Functional Genetic Variants Affecting Tacrolimus Trough Levels and Side Effects in Chinese Renal Transplantation.

Transplantation Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03083769
• Other study ID #: NFEC-2016-176
• Status: Completed
• Start date: January 1, 1998
• Est. completion date: August 1, 2019

Study information

• Verified date: October 2019
• Source: Southern Medical University, China
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to determine whether functional genetic variants can affect tacrolimus dose corrected trough levels and associate with the side effects in Chinese renal transplant recipients.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1502
• Est. completion date: August 1, 2019
• Est. primary completion date: July 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Subject has been conducted kidney transplantation. Subject has used tacrolimus as immunosuppressant.

Exclusion Criteria:

Simultaneous liver-kidney transplantation. Patients with age less than 18 years old. Tacrolimus blood concentration monitoring less than 3 times. Failed to extract DNA.

Related Conditions & MeSH terms

• Transplantation

Locations

Country	Name	City	State
China	Nanfang Hospital	Guangzhou	Guangdong
China	Guilin No.924 Hospital	Guilin	Guangxi

Sponsors (3)

Lead Sponsor	Collaborator
Southern Medical University, China	181 Central Hospital of the Chinese PLA, Third Affiliated Hospital, Sun Yat-Sen University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Acute Rejection	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.	Day 1 to Day 61
Primary	Number of Participants With Tacrolimus-related Nephrotoxicities	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.	Day1 to Day 61
Primary	Number of Participants With Tacrolimus-related Neurotoxicities	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.	Day1 to Day 61