Chronotherapy of 5-Aminosalicylic Acid in Ulcerative Colitis
Study Details
Study Description
Brief Summary
The hypothesis of this study is that appropriate time of day of administration of oral, once daily 5-ASA therapy in alignment with the host circadian rhythms will improve subclinical inflammation and microbial structure/function and increase mucosal 5-ASA levels.
All subjects will be randomized to once daily 5-ASA medications at two different times of the day: between 06:00 - 10:00 h or 18:00 - 22:00 h. Three disease assessments will performed at:
- enrollment just before randomization; 2) month 3, at the completion of first arm (Condition 1), and 3) month 6, after completion of the second arm (Condition 2).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Other: Morning Medication Administration Subjects are directed to take their medication between 06:00 and 10:00. |
Behavioral: Chronotherapy
Chronotherapy is a behavioral intervention that has the intended effect of maximizing therapeutic benefit of a drug by coordinating intake times and biological rhythms.
|
| Other: Night Medication Administration Subjects are directed to take their medication between 18:00 and 22:00. |
Behavioral: Chronotherapy
Chronotherapy is a behavioral intervention that has the intended effect of maximizing therapeutic benefit of a drug by coordinating intake times and biological rhythms.
|
Outcome Measures
Primary Outcome Measures
- Change in Stool Calprotectin from Baseline to Morning Medication Administration to Night Medication Administration [10 minute stool collection at Baseline, 10 minute stool collection at Morning Medication Administration, and 10 minute stool collection at Night Medication Administration]
ELISA
- Change in Mucosal 5-ASA Concentration from Baseline to Morning Medication Administration to Night Medication Administration [30 minute flexible sigmoidoscopy at Baseline, 30 minute flexible sigmoidoscopy at Morning Medication Administration, and 30 minute flexible sigmoidoscopy at Night Medication Administration]
HPLC of tissue samples taken during flexible sigmoidoscopy at Baseline, Morning Medication Administration and Night Medication Administration
Secondary Outcome Measures
- Change in Intestinal Permeability from Baseline to Morning Medication Administration to Night Medication Administration [24 hour urine collection at baseline, 24 hour urine collection at Morning Medication Administration, and 24 hour urine collection at Night Medication Administration]
Intestinal permeability is assessed through spectrophotometric measurements of sucralose, sucrose, maltose and lactulose concentrations in urine following ingestion of a sugar cocktail.
- Change in Serum Cytokines from Baseline to Morning Medication Administration to Night Medication Administration [Single blood draw at baseline, single blood draw at Morning Medication Administration, and single blood draw at Night Medication Administration]
LBP, LPS, zonulin, and sCD14
- Change in Mayo Score from Baseline to Morning Medication Administration to Night Medication Administration [5 minute questionnaire at Baseline, 5 minute questionnaire at Morning Medication Administration, 5 minute questionnaire at Night Medication Administration]
Mayo Score
- Change in Circadian Rhythms from Baseline to Morning Medication Administration to Night Medication Administration [Wrist Actigraphy Watch worn for two weeks at Baseline, two weeks at Morning Medication Administration, and two weeks at night medication administration]
Wrist Actigraphy
Eligibility Criteria
Criteria
Inclusion Criteria:
-
M/F, 18-65 years of age
-
Ulcerative Colitis with Inactive Disease (Mayo Score ≤ 2; partial Mayo Score ≤ 1 with endoscopic score 0-1)
-
Subclinical inflammation (stool calprotectin >50 or CRP > 8 mg/L)
-
Stable medications with no disease flares for the > 3 months
-
Normal psychological evaluation and negative drug screen (See Below)
Exclusion Criteria:
-
Active UC at enrollment (Mayo > 2 and/or sigmoidoscopy score of 2 or 3)
-
Prior ostomy or subtotal colectomy
-
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.)
-
Major Depression identified as Beck Depression Inventory (score ≥14)
-
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 endogenous melatonin including metoclopramide, NSAIDs, beta blocker, psychotropic medication, hypnotics and exogenous melatonin products 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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Shift Work
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Children under 6 months
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Inability to sign an informed consent
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Rush University Medical Center | Chicago | Illinois | United States | 60068 |
Sponsors and Collaborators
- Rush University Medical Center
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 20052807