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

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Total Enrollment

1502 participants

Study Classification

OBSERVATIONAL

Study Start Date

1998-01-01

Study Completion Date

2019-08-01

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Retrospective Study of Long-term Survival and Related Factors Among Kidney Transplant Recipients in China

NCT01796639

Kidney Transplantation

COMPLETED

Validation of Gene Expression Markers of Renal Allograft Functional Decline

NCT01782586

Kidney Transplant Recipients

COMPLETED

Measurement of Patient Reported Outcomes in Renal Transplant Patients With And Without Gastrointestinal (GI) Symptoms

NCT01300416

Kidney Transplantation GI Symptoms Severity

COMPLETED

Immunosuppressive Regimen on Changes in Renal Function and Transplant Rejection Rate in Patients With Lung Transplant

NCT03657004

Lung Transplant; Complications Chronic Kidney Diseases

COMPLETED

Genomics of Kidney Transplantation

NCT01714440

KidneyTransplant Recipients Simultaneous Kidney/Pancreas Recipients Kidney Transplant Donor

COMPLETED

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Transplantation

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Observational Model Type

COHORT

Study Time Perspective

OTHER

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Cohort 1

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.

No interventions assigned to this group

Cohort 2

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.

No interventions assigned to this group

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No