MedDataX Logo

Immune Tolerance After Pediatric Liver Transplantation

NCT ID: NCT05501301

Last Updated: 2023-12-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Total Enrollment

200 participants

Study Classification

OBSERVATIONAL

Study Start Date

2022-08-01

Study Completion Date

2025-07-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Immunosuppressive (IS) agents are effective treatment to avoid acute or chronic rejection after pediatric liver transplantation. However, long-term side effect of IS intaking, like infection, kidney dysfunction, metabolic disorders and developmental retardation, should be aware, especially in pediatric recipients. Spontaneous immune tolerance is defined as recipients who cease to taking IS agents due to multiple reasons and the liver function maintained normal. However, the real ratio and safety of immune tolerance in pediatric liver transplantation recipients are rarely known. We would like to investigate the ratio and safety of spontaneous immune tolerance in pediatric liver transplantation recipients during long-term follow-up by constructing an immune tolerance cohort. In this cohort, long-term pediatric liver transplantation recipients with normal liver function and taking monotherapy of IS would be involved. The IS strategy would be monitored and adjusted according to the "Clinical guidelines for pediatric liver transplantation in China(2015)". For recipients suffering refractory virus infection, such as EBV or CMV infection, IS will be minimized to assist the clearance of virus until IS was weaned off. Since most of pediatric liver transplantation recipients may encounter chronic EBV or CMV infection within one year after transplantation, they may need IS minimization during follow-up. During the process of IS weaning off, liver function, immunological status and intrahepatic pathology will be closely monitored. If acute rejection or other complications were found, increase of IS dosage or other related treatments will be applied. Immune tolerance is defined as liver function and intrahepatic pathology maintain normal for more than one year after stop taking IS. At the end of study, the ratio of immune tolerance, acute rejection and all types of complications will be assessed.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Background: Immune tolerance after liver transplantation is defined as the status that recipients no longer taking any immunosuppressive agents with normal liver function and intrahepatic pathology. For pediatric liver transplantation recipients, immune tolerance is easier to reach than adult liver transplantation recipients. It is reported that spontaneous immune tolerance ratio in pediatric liver transplantation recipients is between 15%-60%, varying among different centers. Some recipients could develop into spontaneous immune tolerance due to refractory infections or side effects of IS. Some recipients could also reach immune tolerance by gradually weaning off the IS if liver function maintained normal and stable in the long-term follow-up. What's more, immune tolerance could reduce the long-term side effects of IS in pediatric recipients. However, how the immune status was modulated, or which factors contribute to the development of immune tolerance is unknown. Besides, the long-term safety of immune tolerance also needs more research. This study is designed to figure out the ratio and safety of immune tolerance in pediatric liver transplantation recipients.

Assessment before enrollment: In this study, enrolled population should have received living donor liver transplantation (LDLT) in Ren Ji Hospital affiliated to Shanghai Jiao Tong University School of Medicine for more than one year and liver function maintains stable and normal for more than 3 months. No severe complication including vessel complications, biliary complications or renal dysfunction should occur before enrollment. Liver biopsy should indicate no signs of acute rejection or chronic rejection, and no obvious fibrosis (Ishak\<2).

Protocol after enrollment: After enrollment, the recipients will be evaluated for virus infection and side effects of IS. For patients with refractory EBV or CMV infections, or obvious side effects of IS, IS minimization should be applied. The dosage of IS will be weaned off as the 3/4 dosage of last dosage every 4 weeks. During the process of weaning off, liver function will be monitored every two weeks and liver biopsy should be conducted every six months. If liver dysfunction or acute rejection is detected during follow-up, steroid bolus and increased IS will be applied. For patients who have stop taking any IS, liver biopsy will be conducted to exclude potential liver injury in liver biopsy. For patients who have stop taking IS for more than one year with normal liver function and liver pathology, immune tolerance is considered as reached. At the endpoint of study, the ratio of immune tolerance, ratio of acute rejection and safety of immune tolerance will be assessed.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Immune Tolerance Liver Transplant; Complications

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

immune tolerance, pediatric liver transplantation

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Immune tolerance cohort

Patients that are enrolled into this cohort will receive IS minimization if virus infection or side effects of IS was found. The strategy of IS minimization will follow the "Clinical guidelines for pediatric liver transplantation in China(2015)". Blood test and liver biopsy will be conducted to monitor liver function and intrahepatic pathological conditions. If IS is ceased for more than one year without liver dysfunction or signs of acute rejection in liver biopsy, immune tolerance was considered reached.

IS weaning off

Intervention Type OTHER

IS weaning off will be conducted in recipients with chronic virus infection or side effects of IS

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

IS weaning off

IS weaning off will be conducted in recipients with chronic virus infection or side effects of IS

Intervention Type OTHER

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Age at liver transplantation: 4 months to 18 years;
2. Original disease before liver transplantation: End-stage liver diseases including cholestatic diseases or metabolic diseases;
3. Type of liver transplantation: living donor liver transplantation, with donors of recipient's parents
4. Follow-up time after liver transplantation: more than one year
5. Liver function: liver function maintains normal and stable 3 months before enrollment
6. IS strategy: monotherapy of IS (FK or cyclosporine) or no longer taking any IS
7. Liver biopsy: No signs of acute rejection or chronic rejection, and no obvious fibrosis (Ishak\<2)
8. Written consents are required

Exclusion Criteria

1. Original disease before liver transplantation: Tumor, hepatitis virus infection, autoimmune hepatitis, liver failure, secondary liver transplantation
2. Type of liver transplantation: ABO incompatible liver transplantation, donors are not recipient's parents or multiple organ transplantation
3. Hepatitis virus infection during follow-up
4. Severe compilations, including bleeding complication, biliary complication, vessel complication or renal dysfunction -
Minimum Eligible Age

1 Year

Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

RenJi Hospital

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Liu Yuan

Assistant professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Qiang Xia, MD

Role: STUDY_DIRECTOR

Ren Ji Hospital affiliated to Shanghai Jiao Tong University School of Medicine

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Ren Ji Hospital affiliated to Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, China

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

China

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Yuan Liu, MD

Role: CONTACT

Phone: 13651733680

Email: [email protected]

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

YuN Liu, MD

Role: primary

References

Explore related publications, articles, or registry entries linked to this study.

Wang B, Zhou A, Wu Y, Pan Q, Wei X, Gao Y, Xiao W, Jin J, Zhou T, Luo Y, Zhan Z, Liu Y, Gao W, Liu Y, Xia Q. Establishment and validation of a predictive model of immune tolerance after pediatric liver transplantation: a multicenter cohort study. Int J Surg. 2024 Sep 1;110(9):5615-5626. doi: 10.1097/JS9.0000000000001671.

Reference Type DERIVED
PMID: 38833360 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

IIT-2022-0004

Identifier Type: -

Identifier Source: org_study_id