Ignite Creation Date:
2025-12-24 @ 10:56 PM
Ignite Modification Date:
2026-02-21 @ 12:30 AM
Study NCT ID:
NCT03083769
Status:
COMPLETED
Last Update Posted:
2019-11-20
First Post:
2017-03-08
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Functional Genetic Variants Affecting Tacrolimus Trough Levels and Side Effects in Chinese Renal Transplantation.
Sponsor:
Organization:
Raw JSON
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These patients used tacrolimus as immunosuppressive drug for preventing the rejection.The side effects (acute rejection, nephrotoxicity and neurotoxicity) will be recorded.', 'otherNumAtRisk': 819, 'deathsNumAtRisk': 819, 'otherNumAffected': 0, 'seriousNumAtRisk': 819, 'deathsNumAffected': 0, 'seriousNumAffected': 256}, {'id': 'EG001', 'title': 'Cohort 2', 'description': '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.', 'otherNumAtRisk': 631, 'deathsNumAtRisk': 631, 'otherNumAffected': 0, 'seriousNumAtRisk': 631, 'deathsNumAffected': 0, 'seriousNumAffected': 37}], 'seriousEvents': [{'term': 'Acute rejection', 'notes': 'Acute rejection for kidney transplant recipients.', 'stats': [{'groupId': 'EG000', 'numAtRisk': 819, 'numEvents': 256, 'numAffected': 256}, {'groupId': 'EG001', 'numAtRisk': 631, 'numEvents': 37, 'numAffected': 37}], 'organSystem': 'Renal and urinary disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Number of Participants With Acute Rejection', 'denoms': [{'units': 'Participants', 'counts': [{'value': '819', 'groupId': 'OG000'}, {'value': '631', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Cohort 1', 'description': '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.'}, {'id': 'OG001', 'title': 'Cohort 2', 'description': '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.'}], 'classes': [{'categories': [{'measurements': [{'value': '256', 'groupId': 'OG000'}, {'value': '37', 'groupId': 'OG001'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Day 1 to Day 61', 'description': '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.', 'unitOfMeasure': 'participants', 'reportingStatus': 'POSTED'}, {'type': 'PRIMARY', 'title': 'Number of Participants With Tacrolimus-related Nephrotoxicities', 'denoms': [{'units': 'Participants', 'counts': [{'value': '819', 'groupId': 'OG000'}, {'value': '631', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Cohort 1', 'description': '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.'}, {'id': 'OG001', 'title': 'Cohort 2', 'description': '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.'}], 'classes': [{'categories': [{'measurements': [{'value': '26', 'groupId': 'OG000'}, {'value': '2', 'groupId': 'OG001'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Day1 to Day 61', 'description': '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.', 'unitOfMeasure': 'participants', 'reportingStatus': 'POSTED'}, {'type': 'PRIMARY', 'title': 'Number of Participants With Tacrolimus-related Neurotoxicities', 'denoms': [{'units': 'Participants', 'counts': [{'value': '819', 'groupId': 'OG000'}, {'value': '631', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Cohort 1', 'description': '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.'}, {'id': 'OG001', 'title': 'Cohort 2', 'description': '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.'}], 'classes': [{'categories': [{'measurements': [{'value': '10', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Day1 to Day 61', 'description': '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.', 'unitOfMeasure': 'participants', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Cohort 1', 'description': '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.'}, {'id': 'FG001', 'title': 'Cohort 2', 'description': '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.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '839'}, {'groupId': 'FG001', 'numSubjects': '663'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '819'}, {'groupId': 'FG001', 'numSubjects': '631'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '20'}, {'groupId': 'FG001', 'numSubjects': '32'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '839', 'groupId': 'BG000'}, {'value': '663', 'groupId': 'BG001'}, {'value': '1502', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Cohort 1', 'description': '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.'}, {'id': 'BG001', 'title': 'Cohort 2', 'description': '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.'