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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03083769
Recruitment Status : Completed
First Posted : March 20, 2017
Results First Posted : November 20, 2019
Last Update Posted : November 20, 2019
Sponsor:
Collaborators:
Third Affiliated Hospital, Sun Yat-Sen University
181 Central Hospital of the Chinese PLA
Information provided by (Responsible Party):
Liang Li, Southern Medical University, China

Tracking Information
First Submitted Date March 8, 2017
First Posted Date March 20, 2017
Results First Submitted Date October 12, 2019
Results First Posted Date November 20, 2019
Last Update Posted Date November 20, 2019
Actual Study Start Date January 1, 1998
Actual Primary Completion Date July 30, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: October 31, 2019)
  • 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.
Original Primary Outcome Measures
 (submitted: March 13, 2017)
  • Kidney transplant recipient genotypes [ Time Frame: Day 0 to Day 30 ]
    time to acute rejection
  • Kidney transplant recipient genotypes [ Time Frame: Day 0 to Day 30 ]
    time to Calcineurin Inhibitor (CNI)-related nephrotoxicities
  • Kidney transplant recipient genotypes [ Time Frame: Day 0 to Day 30 ]
    time to Calcineurin Inhibitor (CNI)-related neurotoxicities
  • Liver transplant recipient genotypes [ Time Frame: Day 0 to Day 30 ]
    time to acute rejection
  • Liver transplant recipient genotypes [ Time Frame: Day 0 to Day 30 ]
    time to Calcineurin Inhibitor (CNI)-related nephrotoxicities
  • Liver transplant recipient genotypes [ Time Frame: Day 0 to Day 30 ]
    time to Calcineurin Inhibitor (CNI)-related neurotoxicities
  • Liver donor genotypes [ Time Frame: Day 0 to Day 30 ]
    time to acute rejection
  • Liver donor genotypes [ Time Frame: Day 0 to Day 30 ]
    time to Calcineurin Inhibitor (CNI)-related nephrotoxicities
  • Liver donor genotypes [ Time Frame: Day 0 to Day 30 ]
    time to Calcineurin Inhibitor (CNI)-related neurotoxicities
Change History
Current Secondary Outcome Measures Not Provided
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Functional Genetic Variants Affecting Tacrolimus Trough Levels and Side Effects in Chinese Renal Transplantation.
Official Title Not Provided
Brief 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.
Detailed 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.

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Other
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Human genomic DNA was extracted from leukocytes in patients' peripheral blood.
Sampling Method Probability Sample
Study Population The study population consists of the renal transplant recipients who received tacrolimus as immunosuppressant from Nanfang Hospital and Guilin No.924 Hospital. All the patients are Chinese.
Condition Transplantation
Intervention Not Provided
Study Groups/Cohorts
  • 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.
  • 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.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: October 31, 2019)
1502
Original Estimated Enrollment
 (submitted: March 13, 2017)
1500
Actual Study Completion Date August 1, 2019
Actual Primary Completion Date July 30, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria

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.

Sex/Gender
Sexes Eligible for Study: All
Gender Based Eligibility: Yes
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries China
Removed Location Countries  
 
Administrative Information
NCT Number NCT03083769
Other Study ID Numbers NFEC-2016-176
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party Liang Li, Southern Medical University, China
Study Sponsor Southern Medical University, China
Collaborators
  • Third Affiliated Hospital, Sun Yat-Sen University
  • 181 Central Hospital of the Chinese PLA
Investigators Not Provided
PRS Account Southern Medical University, China
Verification Date October 2019