Efficacy and Safety of Immunosuppressive Withdrawal After Pediatric Liver Transplantation

November 23, 2023 updated by: Wei Gao

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

47

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Tianjin
      • Tianjin, Tianjin, China, 300192
        • Tianjin First Central Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: immunosuppressive withdrawal
After enrollment,the recipients will take IS withdrawal follow the protocol of this study.Following enrollment, recipients will be examined at several time periods such as peripheral blood test,liver function , liver biopsy, and other relevant indicators to determine immunosuppressant withdrawal condition and adverse effects.
Drug: Tacrolimus or Cyclosporine A
The protocol of IS withdrawal:Week 1-4 take Tacrolimus (Tac) or Cyclosporine A (CsA) once daily for weeks. Week 5-8 medication reduction to taking Tac / CsA 4 times a week . Week 9-12 reduction to taking Tac/ CsA 3 times a week. Week 13-18 reduction to taking Tac / CsA 2 times a week . Week 19-24 reduction to taking Tac/ CsA once per week. Week 25, the recipients will stop taking Tac/ CsA.
Other Names:
  • immunosuppression withdrawal

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of immune tolerance participants
Time Frame: Enrollment to 2 year post cessation of immunosuppression
Number of participants who are immune tolerance, defined as those who successfully withdraw from immunosuppression and maintain normal graft status as assessed by liver biopsy and liver tests 2 years after complete immunosuppression withdrawal.
Enrollment to 2 year post cessation of immunosuppression

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with complications attributed to immunosuppression withdrawal
Time Frame: Enrollment to 4 year post cessation of immunosuppression
This endpoint is comprised of complications related to immunosuppression withdrawal and is defined as the occurrence of any of the following: death or graft loss, histologic evidence of refractory acute rejection or biopsy confirmed chronic rejection.
Enrollment to 4 year post cessation of immunosuppression
Impact of iImmunosuppression withdrawal on graft histology
Time Frame: Enrollment to 4 year post cessation of immunosuppression
Histologic progression determined from the stage of fibrosis at baseline to completion of the study according to the Ishak Severity System
Enrollment to 4 year post cessation of immunosuppression
Severity of acute rejection in immunotolerant recipients
Time Frame: Enrollment to 2 year post cessation of immunosuppression
Acute rejection severity (mild, moderate, severe) is based on the Banff global assessment grade according to the central pathology reading of the liver biopsy.
Enrollment to 2 year post cessation of immunosuppression

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Wei Gao

Investigators

  • Principal Investigator: Wei Gao, MD, Tianjin First Central Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

December 1, 2023

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

December 1, 2028

Study Registration Dates

First Submitted

October 26, 2023

First Submitted That Met QC Criteria

November 23, 2023

First Posted (Actual)

November 27, 2023

Study Record Updates

Last Update Posted (Actual)

November 27, 2023

Last Update Submitted That Met QC Criteria

November 23, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2023DZX32

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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