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Chronotherapy in Inflammatory Bowel Disease

Primary Purpose

Inflammatory Bowel Diseases

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Evening Group
Morning Group
Sponsored by
Rush University Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Inflammatory Bowel Diseases

Eligibility Criteria

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

Inclusion Criteria:

  • Above the ages of 18
  • Diagnosis of Crohn's Disease or Ulcerative Colitis
  • Currently taking azathioprine or 6-mercaptopurine
  • Willing to sign study consent form

Exclusion Criteria:

  • Vulnerable population (pregnant, prisoner, non-English speaking or cognitively impaired)
  • Breastfeeding subject
  • Have a history of complications related to immunomodulatory therapy
  • Participating in other research studies involving research interventions
  • Treated with dual corticosteroid and immunomodulatory therapy

Sites / Locations

  • Rush University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Morning

Evening

Arm Description

Participants with Ulcerative Colitis or Crohn's Disease taking 6-Mercatopurine or Azathioprine orally once a day in the evening were assigned to the morning group. Instead of taking their medication at their usual PM time, they were instructed to take their medications in the morning for the duration of the study-10 weeks. The dosage amount is per clinical care and not defined by the study protocol.

Participants with Ulcerative Colitis or Crohn's Disease taking 6-Mercatopurine or Azathioprine orally once a day in the morning were assigned to the evening group. Instead of taking their medication at their usual AM time, they were instructed to take their medications in the evening for the duration of the study-10 weeks. The dosage amount is per clinical care and not defined by the study protocol.

Outcomes

Primary Outcome Measures

Thioguanine Levels in Blood (Morning Versus Evening Dosing)
This is to examine if the intervention results in a greater level of thioguanine in the participants. If so, the participants are expected to have less symptom severity. Comparing baseline taken at visit one to visit two levels 10 weeks after intervention start.
Harvey Bradshaw Activity Index
Harvey Bradshaw Activity Index has 5 questions. The final score is totaled and will fall into the following categories, which are used to define the severity of the disease: >16 severe diseases, 8-16 moderate disease, 5-7 mild disease, <5 remission. Scores range from 0 ( lowest possible score) to 17.
Short Inflammatory Bowel Disease Questionnaire
Quality of Life Measure Score:1-7 (The higher the number the greater the quality of life)
6-Methylmercaptopurine Levels in Blood
This is to examine if the intervention results in a lower level of 6-Methylmercaptopurine in the participants. If so, the participants are expected to have less symptom severity. Comparing baseline taken at visit one to visit two levels 10 weeks after intervention start.

Secondary Outcome Measures

Munich Chronotype Questionnaire ( MCTQ)
This questionnaire is used to collect primary sleep times, such as bed- and rise-times, including the time a person is fully awake, sleep latency and inertia, in addition to other time points. The MCTQ uses the midpoint of sleep between sleep onset and offset to assess chronotype. Chronotype is your body's natural time to be awake or asleep at certain times. Total scores can range from 16 to 86, with the lowest values representing extreme-late chronotype. For this study corrected midpoint of sleep (MSFc) was calculated. This information is combined to determine the mean time of day at which respondents were more likely to feel most alert. The numbers provided in the outcome measure data table represent time (hour and minute). The hour has been converted to military time and the minutes were converted to decimals.

Full Information

First Posted
August 6, 2019
Last Updated
June 1, 2023
Sponsor
Rush University Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT04304950
Brief Title
Chronotherapy in Inflammatory Bowel Disease
Official Title
Chronotherapy in Inflammatory Bowel Disease
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
April 25, 2016 (Actual)
Primary Completion Date
December 2021 (Actual)
Study Completion Date
April 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Rush University Medical Center

