Clinical trial NCT06147375: Efficacy and Safety of Immunosuppressive Withdrawal After Pediatric Liver Transplantation
Official title: Efficacy and Safety of Immunosuppressive Withdrawal After Pediatric Liver Transplantation
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Immune Tolerance
Immunosuppression
Liver Transplant; Complications
Keywords: Immune Tolerance
Pediatric liver transplant
Immunosuppression
Lead sponsor: Tianjin First Central Hospital
Sponsor class: OTHER
First posted: 2023-11-27
Enrollment: 47
Sex: ALL
Minimum age (years): 4
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: The goal of this clinical trial is to learn about the efficacy and safety of immunosuppressive withdrawal in pediatric liver transplant recipients. The main question it aims to answer is:exploring the landscape of immune tolerance after pediatric liver transplantation. Moreover,this clinical trial aims to provide important foundation and clinical data for inducing immune tolerance, as well as to clarify the mechanism of immune tolerance development in pediatric liver transplantation, identify biomarkers that can be used to predict immune tolerance, and build a prediction model of immune tolerance after pediatric liver transplantation.

The study planned to enroll 47 recipients after pediatric liver transplantation which would gradually withdrawal immunosuppressive after enrollment, divided the participants into immune tolerance and immune intolerance groups based on the outcome of immunosuppressive withdrawal.In this study, we collect the peripheral blood and liver biopsy samples from the two groups, find biomarkers with predictive value for immune tolerance in recipients after pediatric liver transplantation, and build a predictive model of immune tolerance by machine learning.

Detailed description: Background: The main conditions which require pediatric liver transplantation are benign diseases with curable primary diseases, such as metabolic and biliary diseases. After liver transplantation, the two main risk factors affecting recipients survival are cumulative IS toxicity and chronic graft injuries. Adverse reactions such as renal dysfunction, metabolic problems, infection, and cancer can result from chronic exposure to IS. As a result, decreasing or stopping immunosuppressive treatment is an effective way for improving recipients survival after liver transplantation. Currently, the recipients after pediatric liver transplantation lacks defined IS withdrawal plans and also unified and uniform recipients selection criteria and processes. Additionally, IS withdrawal could result in graft fibrosis, rejection, and graft dysfunction.Therefore, the safety and efficacy of IS withdrawal needs to be discussed.

Methods:The study planned to enroll 47 recipients after pediatric liver transplantation which would gradually withdrawal IS after enrollment, divided the participants into immune tolerance and immune intolerance groups based on the outcome of IS withdrawal.In this study, we will collect the peripheral blood and liver biopsy samples from the two groups, find biomarkers with predictive value for immune tolerance in recipients after pediatric liver transplantation, and build a predictive model of immune tolerance by machine learning.

Protocol after enrollment: After enrollment,the recipients will take IS withdrawal follow the protocol of this study.The IS withdrawal protocol is once daily for weeks 1 to 4, then decreased every 4 weeks until the IS is totally stopped by 25 weeks. Following enrollment, recipients will be examined at several time periods such as peripheral blood tests,liver function , liver biopsy, and other relevant indicators to determine IS withdrawal and adverse effects.

Eligibility criteria: Inclusion Criteria:

* Age at liver transplantation: under 6 years
* Follow-up time after liver transplantation: more than 4 years
* Liver function maintains normal before enrollment
* Monotherapy of IS (Tacrolimus or Cyclosporine A)
* Liver biopsy: No signs of acute rejection or chronic rejection, and no obvious fibrosis (Ishak\<2) 2 years before enrollment
* Female recipients of fertility treatment must have a negative pregnancy test before enrollment
* No Hepatitis virus infection 1 year before enrollment
* Written consents are required

Exclusion Criteria:

* Original disease before liver transplantation: Tumor, secondary liver transplantation, hepatitis virus infection, autoimmune hepatitis
* Type of liver transplantation: ABO incompatible liver transplantation or multiple organ transplantation
* Liver biopsy: obvious fibrosis(Ishak≥2；LAFSc moderate or severe)
* Recipients taking IS for other diseases besides their liver transplantation

Primary outcomes:
measure: Number of immune tolerance participants
timeFrame: Enrollment to 2 year post cessation of immunosuppression
Secondary outcomes:
measure: Number of participants with complications attributed to immunosuppression withdrawal
timeFrame: Enrollment to 4 year post cessation of immunosuppression
measure: Impact of iImmunosuppression withdrawal on graft histology
timeFrame: Enrollment to 4 year post cessation of immunosuppression
measure: Severity of acute rejection in immunotolerant recipients
timeFrame: Enrollment to 2 year post cessation of immunosuppression
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Tianjin First Central Hospital
state: Tianjin
Study officials:
affiliation: Tianjin First Central Hospital
name: Wei Gao, MD
role: PRINCIPAL_INVESTIGATOR
References: