Chronotherapy in Inflammatory Bowel Disease

Inflammatory Bowel Diseases Clinical Trial

Official title:

Chronotherapy in Inflammatory Bowel Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04304950
• Other study ID #: 16040505
• Status: Completed
• Phase: Phase 4
• Start date: April 25, 2016
• Est. completion date: April 2023

Study information

• Verified date: June 2023
• Source: Rush University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: April 2023
• Est. primary completion date: December 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Inflammatory Bowel Diseases
• Intestinal Diseases

Intervention

Drug:
• Evening Group
Participants will take their IBD medication (either azathioprine or 6-mercaptopurine) between 6:00 pm and 11:00 pm.
• Morning Group
Participants will take their IBD medication (either azathioprine or 6-mercaptopurine) between 6:00 am and 11:00 am.

Locations

Country	Name	City	State
United States	Rush University Medical Center	Chicago	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Rush University Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (7)

Ardizzone S, Bianchi Porro G. Biologic therapy for inflammatory bowel disease. Drugs. 2005;65(16):2253-86. doi: 10.2165/00003495-200565160-00002. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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.
Primary	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.
Primary	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	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.

External 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