UMIN-ICDS Clinical Trial
| Unique ID issued by UMIN | UMIN000034715 |
|---|---|
| Receipt number | R000039576 |
| Scientific Title | Impact of inflammatory cytokines to CYP3A or OATP1B activities in rheumatoid arthritis patient using endogenous substrate. |
| Date of disclosure of the study information | 2018/11/12 |
| Last modified on | 2022/05/04 10:33:39 |
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Basic information
Public title
Impact of inflammatory cytokines to CYP3A or OATP1B activities in rheumatoid arthritis patient using endogenous substrate.
Acronym
Impact of inflammatory cytokines to CYP3A or OATP1B activities in rheumatoid arthritis patient using endogenous substrate.
Scientific Title
Impact of inflammatory cytokines to CYP3A or OATP1B activities in rheumatoid arthritis patient using endogenous substrate.
Scientific Title:Acronym
Impact of inflammatory cytokines to CYP3A or OATP1B activities in rheumatoid arthritis patient using endogenous substrate.
Region
| Japan |
Condition
Condition
rheumatoid arthritis
Classification by specialty
| Clinical immunology |
Classification by malignancy
Others
Genomic information
YES
Objectives
Narrative objectives1
We evaluate the correlation between inflammatory cytokine levels and CYP3A or OATP1B activities in RA patients using endogenous substrates, 4beta -OHC or CP-I, respectively.
Basic objectives2
Others
Basic objectives -Others
Rheumatoid arthritis (RA) is one of the systemic inflammatory diseases, which has a major symptom of multiple arthritis and progressive joint destruction. Since the prevalence of RA is high in elderly women, most RA patients have various diseases and take medications such as hypertension and hyperlipidemia. Among these, the agents that are metabolized by CYP3A and/or transported into the liver by OATP1B are included. According to past animal experiment reports, inflammatory cytokines, especially IL-6 and TNF-alpha, which are key factors in the pathogenesis of RA inhibit the expression of CYP3A at the mRNA level by up-regulating inhibitory transcription factors. Recently, coproporphyrin-I (CP-I) was identified as a specific endogenous substrate of OATP1B1 and OATP1B3. Thus, we evaluate the correlation between inflammatory cytokine levels and CYP3A or OATP1B activities in RA patients using endogenous substrates, 4beta-hydroxycholesterol (4beta-OHC) or CP-I, respectively.
Trial characteristics_1
Trial characteristics_2
Developmental phase
Assessment
Primary outcomes
The prospective study will recruit 100 inpatients or outpatients for 18 years of age or over introduced to the Department of Rheumatology, Oita University Faculty of Medicine, who are not in remission state with DAS 28-CRP score (more than 2.3). Genetic polymorphisms of CYP3A or OATP1B was evaluated by identifying genotypes of single nucleotide polymorphism A6986G (CYP3A5*3) or A388G (SLOC1B1*1b) and T521C (SLOC1B1*5), respectively, using real-time PCR. The concentration of 4beta-OHC in plasma was quantified using gas chromatography-mass spectrometry (GC-MS) previously developed. The plasma CP-I concentration was determined using an ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS). The concentrations of inflammatory cytokines (IL-6, TNF-alpha, IL-1beta) in the plasma are measured using each ELISA. The correlation between inflammatory cytokines and plasma 4beta-OHC or CP-I concentration is statistically analyzed using Pearson correlation coefficient or Spearman rank correlation coefficient. Furthermore, using genotypes of CYP3A5*3 or SLOC1B1*1b and SLOC1B1*5, and background, the major factors that influences these concentrations are analyzed by multivariate logistic regression analysis.
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
| 18 | years-old | <= |
Age-upper limit
| Not applicable |
Gender
Male and Female
Key inclusion criteria
RA patients who are not in remission state with DAS 28-CRP (more than 2.3)
Key exclusion criteria
Not applicable
Target sample size
100
Research contact person
Name of lead principal investigator
| 1st name | Ryota |
| Middle name | |
| Last name | Tanaka |
Organization
Oita University Hospital
Division name
Department of Clinical Pharmacy
Zip code
879-5593
Address
1-1 Hasama-machi, Yufu-City Oita 879-5593, Japan.
TEL
0975866113
rtanaka@oita-u.ac.jp
Public contact
Name of contact person
| 1st name | Ryota |
| Middle name | |
| Last name | Tanaka |
Organization
Oita University Hospital
Division name
Department of Clinical Pharmacy
Zip code
879-5593
Address
1-1 Hasama-machi, Yufu-City Oita 879-5593, Japan.
TEL
0975866113
Homepage URL
rtanaka@oita-u.ac.jp
Sponsor or person
Institute
Oita University Hospital, Department of Clinical Pharmacy
Institute
Department
Personal name
Funding Source
Organization
Japan Science and Technology Agency
Organization
Division
Category of Funding Organization
Japanese Governmental office
Nationality of Funding Organization
Other related organizations
Co-sponsor
Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University
Name of secondary funder(s)
IRB Contact (For public release)
Organization
Oita University Faculty of Medicine Ethics Committee
Address
1-1 Hasama-machi, Yufu-City Oita 879-5593, Japan.
Tel
0975865120
syomu@oita-u.ac.jp
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
| 2018 | Year | 11 | Month | 12 | Day |
Related information
URL releasing protocol
Nothing
Publication of results
Unpublished
Result
URL related to results and publications
Nothing
Number of participants that the trial has enrolled
37
Results
37 outpatients with RA were analyzed. OATP1B115 carriers tended to have higher CP-I concentration compared to non-carriers. Plasma CP-I correlated positively with CMPF concentration, but did not correlate with IL-6 or TNF-alpha concentration. Multiple logistic regression analysis by stepwise selection identified plasma CMPF concentration and OATP1B115 allele as significant factors independently affecting plasma CP-I concentration at baseline and at the next visit, respectively.
Results date posted
| 2021 | Year | 05 | Month | 04 | Day |
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics
Thirty-seven outpatients with RA who satisfied the selection criteria were analyzed.
Participant flow
This study was conducted after obtaining approval by the ethics committee of Meiji Pharmaceutical University (approval number: 202017) and the ethics committee of Oita University (approval number: 1433 and P-13-14). Each patient received prior explanations about this study and gave written informed consent.
Adverse events
Nothing
Outcome measures
This study evaluated the influence of several factors comprising gene polymorphisms, uremic toxins and inflammatory cytokines on OATP1B activity using plasma CP-I concentration.
Plan to share IPD
IPD sharing Plan description
Progress
Recruitment status
No longer recruiting
Date of protocol fixation
| 2018 | Year | 10 | Month | 31 | Day |
Date of IRB
| 2018 | Year | 12 | Month | 14 | Day |
Anticipated trial start date
| 2019 | Year | 01 | Month | 14 | Day |
Last follow-up date
| 2019 | Year | 12 | Month | 31 | Day |
Date of closure to data entry
| 2021 | Year | 03 | Month | 31 | Day |
Date trial data considered complete
| 2021 | Year | 03 | Month | 31 | Day |
Date analysis concluded
| 2021 | Year | 03 | Month | 31 | Day |
Other
Other related information
Nothing
Management information
Registered date
| 2018 | Year | 10 | Month | 31 | Day |
Last modified on
| 2022 | Year | 05 | Month | 04 | Day |
Link to view the page
Value
https://center6.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000039576
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