- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04304950
Chronotherapy in Inflammatory Bowel Disease
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
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Illinois
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Chicago, Illinois, United States, 60612
- Rush University Medical Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Morning
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.
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Participants will take their IBD medication (either azathioprine or 6-mercaptopurine) between 6:00 am and 11:00 am.
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Experimental: Evening
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.
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Participants will take their IBD medication (either azathioprine or 6-mercaptopurine) between 6:00 pm and 11:00 pm.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Short Inflammatory Bowel Disease Questionnaire
Time Frame: 10 weeks post baseline visit.
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Quality of Life Measure Score:1-7 (The higher the number the greater the quality of life)
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10 weeks post baseline visit.
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Thioguanine Levels in Blood (Morning Versus Evening Dosing)
Time Frame: 10 weeks post baseline visit.
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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.
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10 weeks post baseline visit.
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Harvey Bradshaw Activity Index
Time Frame: 10 weeks post baseline visit.
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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.
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10 weeks post baseline visit.
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6-Methylmercaptopurine Levels in Blood
Time Frame: 10 weeks post baseline visit.
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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.
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10 weeks post baseline visit.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Munich Chronotype Questionnaire ( MCTQ)
Time Frame: 10 weeks post baseline visit.
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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.
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10 weeks post baseline visit.
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Garth Swanson, MD, Rush University Medical Center
Publications and helpful links
General Publications
- Ardizzone S, Bianchi Porro G. Biologic therapy for inflammatory bowel disease. Drugs. 2005;65(16):2253-86. doi: 10.2165/00003495-200565160-00002.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Helpful Links
- Immunomodulators. (2009, January 16). Retrieved from Crohn's & Colitis Foundation of America
- Inflammatory bowel disease. (2014, September 4). Retrieved February 25, 2016, from Centers for Disease Control and Prevention Website
- 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
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 16040505
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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