Chronotherapy in Inflammatory Bowel Disease

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04304950

Enrollment

Registered

2020-03-12

Start date

2016-04-25

Completion date

2023-04-30

Last updated

2023-06-27

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Inflammatory Bowel Diseases

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.

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.

Interventions

DRUGEvening Group

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

DRUGMorning Group

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

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Intervention 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.

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Thioguanine Levels in Blood (Morning Versus Evening Dosing)	10 weeks post baseline visit.	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.
Harvey Bradshaw Activity Index	10 weeks post baseline visit.	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.
Short Inflammatory Bowel Disease Questionnaire	10 weeks post baseline visit.	Quality of Life Measure Score:1-7 (The higher the number the greater the quality of life)
6-Methylmercaptopurine Levels in Blood	10 weeks post baseline visit.	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.

Secondary

Measure	Time frame	Description
Munich Chronotype Questionnaire ( MCTQ)	10 weeks post baseline visit.	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.

Countries

United States

Participant flow

Pre-assignment details

Participants were assigned to groups based only on morning vs. evening medication administration status, not on their IBD condition or medication. This study focuses on the timing of medication. It was pre-specified in the protocol to report data based on timing. No plans were made to further stratify the data into more groups. After completing the first research visit, all subjects were asked to take their medication at the opposite time of day from their baseline for 10 weeks.

Participants by arm

Arm	Count
Evening Group Medication Administration Participants with Ulcerative Colitis taking Azathioprine or 6-Mercaptopurine orally once a day. Dosage amount is per clinical care and not defined by the study protocol. Participants with Crohn's Disease taking Azathioprine or 6-Mercaptopurine orally once a day. Dosage amount is per clinical care and not defined by the study protocol. Evening Group: Participants will take their IBD medication (either azathioprine or 6-mercaptopurine) between 6:00 pm and 11:00 pm.	18
Morning Group Medication Administration Participants with Ulcerative Colitis taking 6-Mercatopurine or 6-Mercaptopurine orally once a day. Dosage amount is per clinical care and not defined by the study protocol. Participants with Crohn's Disease taking Azathioprine or 6-Mercaptopurine orally once a day. Dosage amount is per clinical care and not defined by the study protocol. Morning Group: Participants will take their IBD medication (either azathioprine or 6-mercaptopurine) between 6:00 am and 11:00 am.	8
Total	26

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Lost to Follow-up	1	1

Baseline characteristics

Characteristic	Evening Group Medication Administration	Morning Group Medication Administration	Total
Age, Categorical <=18 years	0 Participants	1 Participants	1 Participants
Age, Categorical >=65 years	9 Participants	1 Participants	10 Participants
Age, Categorical Between 18 and 65 years	9 Participants	6 Participants	15 Participants
Age, Continuous	64 years	32.5 years	57 years
Race/Ethnicity, Customized African American	2 Participants	2 Participants	4 Participants
Race/Ethnicity, Customized Asian	0 Participants	1 Participants	1 Participants
Race/Ethnicity, Customized Caucasian	16 Participants	5 Participants	21 Participants
Region of Enrollment United States	18 Participants	8 Participants	26 Participants
Sex: Female, Male Female	12 Participants	2 Participants	14 Participants
Sex: Female, Male Male	6 Participants	6 Participants	12 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 18	0 / 8
other Total, other adverse events	0 / 18	0 / 8
serious Total, serious adverse events	0 / 18	0 / 8

Outcome results

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.