Chronotherapy of 5-Aminosalicylic Acid in Ulcerative Colitis

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

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.

Study Overview

• Status: Recruiting
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Behavioral: Chronotherapy

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Daynia Sanchez-Bass; Phone Number: (312) 563-4981; Email: Daynia_Sanchez-Bass@rush.edu
• Study Contact Backup: Name: Ali Keshavarzian, M.D.; Phone Number: 312-563-4175; Email: ali_keshavarzian@rush.edu

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60068
      • Recruiting
      • Rush University Medical Center
      • Contact: Michelle Villanueva; Phone Number: 312-942-8927; Email: Michelle_Villanueva@rush.edu
      • Contact: Daynia Sanchez-Bass; Phone Number: 312-563-4981; Email: Daynia_Sanchez-Bass@rush.edu
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Not yet recruiting
      • The Medical University of South Carolina
      • Contact: Garth R Swanson, M.D.; Phone Number: 843-876-2152; Email: swansong@musc.edu

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 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.
Other: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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

Collaborators and Investigators

• Sponsor: Rush University Medical Center
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Study record dates

Study Major Dates

• Study Start (Actual): July 9, 2021
• Primary Completion (Estimated): October 31, 2024
• Study Completion (Estimated): October 31, 2024

Study Registration Dates

• First Submitted: December 9, 2021
• First Submitted That Met QC Criteria: January 14, 2022
• First Posted (Actual): January 28, 2022

Study Record Updates

• Last Update Posted (Actual): January 30, 2024
• Last Update Submitted That Met QC Criteria: January 26, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: 20052807

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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