Tailored Therapeutic Model According to the Expression of Genes in Inflammatory Bowel Disease Patients

Effectiveness of Tailored Therapeutic Model According to the Expression of Genes Related to Immunomodulator-induced Myelosuppression in Inflammatory Bowel Disease Patients

This study is a randomized controlled study conducted at five tertiary university hospitals. Patients who are 20-80 years old, diagnosed as having Inflammatory Bowel Disease(IBD) and who are planned to start thiopurines for the first time for the treatment of IBD are enrolled. Patients are assigned to the genotyping group or to the non-genotyping group. The patients who carry any heterozygotic variant among the three genes receive 50 mg azathioprine (AZA) or 25 mg of 6-mercaptopurine, while those who have any homozygotic variant are recommended to take other alternative drugs. The patients who do not carry any genetic variant or are assigned in non-genotyping group receive the standard dose of thiopurines based on the conventional approach.

Patients in the non-genotyping group receive the standard dose of thiopurines based on the conventional approach.

Study Overview

• Status: Completed
• Conditions: Inflammatory Bowel Diseases
• Intervention / Treatment: Genetic: genotyping for three genes (TPMT, NUDT15 and FTO); Other: non-genotyping

• Study Type: Interventional
• Enrollment (Actual): 215
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Seoul National University Hospital
  • Seoul, Korea, Republic of
    • Gangnam Severance Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital
  • Seoul, Korea, Republic of
    • Korea University Hospital
  • Seoul, Korea, Republic of
    • Ewha Medical Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 20-80 years old
• Patients who were diagnosed as having IBD based on clinical, endoscopic, radiographic, and histological assessments,
• Patients who were planned to start thiopurines for the first time for the treatment of IBD.

Exclusion Criteria:

• Patients who had previous use of thiopurine
• Those who had abnormal laboratory findings prior to screening, including white blood cell (WBC) count < 3,000/μL, platelet (PLT) count < 100/μL, or elevation of aminotransferase more than twice the upper normal limits
• Those who were diagnosed other infectious diseases at the time of screening or receiving antibiotics within the previous 7 days;
• Those who were pregnant or lactating.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Genotyping group; The patients undergo pretreatment of genotyping for three genes (TPMT, NUDT15 and FTO)	Genetic: genotyping for three genes (TPMT, NUDT15 and FTO); Patients who carry any heterozygotic variants receive 50 mg AZA or 25 mg 6-mercaptopurine (6-MP), while those who have any homozygotic variants are recommended to take other alternative drugs instead of thiopurines
ACTIVE_COMPARATOR: Non-genotyping group; Patients receive standard doses of thiopurines based on the conventional regimen without pretreatment genotyping.	Other: non-genotyping; Patients receive standard doses of thiopurines based on the conventional regimen without pretreatment genotyping. Conventional regimen starts with 50 mg of AZA, then the dose is increased by 25 mg in every 1-2 weeks to 2.0-2.5 mg/kg along with regular monitoring of general blood tests including WBC counts.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cumulative incidence of myelosuppression	1 year

Collaborators and Investigators

• Sponsor: Yonsei University
• Investigators: Principal Investigator: Jae Hee Cheon, MD, Severance Hospital

Publications and helpful links

General Publications

• Chang JY, Park SJ, Jung ES, Jung SA, Moon CM, Chun J, Park JJ, Kim ES, Park Y, Kim TI, Kim WH, Cheon JH. Genotype-based Treatment With Thiopurine Reduces Incidence of Myelosuppression in Patients With Inflammatory Bowel Diseases. Clin Gastroenterol Hepatol. 2020 Aug;18(9):2010-2018.e2. doi: 10.1016/j.cgh.2019.08.034. Epub 2019 Aug 22.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2016
• Primary Completion (ACTUAL): September 30, 2018
• Study Completion (ACTUAL): October 5, 2018

Study Registration Dates

• First Submitted: October 23, 2018
• First Submitted That Met QC Criteria: October 23, 2018
• First Posted (ACTUAL): October 25, 2018

Study Record Updates

• Last Update Posted (ACTUAL): October 25, 2018
• Last Update Submitted That Met QC Criteria: October 23, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Intestinal Diseases
• Other Study ID Numbers: 4-2015-0812

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Undecided yet.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No