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

Tracking Information

• First Submitted Date: December 9, 2021
• First Posted Date: January 28, 2022
• Last Update Posted Date: May 3, 2023
• Actual Study Start Date: July 9, 2021
• Estimated Primary Completion Date: December 31, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 14, 2022)

• 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
• 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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 14, 2022)

• 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.
• 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
• 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
• 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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Chronotherapy of 5-Aminosalicylic Acid in Ulcerative Colitis
• Official Title: Chronotherapy of 5-Aminosalicylic Acid in Ulcerative Colitis: A Randomized Crossover Trial

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).

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Single (Investigator); Primary Purpose: Treatment
• Condition: 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.

Study Arms

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 14, 2022): 60
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 31, 2024
• Estimated Primary Completion Date: December 31, 2023 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

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

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05213234
• Other Study ID Numbers: 20052807
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Ali Keshavarzian, Rush University Medical Center
• Original Responsible Party: Rush University Medical Center
• Current Study Sponsor: Rush University Medical Center
• Original Study Sponsor: Same as current
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Not Provided
• PRS Account: Rush University Medical Center
• Verification Date: May 2023