Chronotherapy of 5-Aminosalicylic Acid in Ulcerative Colitis

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: 1) enrollment just before randomization; 2) month 1, at the completion of first arm (Condition 1), and 3) month 3, after completion of the second arm (Condition 2). During these study time points, participants will be asked to complete questionnaires, track their 5-ASA medication usage, provide a stool sample, blood draw, urine test, collect saliva, wear a watch to measure sleep patterns, and complete a flexible sigmoidoscopy.

Inclusion Criteria: Study will include individuals that are; 1. M/F, 18-65 years of age 2. Ulcerative Colitis with Inactive Disease (Mayo Score ≤ 2; partial Mayo Score ≤ 1 with endoscopic score 0-1) 3. Subclinical inflammation stool calprotectin \> 50 or CRP \> mg/L above the upper limit of normal or PROMIS Fatigue Score ≥ 50) 4. Stable medications with no disease flares for the \> 3 months, Exclusion Criteria: Study will not include individuals that are; 1. Active UC at enrollment (Mayo \> 2 and/or sigmoidoscopy score of 2 or 3) 2. Regular use of suppositories or enemas within the last 3 months 3. Use of biologics or immunomodulatory medications ( i.e. infliximab, Adalimumab, azathioprine, Vedolizumab, methotrexate, etc.) 4. Prior ostomy or subtotal colectomy 5. Recent prednisone or antibiotic use in last 12 weeks 6. Major Depression identified as Beck Depression Inventory (score ≥21) 7. Restless leg syndrome (score ≥ 15 on the IRLS Study Group Rating Scale) 8. Sleep apnea (score high risk ≥ 2 or more categories on the Berlin Questionnaire) 9. Clinically significant diabetes (Hgb-A1c\>7) 10. Regular use of medications that affect intestinal permeability, intestinal motility and/or NSAIDs 4 weeks prior to the study 11. Clinically significant cardiac, renal (creatinine \> twice normal) or liver disease 12. Alcohol use disorder (AUDIT\>8) 13. Chronic use of illicit drugs 14. Shift Work 15. Inability to sign an informed consen