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '41.3', 'spread': '11.6', 'groupId': 'BG000'}, {'value': '40.8', 'spread': '10.6', 'groupId': 'BG001'}, {'value': '41.1', 'spread': '11.2', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '263', 'groupId': 'BG000'}, {'value': '189', 'groupId': 'BG001'}, {'value': '452', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '576', 'groupId': 'BG000'}, {'value': '474', 'groupId': 'BG001'}, {'value': '1050', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race (NIH/OMB)', 'classes': [{'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Asian', 'measurements': [{'value': '839', 'groupId': 'BG000'}, {'value': '663', 'groupId': 'BG001'}, {'value': '1502', 'groupId': 'BG002'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Black or African American', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'White', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'More than one race', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'China', 'categories': [{'measurements': [{'value': '839', 'groupId': 'BG000'}, {'value': '663', 'groupId': 'BG001'}, {'value': '1502', 'groupId': 'BG002'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2019-09-23', 'size': 68908, 'label': 'Study Protocol and Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'Prot_SAP_000.pdf', 'typeAbbrev': 'Prot_SAP', 'uploadDate': '2019-09-24T22:12', 'hasProtocol': True}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITH_DNA', 'description': "Human genomic DNA was extracted from leukocytes in patients' peripheral blood."}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'OTHER', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 1502}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '1998-01-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2019-10', 'completionDateStruct': {'date': '2019-08-01', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2019-10-31', 'studyFirstSubmitDate': '2017-03-08', 'resultsFirstSubmitDate': '2019-10-12', 'studyFirstSubmitQcDate': '2017-03-13', 'lastUpdatePostDateStruct': {'date': '2019-11-20', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2019-10-31', 'studyFirstPostDateStruct': {'date': '2017-03-20', 'type': 'ACTUAL'}, 'resultsFirstPostDateStruct': {'date': '2019-11-20', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2019-07-30', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Number of Participants With Acute Rejection', 'timeFrame': 'Day 1 to Day 61', 'description': '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.'}, {'measure': 'Number of Participants With Tacrolimus-related Nephrotoxicities', 'timeFrame': 'Day1 to Day 61', 'description': '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.'}, {'measure': 'Number of Participants With Tacrolimus-related Neurotoxicities', 'timeFrame': 'Day1 to Day 61', 'description': '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.'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['tacrolimus', 'genetic variants', 'side effects'], 'conditions': ['Transplantation']}, 'referencesModule': {'references': [{'pmid': '36927114', 'type': 'DERIVED', 'citation': '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.'}, {'pmid': '35977080', 'type': 'DERIVED', 'citation': 'Yang 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.'}]}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': '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.\n\nOur 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.\n\nThis 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'genderBased': True, 'samplingMethod': 'PROBABILITY_SAMPLE', 'studyPopulation': '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.', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\nSubject has been conducted kidney transplantation. Subject has used tacrolimus as immunosuppressant.\n\nExclusion Criteria:\n\nSimultaneous liver-kidney transplantation. Patients with age less than 18 years old. Tacrolimus blood concentration monitoring less than 3 times. Failed to extract DNA.'}, 'identificationModule': {'nctId': 'NCT03083769', 'briefTitle': 'Functional Genetic Variants Affecting Tacrolimus Trough Levels and Side Effects in Chinese Renal Transplantation.', 'organization': {'class': 'OTHER', 'fullName': 'Southern Medical University, China'}, 'orgStudyIdInfo': {'id': 'NFEC-2016-176'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'Cohort 1', 'description': '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.'}, {'label': 'Cohort 2', 'description': '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.'}]}, 'contactsLocationsModule': {'locations': [{'zip': '510515', 'city': 'Guangzhou', 'state': 'Guangdong', 'country': 'China', 'facility': 'Nanfang Hospital', 'geoPoint': {'lat': 23.11667, 'lon': 113.25}}, {'zip': '541002', 'city': 'Guilin', 'state': 'Guangxi', 'country': 'China', 'facility': 'Guilin No.924 Hospital', 'geoPoint': {'lat': 25.28022, 'lon': 110.29639}}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Southern Medical University, China', 'class': 'OTHER'}, 'collaborators': [{'name': 'Third Affiliated Hospital, Sun Yat-Sen University', 'class': 'OTHER'}, {'name': '181 Central Hospital of the Chinese PLA', 'class': 'OTHER'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'professor', 'investigatorFullName': 'Liang Li', 'investigatorAffiliation': 'Southern Medical University, China'}}}}