Chronotherapy in Inflammatory Bowel Disease

NCT04304950 | Completed Phase 4 Results FDA Drug

• 1 other identifier: 16040505
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

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.

Conditions

Inflammatory Bowel Diseases

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (1)

• Munich Chronotype Questionnaire ( MCTQ)

  10 weeks post baseline visit.

Study Arms (2)

Morning

EXPERIMENTAL

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

Evening

EXPERIMENTAL

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

Interventions

Evening Group DRUG

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

Evening

Morning Group DRUG

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

Morning

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Rush University Medical Center: lead

Study Sites (1)

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Related Publications (9)

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

  PMID: 16266194 BACKGROUND

• 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.

  PMID: 11218242 BACKGROUND

• 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.

  PMID: 22072847 BACKGROUND

• 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.

  PMID: 26596920 BACKGROUND

• 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.

  PMID: 26525013 BACKGROUND

• 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.

  PMID: 23259651 BACKGROUND

• 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.

  PMID: 17978158 BACKGROUND

• 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.

  PMID: 40013523 DERIVED

• 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.

  PMID: 36730289 DERIVED

Related 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

MeSH Terms

Conditions

Inflammatory Bowel Diseases

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Limitations and Caveats

This was a single-center study with a limited number of IBD subjects that focused on metabolite levels and not clinical efficacy. Larger multicenter studies are needed since this was a "proof of concept" pilot study. Second, the overall dose of AZA/6-MP used in this study was low. Third, the study design relied on patient compliance with medication timing and circadian rhythms were assessed only by questionnaires.

Results Point of Contact

• Title: Dr. Garth R. Swanson
• Organization: Rush University Medical Center

Garth_Swanson@rush.edu

312-563-3871

Study Officials

• Garth Swanson, MD

  Rush University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine Director, Rush Center of Crohn's & Colitis Director, Clinical Chronobiology Center

Model Details: 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.

Study Record Dates

• First Submitted: August 6, 2019
• First Posted: March 12, 2020
• Study Start: April 25, 2016
• Primary Completion: December 1, 2021
• Study Completion: April 1, 2023
• Last Updated: June 27, 2023
• Results First Posted: June 27, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)