Chronotherapy of 5-Aminosalicylic Acid in Ulcerative Colitis

• ClinicalTrials.gov Identifier: NCT05213234
• Recruitment Status: Recruiting
• First Posted: January 28, 2022
• Last Update Posted: May 3, 2023
• Sponsor: Rush University Medical Center
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Information provided by (Responsible Party): Ali Keshavarzian, Rush University Medical Center

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Ulcerative Colitis	Behavioral: Chronotherapy	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Investigator)
• Primary Purpose: Treatment
• Official Title: Chronotherapy of 5-Aminosalicylic Acid in Ulcerative Colitis: A Randomized Crossover Trial
• Actual Study Start Date: July 9, 2021
• Estimated Primary Completion Date: December 31, 2023
• Estimated Study Completion Date: March 31, 2024

Arms and Interventions

Arm	Intervention/treatment
Morning Medication Administration; Subjects are directed to take their medication between 06:00 and 10:00.	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.
Night Medication Administration; Subjects are directed to take their medication between 18:00 and 22:00.	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.

Outcome Measures

Primary Outcome Measures :

1. Change in Stool Calprotectin from Baseline to Morning Medication Administration to Night Medication Administration [ Time Frame: 10 minute stool collection at Baseline, 10 minute stool collection at Morning Medication Administration, and 10 minute stool collection at Night Medication Administration ]
   ELISA
2. Change in Mucosal 5-ASA Concentration from Baseline to Morning Medication Administration to Night Medication Administration [ Time Frame: 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

Secondary Outcome Measures :

1. Change in Intestinal Permeability from Baseline to Morning Medication Administration to Night Medication Administration [ Time Frame: 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.
2. Change in Serum Cytokines from Baseline to Morning Medication Administration to Night Medication Administration [ Time Frame: 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
3. Change in Mayo Score from Baseline to Morning Medication Administration to Night Medication Administration [ Time Frame: 5 minute questionnaire at Baseline, 5 minute questionnaire at Morning Medication Administration, 5 minute questionnaire at Night Medication Administration ]
   Mayo Score
4. Change in Circadian Rhythms from Baseline to Morning Medication Administration to Night Medication Administration [ Time Frame: Wrist Actigraphy Watch worn for two weeks at Baseline, two weeks at Morning Medication Administration, and two weeks at night medication administration ]
   Wrist Actigraphy

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

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 > 8 mg/L)
4. Stable medications with no disease flares for the > 3 months
5. Normal psychological evaluation and negative drug screen (See Below)

Exclusion Criteria:

1. Active UC at enrollment (Mayo > 2 and/or sigmoidoscopy score of 2 or 3)
2. Prior ostomy or subtotal colectomy
3. Recent prednisone or antibiotic use in last 12 weeks
4. Use of biologic or immunomodulatory medications (i.e. Infliximab, Adalimumab, azathioprine, Vedolizumab, methotrexate, etc.)
5. Major Depression identified as Beck Depression Inventory (score ≥14)
6. Restless leg syndrome (score ≥ 15 on the IRLS Study Group Rating Scale)
7. Sleep apnea (score high risk ≥ 2 or more categories on the Berlin Questionnaire)
8. Clinically significant diabetes (Hgb-A1c>7)
9. Regular use of medications that affect intestinal permeability, intestinal motility and/or NSAIDs, products during 4 weeks prior to the study
10. Atypical American diet (FFQ 5-15 g fiber per day)
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. Children under 6 months
16. Inability to sign an informed consent

Contacts and Locations

Contacts

Contact: Garth R Swanson, M.D.; 312-563-3871; garth_swanson@rush.edu

Contact: Daynia Sanchez-Bass; (312) 563-4981; Daynia_Sanchez-Bass@rush.edu

Locations

United States, Illinois

Rush University Medical Center; Recruiting

Chicago, Illinois, United States, 60068

Contact: Daynia Sanchez-Bass 312-563-4981 Daynia_Sanchez-Bass@rush.edu

Contact: Michelle Villanueva 312-942-8927 Michelle_Villanueva@rush.edu

Sponsors and Collaborators

Rush University Medical Center

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

More Information

• Responsible Party: Ali Keshavarzian, chief of the Section of Gastroenterology, Rush University Medical Center
• ClinicalTrials.gov Identifier: NCT05213234
• Other Study ID Numbers: 20052807
• First Posted: January 28, 2022
• Last Update Posted: May 3, 2023
• Last Verified: May 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Colitis; Colitis, Ulcerative; Ulcer; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Colonic Diseases; Intestinal Diseases; Pathologic Processes; Inflammatory Bowel Diseases