Chronotherapy in Inflammatory Bowel Disease

NCT ID: NCT04304950

Last Updated: 2023-06-27

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

28 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-04-25

Study Completion Date

2023-04-30

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.

Conditions

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Inflammatory Bowel Diseases

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Morning Group

Intervention Type DRUG

Participants will take their IBD medication (either azathioprine or 6-mercaptopurine) between 6:00 am and 11:00 am.

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.

Group Type EXPERIMENTAL

Evening Group

Intervention Type DRUG

Participants will take their IBD medication (either azathioprine or 6-mercaptopurine) between 6:00 pm and 11:00 pm.

Interventions

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Evening Group

Participants will take their IBD medication (either azathioprine or 6-mercaptopurine) between 6:00 pm and 11:00 pm.

Intervention Type DRUG

Morning Group

Participants will take their IBD medication (either azathioprine or 6-mercaptopurine) between 6:00 am and 11:00 am.

Intervention Type DRUG

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Rush University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Garth Swanson, MD

Associate Professor of Medicine Director, Rush Center of Crohn's & Colitis Director, Clinical Chronobiology Center

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Garth Swanson, MD

Role: PRINCIPAL_INVESTIGATOR

Rush University Medical Center

Locations

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Rush University Medical Center

Chicago, Illinois, United States

Site Status

Countries

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United States

References

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

Reference Type BACKGROUND
PMID: 16266194 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11218242 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22072847 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26596920 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26525013 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23259651 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17978158 (View on PubMed)

Hasskamp J, Meinhardt C, Patton PH, Timmer A. Azathioprine and 6-mercaptopurine for maintenance of remission in ulcerative colitis. Cochrane Database Syst Rev. 2025 Feb 27;2(2):CD000478. doi: 10.1002/14651858.CD000478.pub5.

Reference Type DERIVED
PMID: 40013523 (View on PubMed)

Swanson GR, Biglin M, Raff H, Chouhan V, Jochum S, Shaikh M, Francey L, Bishehsari F, Hogenesch J, Keshavarzian A. Impact of Chronotherapy on 6-Mercaptopurine Metabolites in Inflammatory Bowel Disease: A Pilot Crossover Trial. Clin Transl Gastroenterol. 2023 Feb 1;14(2):e00549. doi: 10.14309/ctg.0000000000000549.

Reference Type DERIVED
PMID: 36730289 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Related Links

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https://www.crohnscolitisfoundation.org/what-is-ibd/medication/immunomodulators

Immunomodulators. (2009, January 16). Retrieved from Crohn's \& Colitis Foundation of America

http://www.cdc.gov/ibd/index.htm

Inflammatory bowel disease. (2014, September 4). Retrieved February 25, 2016, from Centers for Disease Control and Prevention Website

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

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

Other Identifiers

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16040505

Identifier Type: -

Identifier Source: org_study_id

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