Chronotherapy of 5-Aminosalicylic Acid in Ulcerative Colitis

Not Applicable

Active, not recruiting

• Conditions: Ulcerative Colitis
• Interventions: Behavioral: Chronotherapy

• Registration Number: NCT05213234
• Lead Sponsor: Rush University Medical Center

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2021-07-09
• Study First Submitted: 2021-12-09
• Study First Submitted QC: 2022-01-14
• Study First Posted: 2022-01-28
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-02
• Last Update Posted: 2025-05-04
• Primary Completion: 2026-03-31
• Study Completion: 2026-03-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 32

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Morning Medication Administration	Chronotherapy	Subjects are directed to take their medication between 06:00 and 10:00.
Night Medication Administration	Chronotherapy	Subjects are directed to take their medication between 18:00 and 22:00.

Primary Outcome Measures

Name	Time	Method
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
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

Secondary Outcome Measures

Name	Time	Method
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
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

Trial Locations

Locations (2)

Rush University Medical Center; 🇺🇸 Chicago, Illinois, United States

The Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States