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Chronotherapy of 5-Aminosalicylic Acid in Ulcerative Colitis

Primary Purpose

Ulcerative Colitis

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Chronotherapy
Sponsored by
Rush University Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ulcerative Colitis

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 endogenous melatonin including metoclopramide, NSAIDs, beta blocker, psychotropic medication, hypnotics and exogenous melatonin 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

Sites / Locations

  • Rush University Medical CenterRecruiting
  • The Medical University of South Carolina

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Other

Arm Label

Morning Medication Administration

Night Medication Administration

Arm Description

Subjects are directed to take their medication between 06:00 and 10:00.

Subjects are directed to take their medication between 18:00 and 22:00.

Outcomes

Primary Outcome Measures

Change in Stool Calprotectin from Baseline to Morning Medication Administration to Night Medication Administration
ELISA
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

Secondary Outcome Measures

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.
Change in Serum Cytokines from Baseline to Morning Medication Administration to Night Medication Administration
LBP, LPS, zonulin, and sCD14
Change in Mayo Score from Baseline to Morning Medication Administration to Night Medication Administration
Mayo Score
Change in Circadian Rhythms from Baseline to Morning Medication Administration to Night Medication Administration
Wrist Actigraphy

Full Information

First Posted
December 9, 2021
Last Updated
October 13, 2023
Sponsor
Rush University Medical Center
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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1. Study Identification

Unique Protocol Identification Number
NCT05213234
Brief Title
Chronotherapy of 5-Aminosalicylic Acid in Ulcerative Colitis
Official Title
Chronotherapy of 5-Aminosalicylic Acid in Ulcerative Colitis: A Randomized Crossover Trial
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 9, 2021 (Actual)
Primary Completion Date
April 1, 2024 (Anticipated)
Study Completion Date
September 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Rush University Medical Center
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

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
Data Monitoring Committee
No

5. 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). 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ulcerative Colitis

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
Investigator
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Morning Medication Administration
Arm Type
Other
Arm Description
Subjects are directed to take their medication between 06:00 and 10:00.
Arm Title
Night Medication Administration
Arm Type
Other
Arm Description
Subjects are directed to take their medication between 18:00 and 22:00.
Intervention Type
Behavioral
Intervention Name(s)
Chronotherapy
Intervention Description
Chronotherapy is a behavioral intervention that has the intended effect of maximizing therapeutic benefit of a drug by coordinating intake times and biological rhythms.
Primary Outcome Measure Information:
Title
Change in Stool Calprotectin from Baseline to Morning Medication Administration to Night Medication Administration
Description
ELISA
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
Title
Change in Mucosal 5-ASA Concentration from Baseline to Morning Medication Administration to Night Medication Administration
Description
HPLC of tissue samples taken during flexible sigmoidoscopy at Baseline, Morning Medication Administration and 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
Secondary Outcome Measure Information:
Title
Change in Intestinal Permeability from Baseline to Morning Medication Administration to Night Medication Administration
Description
Intestinal permeability is assessed through spectrophotometric measurements of sucralose, sucrose, maltose and lactulose concentrations in urine following ingestion of a sugar cocktail.
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
Title
Change in Serum Cytokines from Baseline to Morning Medication Administration to Night Medication Administration
Description
LBP, LPS, zonulin, and sCD14
Time Frame
Single blood draw at baseline, single blood draw at Morning Medication Administration, and single blood draw at Night Medication Administration
Title
Change in Mayo Score from Baseline to Morning Medication Administration to Night Medication Administration
Description
Mayo Score
Time Frame
5 minute questionnaire at Baseline, 5 minute questionnaire at Morning Medication Administration, 5 minute questionnaire at Night Medication Administration
Title
Change in Circadian Rhythms from Baseline to Morning Medication Administration to Night Medication Administration
Description
Wrist Actigraphy
Time Frame
Wrist Actigraphy Watch worn for two weeks at Baseline, two weeks at Morning Medication Administration, and two weeks at night medication administration

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: M/F, 18-65 years of age Ulcerative Colitis with Inactive Disease (Mayo Score ≤ 2; partial Mayo Score ≤ 1 with endoscopic score 0-1) Subclinical inflammation (stool calprotectin >50 or CRP > 8 mg/L) Stable medications with no disease flares for the > 3 months Normal psychological evaluation and negative drug screen (See Below) Exclusion Criteria: Active UC at enrollment (Mayo > 2 and/or sigmoidoscopy score of 2 or 3) Prior ostomy or subtotal colectomy Recent prednisone or antibiotic use in last 12 weeks Use of biologic or immunomodulatory medications (i.e. Infliximab, Adalimumab, azathioprine, Vedolizumab, methotrexate, etc.) Major Depression identified as Beck Depression Inventory (score ≥14) Restless leg syndrome (score ≥ 15 on the IRLS Study Group Rating Scale) Sleep apnea (score high risk ≥ 2 or more categories on the Berlin Questionnaire) Clinically significant diabetes (Hgb-A1c>7) Regular use of medications that affect intestinal permeability, intestinal motility and/or NSAIDs, products during 4 weeks prior to the study Atypical American diet (FFQ 5-15 g fiber per day) Clinically significant cardiac, renal (creatinine > twice normal) or liver disease Alcohol use disorder (AUDIT>8) Chronic use of illicit drugs Shift Work Children under 6 months Inability to sign an informed consent
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ali Keshavarzian, M.D.
Phone
312-563-4175
Email
ali_keshavarzian@rush.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Daynia Sanchez-Bass
Phone
(312) 563-4981
Email
Daynia_Sanchez-Bass@rush.edu
Facility Information:
Facility Name
Rush University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60068
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Daynia Sanchez-Bass
Phone
312-563-4981
Email
Daynia_Sanchez-Bass@rush.edu
First Name & Middle Initial & Last Name & Degree
Michelle Villanueva
Phone
312-942-8927
Email
Michelle_Villanueva@rush.edu
Facility Name
The Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Garth R Swanson, M.D.
Phone
843-876-2152
Email
swansong@musc.edu

12. IPD Sharing Statement

Plan to Share IPD
No

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Chronotherapy of 5-Aminosalicylic Acid in Ulcerative Colitis

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