TransplantationNCT03083769
Functional Genetic Variants Affecting Tacrolimus Trough Levels and Side Effects in Chinese Renal Transplantation.
An observational study of Transplantation, run by Southern Medical University, China at 2 sites in China.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Transplantation
- How many people
- 1,502 participants
- Where
- 2 sitesChina
- Study dates
- 1 Jan 1998to 1 Aug 2019
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- Subject has been conducted kidney transplantation. Subject has used tacrolimus as immunosuppressant.
Who cannot join
- Simultaneous liver-kidney transplantation. Patients with age less than 18 years old. Tacrolimus blood concentration monitoring less than 3 times. Failed to extract DNA.
Trial locations and contacts
2 sites in 1 country.
China2 sites
Nanfang Hospital
Guangzhou, Guangdong, 510515
Guilin No.924 Hospital
Guilin, Guangxi, 541002
About this study
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.
Read the 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.
- Conditions
- Transplantation
- Keywords
- tacrolimus, genetic variants, side effects
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day 1 to Day 61
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.
Measured: Day1 to Day 61
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.
Measured: Day1 to Day 61
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2017
- Study start1 Jan 1998
- Primary completion30 Jul 2019
- Study completion1 Aug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for TransplantationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Other
- Enrolment
- 1,502 participants (actual)
Sponsor and investigators
- Lead sponsor
- Southern Medical University, China
- Sponsor type
- University, hospital or other
- Collaborators
- Third Affiliated Hospital, Sun Yat-Sen University, 181 Central Hospital of the Chinese PLA
- Responsible party
- Principal investigator, Liang Li, Southern Medical University, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03083769
- Sponsor's protocol ID
- NFEC-2016-176
- Status last verified
- Oct 2019
- First submitted
- 8 Mar 2017
- Last updated
- 20 Nov 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Maseko N, Yang S, Li C, Zhang S, Wang R, Zhang Y, Li C, Zhang C, Li L. Impact of genetic polymorphisms on tacrolimus trough blood concentration in Chinese liver transplant recipients. Pharmacogenomics. 2023 Mar;24(4):207-217. doi: 10.2217/pgs-2022-0180. Epub 2023 Mar 17.
PubMed 36927114Yang S, Jiang H, Li C, Lu H, Li C, Ye D, Qi H, Xu W, Bao X, Maseko N, Zhang S, Shao R, Li L. Genomewide association study identifies a novel variant associated with tacrolimus trough concentration in Chinese renal transplant recipients. Clin Transl Sci. 2022 Nov;15(11):2640-2651. doi: 10.1111/cts.13388. Epub 2022 Aug 28.
PubMed 35977080
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Functional Genetic Variants Affecting Tacrolimus Trough Levels and Side Effects in Chinese Renal Transplantation.
- ClinicalTrials.gov ID
- NCT03083769
- Acronym / sponsor ID
- NFEC-2016-176
- Conditions
- Transplantation
- Keywords
- tacrolimus, genetic variants, side effects
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 1,502 participants (actual)
- Lead sponsor
- Southern Medical University, ChinaUniversity, hospital or other
- Collaborators
- Third Affiliated Hospital, Sun Yat-Sen University, 181 Central Hospital of the Chinese PLA
- Study start
- 1 Jan 1998 (actual)
- Primary completion
- 30 Jul 2019 (actual)
- Study completion
- 1 Aug 2019 (actual)
- First posted
- 20 Mar 2017 (actual)
- Results
- Posted 20 Nov 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Other
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (1 listed)
- Subject has been conducted kidney transplantation. Subject has used tacrolimus as immunosuppressant.
Key exclusion criteria (1 listed)
- Simultaneous liver-kidney transplantation. Patients with age less than 18 years old. Tacrolimus blood concentration monitoring less than 3 times. Failed to extract DNA.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36927114Maseko N, Yang S, Li C, Zhang S, Wang R, Zhang Y, Li C, Zhang C, Li L. Impact of genetic polymorphisms on tacrolimus trough blood concentration in Chinese liver transplant recipients. Pharmacogenomics. 2023 Mar;24(4):207-217. doi: 10.2217/pgs-2022-0180. Epub 2023 Mar 17.
- Derived from this study: PubMed 35977080Yang S, Jiang H, Li C, Lu H, Li C, Ye D, Qi H, Xu W, Bao X, Maseko N, Zhang S, Shao R, Li L. Genomewide association study identifies a novel variant associated with tacrolimus trough concentration in Chinese renal transplant recipients. Clin Transl Sci. 2022 Nov;15(11):2640-2651. doi: 10.1111/cts.13388. Epub 2022 Aug 28.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Transplantation, run by Southern Medical University, China at 2 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Nov 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Acute Rejection (time frame: Day 1 to Day 61). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03083769, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Nov 2019.