Chronotherapy of 5-Aminosalicylic Acid in Ulcerative Colitis

Ulcerative Colitis Clinical Trial

Official title:

Chronotherapy of 5-Aminosalicylic Acid in Ulcerative Colitis: A Randomized Crossover Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05213234
• Other study ID #: 20052807
• Status: Recruiting
• Phase: N/A
• Start date: July 9, 2021
• Est. completion date: October 31, 2024

Study information

• Verified date: April 2024
• Source: Rush University Medical Center
• Contact: Ali Keshavarzian, M.D.
• Phone: 312-563-4175
• Email: ali_keshavarzian[@]rush.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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, wear a watch to measure sleep patterns, and complete a flexible sigmoidoscopy.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: October 31, 2024
• Est. primary completion date: October 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

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.

Locations

Country	Name	City	State
United States	The Medical University of South Carolina	Charleston	South Carolina
United States	Rush University Medical Center	Chicago	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Rush University Medical Center	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Stool Calprotectin from Baseline to Morning Medication Administration to Night Medication Administration	ELISA	10 minute stool collection at Baseline, 10 minute stool collection at Morning Medication Administration, and 10 minute stool collection at Night Medication Administration
Primary	Change in Mucosal 5-ASA Concentration from Baseline to Morning Medication Administration to Night Medication Administration	HPLC of tissue samples taken during flexible sigmoidoscopy at Baseline, Morning Medication Administration and 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
Secondary	Change in Intestinal Permeability from Baseline to Morning Medication Administration to 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.	24 hour urine collection at baseline, 24 hour urine collection at Morning Medication Administration, and 24 hour urine collection at Night Medication Administration
Secondary	Change in Serum Cytokines from Baseline to Morning Medication Administration to Night Medication Administration	LBP, LPS, zonulin, and sCD14	Single blood draw at baseline, single blood draw at Morning Medication Administration, and single blood draw at Night Medication Administration
Secondary	Change in Mayo Score from Baseline to Morning Medication Administration to Night Medication Administration	Mayo Score	5 minute questionnaire at Baseline, 5 minute questionnaire at Morning Medication Administration, 5 minute questionnaire at Night Medication Administration
Secondary	Change in Circadian Rhythms from Baseline to Morning Medication Administration to Night Medication Administration	Wrist Actigraphy	Wrist Actigraphy Watch worn for two weeks at Baseline, two weeks at Morning Medication Administration, and two weeks at night medication administration