Functional Genetic Variants Affecting Tacrolimus Trough Levels and Side Effects in Chinese Renal Transplantation.
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|ClinicalTrials.gov Identifier: NCT03083769|
Recruitment Status : Completed
First Posted : March 20, 2017
Results First Posted : November 20, 2019
Last Update Posted : November 20, 2019
|Condition or disease|
Tacrolimus is an effective immunosuppressive drug widely used in solid organ transplantation to prevent rejection. It is characterized by a narrow therapeutic range and large inter- and intra- individual variability in its pharmacokinetics. Many factors are associated with the variability. Of these factors, genetic factor play an important role. Full understanding of this mechanism is important for the personalized use of tacrolimus and reducing the risk of side effects.The CYP3A5*3 (A6986G) resulting in a splicing defect and the absence of protein activity, was identified as a functional variant (Kuehl P.2001). The CYP3A4*1G was also reported as a functional variant (Richards-Waugh LL. 2014). In addition, other functional variants will also be identified and analyzed in our project.
Our project has two parts:first, retrospective study, 839 renal transplant recipients using tacrolimus as immunosuppressive drug were recruited from Nanfang Hospital. Fifty-eight SNPs from GWAS, GTEx and promoter region of CYP3A gene were genotyped. The association of 58 SNPs on the dose corrected tacrolimus trough levels and side effects (acute rejection, nephrotoxicity and neurotoxicity) were analyzed. Luciferase reporter gene assay were used to identify the functional variants. Second, in this part, there is another renal transplantation cohort. For this cohort, it was a retrospective cohort. All the patients will be stratified to different groups according to the different genotypes. The side effects (acute rejection, nephrotoxicity and neurotoxicity) will be observed.During the study period, all the therapeutic procedures of the patients are as usual.
This will be the largest cohort of this kind of study in Chinese population. The findings will be useful for the patients to improve the therapeutic efficacy and reduce the side effects.
|Study Type :||Observational|
|Actual Enrollment :||1502 participants|
|Actual Study Start Date :||January 1, 1998|
|Actual Primary Completion Date :||July 30, 2019|
|Actual Study Completion Date :||August 1, 2019|
The retrospective cohort consists of about 839 kidney transplant recipients from Nanfang Hospital. These patients used tacrolimus as immunosuppressive drug for preventing the rejection.The side effects (acute rejection, nephrotoxicity and neurotoxicity) will be recorded.
The retrospective cohort consists of about 663 kidney transplant recipients from Guilin No. 924 Hospital. These patients used tacrolimus as immunosuppressive drug for preventing the rejection.The side effects (acute rejection, nephrotoxicity and neurotoxicity) will be recorded.
- Number of Participants With Acute Rejection [ Time Frame: Day 1 to Day 61 ]We will measure the number of participants with acute rejection during the day 1 to day 61 after transplantation. Kaplan-Meier analyses were performed for acute rejection in participants with different genotypes.
- Number of Participants With Tacrolimus-related Nephrotoxicities [ Time Frame: Day1 to Day 61 ]We will measure the number of participants with tacrolimus-related nephrotoxicities during the day 1 to day 61 after transplantation. Kaplan-Meier analyses were performed for tacrolimus-related nephrotoxicities in participants with different genotypes.
- Number of Participants With Tacrolimus-related Neurotoxicities [ Time Frame: Day1 to Day 61 ]We will measure the number of participants with tacrolimus-related neurotoxicities during the day 1 to day 61 after transplantation. Kaplan-Meier analyses were performed for tacrolimus-related neurotoxicities in participants with different genotypes.
Biospecimen Retention: Samples With DNA
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Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03083769
|Guangzhou, Guangdong, China, 510515|
|Guilin No.924 Hospital|
|Guilin, Guangxi, China, 541002|