protocolSection identificationModule nctId: NCT06361732, orgStudyIdInfo id: ILBS-liver Transplant-03, briefTitle: Prevalence of CYP3A5 Polymorphisms in the Donors and ABCB1 Polymorphisms in the Recipients Undergoing Pediatric Liver Transplant and Their Influence on Tacrolimus Levels and Graft Function., statusModule overallStatus: RECRUITING, startDateStruct date: 2022-12-17, primaryCompletionDateStruct date: 2024-10-30, completionDateStruct date: 2024-10-30, studyFirstPostDateStruct date: 2024-04-12, lastUpdatePostDateStruct date: 2024-04-12, sponsorCollaboratorsModule leadSponsor name: Institute of Liver and Biliary Sciences, India, class: OTHER, descriptionModule briefSummary: It is known that Immunosuppression post-Liver transplant is central to achieving optimal outcomes in liver transplant recipients. It is required to maintain an adequate balance between reducing rejection and toxicities. Mainstay drugs for maintenance therapy are Calcinuerin inhibitors - Tacrolimus versus cyclosporine. Tacrolimus is preferred, as it has less rejection and better graft survival. However, there is risk of renal and metabolic toxicities. Tacrolimus is bound mainly to alpha1-acid-glycoprotein (encoded by the ABCB1gene) expressed on various epithelial and endothelial cells and lymphocytes. Elimination occurs by metabolizing enzymes of cytochrome P450 system, with biliary excretion (95%) of metabolites (majority) with minority through urine (2.4%). Demethylation and hydroxylation of tacrolimus occurs by hepatic and intestinal CYP3A isoforms (CYP3A4 and CYP3A5). Among the factors that play an important role in the pharmacokinetics of tacrolimus, thus affecting the tacrolimus trough levels in the body and in turn influencing the dosing of the drug required to maintain an adequate balance between reducing rejection and toxicities, genetics plays an important role. Increased expression of CYP3A5 causes more metabolism of tacrolimus and hence affecting the tacrolimus concentration/weight-adjusted dose (C/W-D) ratio in the body. The wild type (CYP3A5\*3) are slow metabolizers and mutant ones (CYP3A5 \*1/\*1 and CYP3A5 \*1/\*3) are fast metabolizers. Fastmetabolizers have a low C/W-D ratio and require higher Tacrolimus dosing and are thus susceptible to renal and metabolic toxicities, EBV viremia and post transplant lymphoproliferative disorder. Polymorphisms in ABCB1 (c.3435C\>T) are also known to influence tacrolimus dosage in the first week of transplant (C/D ratio was lower in ABCB1 3435CC in comparison to CT and TT). There is no such data in pediatric liver transplant setting from Indian subcontinent. The aim of the study is to study the prevalence of CYP3A5 polymorphisms in the donors and ABCB1 polymorphisms in the recipients undergoing Paediatric liver transplant and their influence on Tacrolimus levels and graft function., conditionsModule conditions: Pediatric Liver Transplant, designModule studyType: OBSERVATIONAL, designInfo observationalModel: CASE_ONLY, timePerspective: OTHER, enrollmentInfo count: 80, type: ESTIMATED, armsInterventionsModule interventions name: No intervention, outcomesModule primaryOutcomes measure: Time (in days) to achieve transaminases within 1.5 times ULN (60 IU/L) in the pediatric Liver transplant recipients with grafts from slow metabolizer (CYP3A5*3/3 allele) versus fast metabolizer (CYP3A5*1/3 and 1/1 alleles) donors., secondaryOutcomes measure: Prevalence of CYP3A5 alleles in the donors of pediatric liver transplant recipients., secondaryOutcomes measure: Influence of donor CYP3A5 alleles (slow versus fast metabolizers) on tacrolimus concentration-weight adjusted dose ratio at 1 week, 4 weeks, 3 months & 6 months and 1 year after liver transplantation., secondaryOutcomes measure: Prevalence of ABCB1 3435 C/T alleles in the recipients of pediatric liver transplant., secondaryOutcomes measure: Influence of recipient ABCB1 3435 C/T on tacrolimus concentration-weight adjusted dose ratio at 1 week, 4 weeks, 3 months and 6 months and 1 year after liver transplantation., secondaryOutcomes measure: Comparison of the Number of Rejection episodes 1 year from LT., secondaryOutcomes measure: Comparison of proportion of patients who were withdrawn from Mycophenolate or required addition of Mycophenolate 1 year from LT., secondaryOutcomes measure: Comparison of proportion of patients with renal toxicity 1 year from LT., secondaryOutcomes measure: Comparison of proportion of patients with Neurological toxicity 1 year from LT., secondaryOutcomes measure: Comparison of e-GFRand cystatin-C levels in the two cohorts of pediatric liver transplant recipients with grafts from slow metabolizer (CYP3A5*3/3 allele) versus fast metabolizer (CYP3A5*1/3 and 1/1 alleles) donors., eligibilityModule sex: ALL, maximumAge: 18 Years, stdAges: CHILD, stdAges: ADULT, contactsLocationsModule locations facility: Institute of Liver and Biliary Sciences, status: RECRUITING, city: New Delhi, zip: 110070, country: India, contacts name: Dr Snigdha Verma, MD, role: CONTACT, phone: 01146300000, email: dr.snigdha1@gmail.com, contacts name: Dr Rajeev Khanna, MD, role: CONTACT, phone: 01146300000, email: drrajeev_khanna@rediffmail.com, geoPoint lat: 28.63576, lon: 77.22445, hasResults: False