 5-ASA for IBD to take the medication consistently in either the morning or in the evening based on when they currently take their medication. Participation is up to 6 months and there will be 4 study visits: the first will act as an evaluation for study inclusion and visits 2-4 will consist of answering questionnaires, wearing an actigraphy watch, completing stool collection, flexible sigmoidoscopy, intestine permeability test, and blood draw.
Description of treatment or intervention (mechanism of action):
Participants will be assigned a time (morning or evening) to self-administer their prescribed medication for 6 months. Patients who currently take their medication in the morning will be asked to switch to an evening delivery and patients who currently take their medication at night will be asked to switch to a morning delivery. The group assigned to the morning delivery time will be told to take their medication between 6am and 11am. The group assigned to the evening delivery time will be told to take their medication between 6pm and 11pm.
Patient participation requirements:
As part of the study, participants will be asked to complete the following: 4 blood draws, 3 flexible sigmoidoscopies, 3 stool collection, 3 intestine permeability tests, wear a wrist actigraphy device twice to measure sleeping patterns and questionnaires.
A flexible sigmoidoscopy is a procedure where a doctor will insert a narrow tube with a light and tiny camera into the participant’s colon to evaluate the health of their colon.
An intestine permeability test evaluates how easily their gut absorbs substances by evaluating sugar levels in their urine. Questionnaires cover several topics including GI symptoms, sleep habits, eating habits, and mental health.
Possible risks and side effects:
Phlebotomy (blood draw): There may be some discomfort or bruising on initial insertion of the catheter into a vein but wearing the catheter should not be painful. Occasionally, mild discomfort may occur.
Sigmoidoscopy and Colonic Biopsy: The primary risk for most subjects undergoing sigmoidoscopy and biopsy is minimal discomfort during sigmoidoscopic examination. Risks include discomfort from air being added into the colon, bloating much like gas pain, possible irritation and a small amount of blood loss. The Principal Investigator (PI), Dr. Garth Swanson, who will perform all sigmoidoscopic examinations, is an experienced gastroenterologist with extensive experience in endoscopy over the last 10+ years. If there is evidence of bleeding or perforation, the subject will be admitted to the hospital for observation and additional therapy.
Questionnaires: We have taken steps to reduce the risk of discomfort associated with answering medical/personal questions by keeping an individual’s responses completely confidential (including not sharing an individual’s responses with their physician), allowing participants to leave blank any questions that may make them uncomfortable on any of the forms, and providing brief assessment/counseling by the Division clinical psychologist or PI for any subject who becomes distressed.
The study investigator will review all of the known potential side effects with you to help you determine if you would like to participate in the study.