4. Oversight

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

5. Study Description

Brief Summary
This study aims to determine if there is any difference in the efficacy of Inflammatory Bowel Disease (IBD) medication and disease outcomes when taken in the morning or in the evening. The IBD medications being observed are azathioprine and 6-mercaptopurine. The study team believes that there may be a benefit to taking the medication at a certain time of day. To test this theory the study asks participants who are already taking either azathioprine or 6-mercaptopurine for IBD to take the medication consistently at either the morning or in the evening based on when they currently take their medication. Participation is up to 10 weeks +/- 3 days. There will be 2 study visits where the participant will be asked to fill in questionnaires related to their IBD symptoms, their sleep habits, sleep quality, and general health information followed by a blood draw.
Detailed Description
The objective of this study is to determine whether the timing of drug administration to treat inflammatory bowel disease (IBD) has an effect on patient outcomes. Primary objective: Determine whether there is a difference in outcomes seen when patients are assigned to take their prescribed immunomodulator (IM) - either Azathioprine or 6-Mercaptopurine - at either a morning delivery time or evening delivery time. The Investigator hypothesize that administration time of immunomodulators (IMs) during the day can affect the clinical outcomes in IBD patients. Specific Aims Include: Determine whether morning vs. evening dosing of patients' prescribed IMs (either Azathioprine or 6-Mercaptopurine) could affect the subclinical markers of inflammation related to disease. Determine whether morning vs. evening dosing of patients' prescribed IMs (either Azathioprine or 6-Mercaptopurine) could affect endoscopic outcomes. Determine whether morning vs. evening dosing of IMs affect their biochemical side effects, as is routinely monitored as part of the patients' clinical care. Determine if outcomes correlate with patients' chronotype, as determined by standard questionnaires (the Munich Chronotype Questionnaire). Description of Procedures: After signing the informed consent form, subjects will be asked to answer the Inflammatory Bowel Disease Questionnaire (IBDQ), the Munich Chronotype Questionnaire (MCTQ), the Harvey Bradshaw questionnaire, and a demographics survey. All six of these questionnaires are included with this IRB. Next, patients will be assigned a time (morning or evening) to self administer their prescribed medication for 10 weeks. Patients who currently take their medication in the morning will be asked to switch to an evening delivery and patients who currently take their medication at night will be asked to switch to a morning delivery. The group assigned to morning delivery time will be told to take their medication between 6am and 11am. The group assigned to evening delivery time will be told to take their medication between 6pm and 11pm. Lastly, patients will be asked to give a blood sample to test for complete blood count (CBC), comprehensive metabolic panel (CMP), C-reactive protein (CRP), methylmercaptopurine (6-MMP), and thioguanine nucleotides (6-TG). Plasma and serum isolated from the blood sample will be temporarily stored to measure inflammatory cytokines after every 20 subjects complete the study. Within a 6-10 week window, as part of their clinical care, subjects will come in to assess their clinical status while undergoing biochemical monitoring every 2-4 weeks. Data from their endoscopic examination, if done, will also be collected. After 10 weeks, the subjects will be asked to complete the IBDQ and Harvey Bradshaw questionnaire. In addition, a blood sample will be obtained to measure the same metabolite levels and other biochemical indications of disease as stated above. Again, plasma and serum will be isolated from the blood sample and stored.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Inflammatory Bowel Diseases

