Pediatric Liver TransplantNCT06361732
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.
An observational study of Pediatric Liver Transplant, run by Institute of Liver and Biliary Sciences, India at 1 site in India.
Trial summary
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. Read more about this study
- Who is it for?
- Ages Up to 18 years
- Conditions the study is for
- Pediatric Liver Transplant
- How many people
- 80 participants
- Where
- 1 siteIndia
- Study dates
- 17 Dec 2022to 30 Oct 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
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 Up to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: All donors and recipients of Pediatric Liver transplant recipients (0-18 years),from September 2011 till October 2023, follow up atleast 1 for year.
Who may be able to join
- All Pediatric Living donor liver Transpalnt Liver transplant recipients (0-18 years of age) from September 2011 till October 2023 with follow-up at least for 1 year.
Who cannot join
- Incomplete medical records
- Non-availability of Donor to check CYP3A5 polymorphism Deceased donor liver transplantation
- Primary non-function
- Mortality within 2 weeks of liver transplantation Re-transplantation
- Children with Hepatitis C infection
- Multi-visceral or Combined liver-kidney transplantation
- Hepatic artery thrombosis within 6 months of liver transplantation
- Biliary complications within 6 months of liver transplantation requiring intervention
Trial locations and contacts
1 site in 1 country.
India1 site, 1 recruiting
- Recruiting
Institute of Liver and Biliary Sciences
New Delhi, 110070
Dr Snigdha Verma, MD, 01146300000, dr.snigdha1@gmail.com
Dr Rajeev Khanna, MD, 01146300000, drrajeev_khanna@rediffmail.com
About this study
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. Fast
metabolizers 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.
Read the detailed description
Aim: 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.
Primary objective: To compare the 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.
Study population: All donors and recipients of Pediatric Liver transplant recipients (0-18 years),from September 2011 till October 2023, follow up atleast 1 for year.
Study design: Retrospective and Prospective. Intervention: None Monitoring and assessment: Monitoring for the Tac C/D levels, graft functions (AST/ALT) , Toxicities of Tacrolimus(neurological,metabolic) and its correlation to the CYP3A5 and ABCB1 polymorphism. This will be as per standard Institutional protocol followed up since the time of start of transplant program.
Polymorphisms in CYP3A5 and ABCB1: Whole blood samples will be collected for donors and recipients in the EDTA vials. DNA extraction will be done as per the standard procedure followed in
the department. Genotype analysis for CYP3A5 (3/3, 3/1 and 1/1) and ABCB1 3435 (CC, CT \& TT) alleles will be done by polymerase chain reaction (PCR) amplification and will be detected by restriction fragment length polymorphism (RFLP) analysis.
Statistical Analysis: All the categorical variables will be expressed as frequencies, whereas continuous ones will be expressed as mean+ SD or median (IQR). Chi-square , Fisher's exact test and student's t-test will be applied for assessment of causality. Kaplan-Meier statistics will be done for survival and liver related morbidity besides this an appropriate analysis will be carried out at the time of data analysis like diagnostic test, logistic regression etc. Significance will be mentioned in the form of p-value <0.05.
Adverse effects: No such adverse events are involved in the study
- Conditions
- Pediatric Liver Transplant
- Being tested
- No intervention
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No interventionOther
No intervention
| Study group | Role | What they receive |
|---|---|---|
| Liver Transplant | Liver Transplant Receives: Other: No intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 year
Secondary outcomes (9)
Prevalence of CYP3A5 alleles in the donors of pediatric liver transplant recipients.
Measured: Day 0
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.
Measured: Day 0
Prevalence of ABCB1 3435 C/T alleles in the recipients of pediatric liver transplant.
Measured: Day 0
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.
Measured: 1 week, 4 weeks, 3 months & 6 months and 1 year.
Comparison of the Number of Rejection episodes 1 year from LT.
Measured: 1 year
Comparison of proportion of patients who were withdrawn from Mycophenolate or required addition of Mycophenolate 1 year from LT.
Measured: 1 year
Comparison of proportion of patients with renal toxicity 1 year from LT.
Measured: 1 year
Comparison of proportion of patients with Neurological toxicity 1 year from LT.
Measured: 1 year
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.
Measured: 6 months and 1 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2024
- Study start17 Dec 2022
- Primary completion30 Oct 2024 (estimated)
- Study completion30 Oct 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pediatric Liver TransplantStudies of the same condition, open and under way.
- More trials run by Institute of Liver and Biliary Sciences, IndiaThe sponsor's other registered studies.
