Trial Outcomes & Findings for Chronotherapy in Inflammatory Bowel Disease (NCT NCT04304950)

NCT ID: NCT04304950

Last Updated: 2023-06-27

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

28 participants

Primary outcome timeframe

10 weeks post baseline visit.

Results posted on

2023-06-27

Participant Flow

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.

Participant milestones

Participant milestones
Measure
Evening Group Medication Administration
Participants with Ulcerative Colitis or Crohn's Disease taking Azathioprine or 6- Mercaptopurine orally once a day in the morning were assigned to the evening group. 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 for the duration of the study (10 weeks).
Morning Group Administration
Participants with Ulcerative Colitis or Crohn's Disease taking Azathioprine or 6- Mercaptopurine orally once a day in the evening were assigned to the morning intervention group. 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 for the duration of the study (10 weeks)
Overall Study
STARTED
19
9
Overall Study
COMPLETED
18
8
Overall Study
NOT COMPLETED
1
1

Reasons for withdrawal

Reasons for withdrawal
Measure
Evening Group Medication Administration
Participants with Ulcerative Colitis or Crohn's Disease taking Azathioprine or 6- Mercaptopurine orally once a day in the morning were assigned to the evening group. 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 for the duration of the study (10 weeks).
Morning Group Administration
Participants with Ulcerative Colitis or Crohn's Disease taking Azathioprine or 6- Mercaptopurine orally once a day in the evening were assigned to the morning intervention group. 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 for the duration of the study (10 weeks)
Overall Study
Lost to Follow-up
1
1

Baseline Characteristics

Chronotherapy in Inflammatory Bowel Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Evening Group Medication Administration
n=18 Participants
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.
Morning Group Medication Administration
n=8 Participants
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.
Total
n=26 Participants
Total of all reporting groups
Age, Categorical
<=18 years
0 Participants
n=5 Participants
1 Participants
n=7 Participants
1 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
9 Participants
n=5 Participants
6 Participants
n=7 Participants
15 Participants
n=5 Participants
Age, Categorical
>=65 years
9 Participants
n=5 Participants
1 Participants
n=7 Participants
10 Participants
n=5 Participants
Age, Continuous
64 years
n=5 Participants
32.5 years
n=7 Participants
57 years
n=5 Participants
Sex: Female, Male
Female
12 Participants
n=5 Participants
2 Participants
n=7 Participants
14 Participants
n=5 Participants
Sex: Female, Male
Male
6 Participants
n=5 Participants
6 Participants
n=7 Participants
12 Participants
n=5 Participants
Race/Ethnicity, Customized
Caucasian
16 Participants
n=5 Participants
5 Participants
n=7 Participants
21 Participants
n=5 Participants
Race/Ethnicity, Customized
African American
2 Participants
n=5 Participants
2 Participants
n=7 Participants
4 Participants
n=5 Participants
Race/Ethnicity, Customized
Asian
0 Participants
n=5 Participants
1 Participants
n=7 Participants
1 Participants
n=5 Participants
Region of Enrollment
United States
18 Participants
n=5 Participants
8 Participants
n=7 Participants
26 Participants
n=5 Participants

PRIMARY outcome

Timeframe: 10 weeks post baseline visit.

Population: During the analysis, the PI and study team grouped participants by their AM and PM medication administration, regardless of what condition or medication they were on. UC and CD are types of IBD, so the analysis focuses on timing of medication in IBD. Unable to find and recruit UC patients on 6-MP.

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.

Outcome measures

Outcome measures
Measure
Evening Group Medication Administration
n=18 Participants
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.
Morning Group Medication Administration
n=8 Participants
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. Morning Group: Participants will take their IBD medication (either azathioprine or 6-mercaptopurine) between 6:00 am and 11:00 am.
Thioguanine Levels in Blood (Morning Versus Evening Dosing)
175.04 pmol/8 x 10^8 RBC
Standard Deviation 106.89
225.65 pmol/8 x 10^8 RBC
Standard Deviation 155.05

PRIMARY outcome

Timeframe: 10 weeks post baseline visit.

Population: During the analysis, the PI and study team grouped participants by their AM and PM medication administration, regardless of what condition or medication they were on. UC and CD are types of IBD, so the analysis focuses on timing of medication in IBD. Unable to find and recruit UC patients on 6-MP.

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.

Outcome measures

Outcome measures
Measure
Evening Group Medication Administration
n=18 Participants
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.
Morning Group Medication Administration
n=8 Participants
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. Morning Group: Participants will take their IBD medication (either azathioprine or 6-mercaptopurine) between 6:00 am and 11:00 am.
Harvey Bradshaw Activity Index
2.15 units on a scale
Standard Deviation 1.71
3.09 units on a scale
Standard Deviation 2.71

PRIMARY outcome

Timeframe: 10 weeks post baseline visit.

Population: During the analysis participants were grouped by AM and PM administration. UC and CD are types of IBD. The study team was unable to recruit Ulcerative Colitis individuals on 6-MP as was originally intended.

Quality of Life Measure Score:1-7 (The higher the number the greater the quality of life)

Outcome measures

Outcome measures
Measure
Evening Group Medication Administration
n=18 Participants
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.
Morning Group Medication Administration
n=8 Participants
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. Morning Group: Participants will take their IBD medication (either azathioprine or 6-mercaptopurine) between 6:00 am and 11:00 am.
Short Inflammatory Bowel Disease Questionnaire
5.83 units on a scale
Standard Deviation 0.56
5.91 units on a scale
Standard Deviation 0.63

PRIMARY outcome

Timeframe: 10 weeks post baseline visit.

Population: During the analysis, the PI and study team grouped participants by their AM and PM medication administration, regardless of what condition or medication they were on. UC and CD are types of IBD, so the analysis focuses on timing of medication in IBD. Unable to find and recruit UC patients on 6-MP.

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.

Outcome measures

Outcome measures
Measure
Evening Group Medication Administration
n=18 Participants
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.
Morning Group Medication Administration
n=8 Participants
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. Morning Group: Participants will take their IBD medication (either azathioprine or 6-mercaptopurine) between 6:00 am and 11:00 am.
6-Methylmercaptopurine Levels in Blood
2395.27 pmol/8 x 10 ^8 RBC
Standard Deviation 2880.26
825.15 pmol/8 x 10 ^8 RBC
Standard Deviation 1023.34

SECONDARY outcome

Timeframe: 10 weeks post baseline visit.

Population: During the analysis, the PI and study team grouped participants by their AM and PM medication administration, regardless of what condition or medication they were on. UC and CD are types of IBD, so the analysis focuses on timing of medication in IBD. Unable to find and recruit UC patients on 6-MP.

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.

Outcome measures

Outcome measures
Measure
Evening Group Medication Administration
n=18 Participants
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.
Morning Group Medication Administration
n=8 Participants
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. Morning Group: Participants will take their IBD medication (either azathioprine or 6-mercaptopurine) between 6:00 am and 11:00 am.
Munich Chronotype Questionnaire ( MCTQ)
3.70 hours
Standard Deviation 1.09
2.57 hours
Standard Deviation 1.21

Adverse Events

Evening Group Medication Administration

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Morning Group Medication Administration

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Garth R. Swanson

Rush University Medical Center

Phone: 312-563-3871

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place