Chronotherapy of 5-Aminosalicylic Acid in Ulcerative Colitis

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 ≤ 1with endoscopic score 0-1)

3. Subclinical inflammation stool calprotectin > 50 or CRP > mg/L above the upper limitof 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 ORA: 20052807-IRB01Date IRB Approved: 11/6/2023 Amendment Date: 4/7/2024 Protocol Version Date: 4/4/2024 7

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 motilityand/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