- 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
- Case only
- Time perspective
- Other
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Institute of Liver and Biliary Sciences, India
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06361732
- Sponsor's protocol ID
- ILBS-liver Transplant-03
- Status last verified
- Apr 2024
- First submitted
- 8 Apr 2024
- Last updated
- 12 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 12 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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.
- ClinicalTrials.gov ID
- NCT06361732
- Acronym / sponsor ID
- ILBS-liver Transplant-03
- Conditions
- Pediatric Liver Transplant
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Institute of Liver and Biliary Sciences, IndiaUniversity, hospital or other
- Study start
- 17 Dec 2022 (actual)
- Primary completion
- 30 Oct 2024 (estimated)
- Study completion
- 30 Oct 2024 (estimated)
- First posted
- 12 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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. Fast
metabolizers 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.
Detailed description
Aim: 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.
Primary objective: To compare the 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.
Study population: All donors and recipients of Pediatric Liver transplant recipients (0-18 years),from September 2011 till October 2023, follow up atleast 1 for year.
Study design: Retrospective and Prospective. Intervention: None Monitoring and assessment: Monitoring for the Tac C/D levels, graft functions (AST/ALT) , Toxicities of Tacrolimus(neurological,metabolic) and its correlation to the CYP3A5 and ABCB1 polymorphism. This will be as per standard Institutional protocol followed up since the time of start of transplant program.
Polymorphisms in CYP3A5 and ABCB1: Whole blood samples will be collected for donors and recipients in the EDTA vials. DNA extraction will be done as per the standard procedure followed in
the department. Genotype analysis for CYP3A5 (3/3, 3/1 and 1/1) and ABCB1 3435 (CC, CT \& TT) alleles will be done by polymerase chain reaction (PCR) amplification and will be detected by restriction fragment length polymorphism (RFLP) analysis.
Statistical Analysis: All the categorical variables will be expressed as frequencies, whereas continuous ones will be expressed as mean+ SD or median (IQR). Chi-square , Fisher's exact test and student's t-test will be applied for assessment of causality. Kaplan-Meier statistics will be done for survival and liver related morbidity besides this an appropriate analysis will be carried out at the time of data analysis like diagnostic test, logistic regression etc. Significance will be mentioned in the form of p-value <0.05.
Adverse effects: No such adverse events are involved in the study
Study design
- Observational model
- Case only
- Time perspective
- Other
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Liver Transplant | – | Other: No interventionLiver Transplant |
Who may qualify
- Ages
- Up to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- All donors and recipients of Pediatric Liver transplant recipients (0-18 years),from September 2011 till October 2023, follow up atleast 1 for year.
Key inclusion criteria (1 listed)
- All Pediatric Living donor liver Transpalnt Liver transplant recipients (0-18 years of age) from September 2011 till October 2023 with follow-up at least for 1 year.
Key exclusion criteria (8 listed)
- Incomplete medical records
- Non-availability of Donor to check CYP3A5 polymorphism Deceased donor liver transplantation
- Primary non-function
- Mortality within 2 weeks of liver transplantation Re-transplantation
- Children with Hepatitis C infection
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| No interventionNo intervention | Other | Liver Transplant |
Primary outcome
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.
Time frame: 1 year
9 secondary outcomes
Prevalence of CYP3A5 alleles in the donors of pediatric liver transplant recipients.
Time frame: Day 0
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.
Time frame: Day 0
Prevalence of ABCB1 3435 C/T alleles in the recipients of pediatric liver transplant.
Time frame: Day 0
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.
Time frame: 1 week, 4 weeks, 3 months & 6 months and 1 year.
Comparison of the Number of Rejection episodes 1 year from LT.
Time frame: 1 year
Comparison of proportion of patients who were withdrawn from Mycophenolate or required addition of Mycophenolate 1 year from LT.
Time frame: 1 year
Comparison of proportion of patients with renal toxicity 1 year from LT.
Time frame: 1 year
Comparison of proportion of patients with Neurological toxicity 1 year from LT.
Time frame: 1 year
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.
Time frame: 6 months and 1 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Apr 2024.
- Individual participant dataSharing planned: Undecided
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Pediatric Liver Transplant, run by Institute of Liver and Biliary Sciences, India at 1 site in India.
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 8 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: status not confirmed, as of the sponsor's last update on 12 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in India. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Dr Snigdha Verma, MD (01146300000, dr.snigdha1@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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. (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 Apr 2024.