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Participants will be randomized to one of two groups: Evening Time or Morning Time. Participants are used as their own control. The evening time group will take their medication in the evening and the morning time group will take the medication in the morning.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
28 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Morning
Arm Type
Experimental
Arm Description
Participants with Ulcerative Colitis or Crohn's Disease taking 6-Mercatopurine or Azathioprine orally once a day in the evening were assigned to the morning group. Instead of taking their medication at their usual PM time, they were instructed to take their medications in the morning for the duration of the study-10 weeks. The dosage amount is per clinical care and not defined by the study protocol.
Arm Title
Evening
Arm Type
Experimental
Arm Description
Participants with Ulcerative Colitis or Crohn's Disease taking 6-Mercatopurine or Azathioprine orally once a day in the morning were assigned to the evening group. Instead of taking their medication at their usual AM time, they were instructed to take their medications in the evening for the duration of the study-10 weeks. The dosage amount is per clinical care and not defined by the study protocol.
Intervention Type
Drug
Intervention Name(s)
Evening Group
Intervention Description
Participants will take their IBD medication (either azathioprine or 6-mercaptopurine) between 6:00 pm and 11:00 pm.
Intervention Type
Drug
Intervention Name(s)
Morning Group
Intervention Description
Participants will take their IBD medication (either azathioprine or 6-mercaptopurine) between 6:00 am and 11:00 am.
Primary Outcome Measure Information:
Title
Thioguanine Levels in Blood (Morning Versus Evening Dosing)
Description
This is to examine if the intervention results in a greater level of thioguanine in the participants. If so, the participants are expected to have less symptom severity. Comparing baseline taken at visit one to visit two levels 10 weeks after intervention start.
Time Frame
10 weeks post baseline visit.
Title
Harvey Bradshaw Activity Index
Description
Harvey Bradshaw Activity Index has 5 questions. The final score is totaled and will fall into the following categories, which are used to define the severity of the disease: >16 severe diseases, 8-16 moderate disease, 5-7 mild disease, <5 remission. Scores range from 0 ( lowest possible score) to 17.
Time Frame
10 weeks post baseline visit.
Title
Short Inflammatory Bowel Disease Questionnaire
Description
Quality of Life Measure Score:1-7 (The higher the number the greater the quality of life)
Time Frame
10 weeks post baseline visit.
Title
6-Methylmercaptopurine Levels in Blood
Description
This is to examine if the intervention results in a lower level of 6-Methylmercaptopurine in the participants. If so, the participants are expected to have less symptom severity. Comparing baseline taken at visit one to visit two levels 10 weeks after intervention start.
Time Frame
10 weeks post baseline visit.
Secondary Outcome Measure Information:
Title
Munich Chronotype Questionnaire ( MCTQ)
Description
This questionnaire is used to collect primary sleep times, such as bed- and rise-times, including the time a person is fully awake, sleep latency and inertia, in addition to other time points. The MCTQ uses the midpoint of sleep between sleep onset and offset to assess chronotype. Chronotype is your body's natural time to be awake or asleep at certain times. Total scores can range from 16 to 86, with the lowest values representing extreme-late chronotype. For this study corrected midpoint of sleep (MSFc) was calculated. This information is combined to determine the mean time of day at which respondents were more likely to feel most alert. The numbers provided in the outcome measure data table represent time (hour and minute). The hour has been converted to military time and the minutes were converted to decimals.
Time Frame
10 weeks post baseline visit.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Above the ages of 18 Diagnosis of Crohn's Disease or Ulcerative Colitis Currently taking azathioprine or 6-mercaptopurine Willing to sign study consent form Exclusion Criteria: Vulnerable population (pregnant, prisoner, non-English speaking or cognitively impaired) Breastfeeding subject Have a history of complications related to immunomodulatory therapy Participating in other research studies involving research interventions Treated with dual corticosteroid and immunomodulatory therapy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Garth Swanson, MD
Organizational Affiliation
Rush University Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Rush University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
16266194
Citation
Ardizzone S, Bianchi Porro G. Biologic therapy for inflammatory bowel disease. Drugs. 2005;65(16):2253-86. doi: 10.2165/00003495-200565160-00002.
Results Reference
background
PubMed Identifier
11218242
Citation
Belaiche J, Desager JP, Horsmans Y, Louis E. Therapeutic drug monitoring of azathioprine and 6-mercaptopurine metabolites in Crohn disease. Scand J Gastroenterol. 2001 Jan;36(1):71-6. doi: 10.1080/00365520150218084.
Results Reference
background
PubMed Identifier
22072847
Citation
Bradford K, Shih DQ. Optimizing 6-mercaptopurine and azathioprine therapy in the management of inflammatory bowel disease. World J Gastroenterol. 2011 Oct 7;17(37):4166-73. doi: 10.3748/wjg.v17.i37.4166.
Results Reference
background
PubMed Identifier
26596920
Citation
Grevenitis P, Thomas A, Lodhia N. Medical Therapy for Inflammatory Bowel Disease. Surg Clin North Am. 2015 Dec;95(6):1159-82, vi. doi: 10.1016/j.suc.2015.08.004. Epub 2015 Oct 23.
Results Reference
background
PubMed Identifier
26525013
Citation
Gomez-Gomez GJ, Masedo A, Yela C, Martinez-Montiel Mdel P, Casis B. Current stage in inflammatory bowel disease: What is next? World J Gastroenterol. 2015 Oct 28;21(40):11282-303. doi: 10.3748/wjg.v21.i40.11282.
Results Reference
background
PubMed Identifier
23259651
Citation
Haus E, Sackett-Lundeen L, Smolensky MH. Rheumatoid arthritis: circadian rhythms in disease activity, signs and symptoms, and rationale for chronotherapy with corticosteroids and other medications. Bull NYU Hosp Jt Dis. 2012;70 Suppl 1:3-10.
Results Reference
background
PubMed Identifier
17978158
Citation
Perri D, Cole DE, Friedman O, Piliotis E, Mintz S, Adhikari NK. Azathioprine and diffuse alveolar haemorrhage: the pharmacogenetics of thiopurine methyltransferase. Eur Respir J. 2007 Nov;30(5):1014-7. doi: 10.1183/09031936.00026107.
Results Reference
background
Links:
URL
https://www.crohnscolitisfoundation.org/what-is-ibd/medication/immunomodulators
Description
Immunomodulators. (2009, January 16). Retrieved from Crohn's & Colitis Foundation of America
URL
http://www.cdc.gov/ibd/index.htm
Description
Inflammatory bowel disease. (2014, September 4). Retrieved February 25, 2016, from Centers for Disease Control and Prevention Website
URL
http://www.uptodate.com/contents/6-mercaptopurine-6-mp-metabolite-monitoring-and-tpmt-testing-in-the-treatment-of-inflammatory-bowel-disease-with-6-mp-or-azathioprine
Description
MacDermott, R. P. (2016). 6-mercaptopurine (6-MP) metabolite monitoring and TPMT testingin the treatment of inflammatory bowel disease with 6-MP or azathioprine. RetrievedMarch 6, 2016, from UpToDate website

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Chronotherapy in Inflammatory Bowel Disease

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