Chronotherapy in Inflammatory Bowel Disease

Study Overview
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Brief Summary
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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
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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.

Official Title
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Chronotherapy in Inflammatory Bowel Disease

Conditions
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Inflammatory Bowel Diseases

Intervention / Treatment
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* Drug: Evening Group
* Drug: Morning Group


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Morning<br>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. | Drug: Morning Group<br>* Participants will take their IBD medication (either azathioprine or 6-mercaptopurine) between 6:00 am and 11:00 am.<br>|
| Experimental: Evening<br>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. | Drug: Evening Group<br>* Participants will take their IBD medication (either azathioprine or 6-mercaptopurine) between 6:00 pm and 11:00 pm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 10 weeks post baseline visit. | 
| 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. | 10 weeks post baseline visit. | 
| Short Inflammatory Bowel Disease Questionnaire | Quality of Life Measure Score:1-7 (The higher the number the greater the quality of life) | 10 weeks post baseline visit. | 
| 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. | 10 weeks post baseline visit. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 10 weeks post baseline visit. |