Clinical trial NCT05213234: Chronotherapy of 5-Aminosalicylic Acid in Ulcerative Colitis
Official title: Chronotherapy of 5-Aminosalicylic Acid in Ulcerative Colitis: A Randomized Crossover Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Ulcerative Colitis
Lead sponsor: Rush University Medical Center
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2022-01-28
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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: 1) 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). 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.


Eligibility criteria: 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 ORA: 20052807-IRB01 Date 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 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

Primary outcomes:
measure: Change in Stool Calprotectin from Baseline to Morning Medication Administration to Night Medication Administration
timeFrame: 10 minute stool collection at Baseline, 10 minute stool collection at Morning Medication Administration, and 10 minute stool collection at Night Medication Administration
measure: Change in Mucosal 5-ASA Concentration from Baseline to Morning Medication Administration to Night Medication Administration
timeFrame: 30 minute flexible sigmoidoscopy at Baseline, 30 minute flexible sigmoidoscopy at Morning Medication Administration, and 30 minute flexible sigmoidoscopy at Night Medication Administration
Secondary outcomes:
measure: Change in Intestinal Permeability from Baseline to Morning Medication Administration to Night Medication Administration
timeFrame: 24 hour urine collection at baseline, 24 hour urine collection at Morning Medication Administration, and 24 hour urine collection at Night Medication Administration
measure: Change in Serum Cytokines from Baseline to Morning Medication Administration to Night Medication Administration
timeFrame: Single blood draw at baseline, single blood draw at Morning Medication Administration, and single blood draw at Night Medication Administration
measure: Change in Mayo Score from Baseline to Morning Medication Administration to Night Medication Administration
timeFrame: 5 minute questionnaire at Baseline, 5 minute questionnaire at Morning Medication Administration, 5 minute questionnaire at Night Medication Administration
measure: Change in Circadian Rhythms from Baseline to Morning Medication Administration to Night Medication Administration
timeFrame: Wrist Actigraphy Watch worn for two weeks at Baseline, two weeks at Morning Medication Administration, and two weeks at night medication administration
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Charleston
country: United States
facility: The Medical University of South Carolina
state: South Carolina
Study officials:
References: