UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Analysis of NUDT15 gene polymorphism in inflammatory bowel disease patients
Title of the study (Brief title)	Analysis of NUDT15 gene polymorphism in inflammatory bowel disease patients
Region	Japan

Condition
Condition	inflammatory bowel disease
Classification by specialty	Gastroenterology
Classification by malignancy	Others
Genomic information	YES

Objectives
Narrative objectives1	This study is evaluated relation between the NUDT15,TPMT,MRP4,ITPA gene polymorphism, 6-thioguanine nucleotide(6TGN) concentration and thiopurine-induced leukopenia in the IBD patients treated with Azathioprine(AZA)/6-mercaptopurine(6MP).
Basic objectives2	Bio-availability
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	NUDT15 gene polymorphism is analyzed.And WBC count(2,4,8weeks),Interval from onset of AZA/6MP therapy to leukopenia, AZA/6MP dose is evaluated.
Key secondary outcomes

Base
Study type	Observational

Study design
Basic design
Randomization
Randomization unit
Blinding
Control
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms
Purpose of intervention
Type of intervention
Interventions/Control_1
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	20 years-old <=
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	inflammatory bowel disease(IBD) patients
Key exclusion criteria	1)pregnancy 2)history of drug allergy 3)patients not approving the study consent
Target sample size	200

Research contact person
Name of lead principal investigator	Akira Andoh
Organization	Shiga University of Medical Science
Division name	Division of Gastroenterology
Address	Seta Tsukinowa, Otsu, Shiga
TEL	077-548-2217
Email	andoh@belle.shiga-med.ac.jp

Public contact
Name of contact person	Atsushi Nishida
Organization	Shiga University of Medical Science
Division name	Division of Gastroenterology
Address	Seta Tsukinowa, Otsu, Shiga
TEL	077-548-2217
Homepage URL
Email	atsuda@belle.shiga-med.ac.jp

Sponsor
Institute	Shiga University of Medical Science
Institute
Department

Funding Source
Organization	Shiga University of Medical Science
Organization
Division
Category of Funding Organization	Self funding
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funｄer(s)

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information	2015 Year 08 Month 17 Day

Progress
Recruitment status	Main results already published
Date of protocol fixation	2015 Year 06 Month 01 Day
Anticipated trial start date	2015 Year 06 Month 10 Day
Last follow-up date
Date of closure to data entry
Date trial data considered complete
Date analysis concluded	2016 Year 04 Month 01 Day

Related information
URL releasing protocol
Publication of results	Published
URL releasing results	http://www.ncbi.nlm.nih.gov/pubmed/26590936
Results	The NUDT15 C/C, C/T, and T/T genotypes were 80.7, 18.2, and 1.1%, respectively.The allelic frequency was 10.2%. Among 161 IBD patients, there was no significant difference in 6-TGN levels among the NUDT15 genotypes.Forty-five patients (27.9%) developed leukocytopenia (WBC<3000/ul), and the C/T and T/T genotypes were significantly associated with the development of leukocytopenia (P=1.7 X 10(-5)). )). In these patients, 6-TGN levels were not significantly different between NUDT15 genotypes. NUDT15 R139C was significantly associated with early (<8 weeks) (P = 1.03 X 10(-4)) and late (>8 weeks) leukocytopenia (P = 4.3 X 10(-4)). The decrease in WBC count at 2 and 4 weeks was significantly higher in patients with the C/T or T/T genotypes as compared to the patients with the C/C genotype. All patients with the T/T genotype (n = 2) developed early severe hair loss and severe leukocytopenia (<1000/ul). The logistic regression analysis revealed that NUDT15 R139C was the sole genetic factor responsible for the thiopurine-induced leukocytopenia (P = 0.001).
Other related information	Retrospective study. This study is evaluated relation between the NUDT15,TPMT,MRP4,ITPA gene polymorphism, AZA/6MP dose, 6TGN concentration and thiopurine-induced leukopenia in the IBD patients treated with Azathioprine(AZA)/6-mercaptopurine(6MP).

Management information
Registered date	2015 Year 08 Month 14 Day
Last modified on	2016 Year 08 Month 15 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000021608