Immune ToleranceNCT05501301
Immune Tolerance After Pediatric Liver Transplantation
An observational study of Immune Tolerance and Liver Transplant; Complications, run by RenJi Hospital at 1 site in China.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 1 year to 18 yearsHealthy volunteers can take part
- Conditions the study is for
- Immune Tolerance, Liver Transplant; Complications
- What is being tested?
- IS weaning off
- How many people
- 200 participants
- Where
- 1 siteChina
- Study dates
- 1 Aug 2022to 31 Jul 2025
- 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 1 year to 18 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Study population: The study population is pediatric liver transplantation recipient that received living donor liver transplantation (LDLT) in Ren Ji Hospital affiliated to Shanghai Jiao Tong University School of Medicine. The enrolled recipients should have received LDLT 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. As for most recipient, monotherapy of IS will be applied three months after transplantation, so the enrolled recipients should taking only one type of IS. Since most of pediatric liver transplantation recipients may encounter chronic EBV or CMV infection with one year after transplantation, they may need IS minimization during follow-up. For those patients, IS weaning off will be applied. During the process of IS weaning off, liver function, immunological status and intrahepatic pathology will be closely monitored.
Who may be able to join
- Age at liver transplantation: 4 months to 18 years;
- Original disease before liver transplantation: End-stage liver diseases including cholestatic diseases or metabolic diseases;
- Type of liver transplantation: living donor liver transplantation, with donors of recipient's parents
- Follow-up time after liver transplantation: more than one year
- Liver function: liver function maintains normal and stable 3 months before enrollment
- IS strategy: monotherapy of IS (FK or cyclosporine) or no longer taking any IS
- Liver biopsy: No signs of acute rejection or chronic rejection, and no obvious fibrosis (Ishak<2)
- Written consents are required
Who cannot join
- Original disease before liver transplantation: Tumor, hepatitis virus infection, autoimmune hepatitis, liver failure, secondary liver transplantation
- Type of liver transplantation: ABO incompatible liver transplantation, donors are not recipient's parents or multiple organ transplantation
- Hepatitis virus infection during follow-up
- Severe compilations, including bleeding complication, biliary complication, vessel complication or renal dysfunction -
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Ren Ji Hospital affiliated to Shanghai Jiao Tong University School of Medicine
Shanghai, Shanghai Municipality, 200127
YuN Liu, MD, 86-13651733680, liuyuanbird@163.com
About this study
Official title: Immune Tolerance After Pediatric Liver transplantation-a Cohort Study
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.
Read the detailed description
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
- Immune Tolerance, Liver Transplant; Complications
- Being tested
- IS weaning off
- Keywords
- immune tolerance, pediatric liver transplantation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IS weaning offOther
IS weaning off will be conducted in recipients with chronic virus infection or side effects of IS
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: IS weaning off |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ratio of immune tolerance
The ratio of spontaneous immune tolerance in pediatric liver transplantation recipients, which is free of IS for more than one year with normal liver function
Measured: One year after withdraw of IS
Secondary outcomes (1)
Ratio of acute rejection
The ratio of acute rejection that happens in recipients during the process of IS minimization
Measured: 6 months, 1 year, 2 years and 3 years after enrolled into the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2022
- Study start1 Aug 2022
- Primary completion31 Jul 2025 (estimated)
- Study completion31 Jul 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Immune ToleranceStudies of the same condition, open and under way.
- More trials run by RenJi HospitalThe 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- RenJi Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Liu Yuan, RenJi Hospital
- Investigators
- Qiang Xia, MD, Study director, Ren Ji Hospital affiliated to Shanghai Jiao Tong University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05501301
- Sponsor's protocol ID
- IIT-2022-0004
- Status last verified
- Dec 2023
- First submitted
- 7 Aug 2022
- Last updated
- 19 Dec 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 38833360
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immune Tolerance After Pediatric Liver transplantation-a Cohort Study
- ClinicalTrials.gov ID
- NCT05501301
- Acronym / sponsor ID
- IIT-2022-0004
- Conditions
- Immune Tolerance, Liver Transplant; Complications
- Keywords
- immune tolerance, pediatric liver transplantation
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- RenJi HospitalUniversity, hospital or other
- Study start
- 1 Aug 2022 (actual)
- Primary completion
- 31 Jul 2025 (estimated)
- Study completion
- 31 Jul 2025 (estimated)
- First posted
- 15 Aug 2022 (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.
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
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Immune tolerance cohort | – | Other: IS weaning offPatients 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. |
Who may qualify
- Ages
- 1 year to 18 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
- Study population
- The study population is pediatric liver transplantation recipient that received living donor liver transplantation (LDLT) in Ren Ji Hospital affiliated to Shanghai Jiao Tong University School of Medicine. The enrolled recipients should have received LDLT 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. As for most recipient, monotherapy of IS will be applied three months after transplantation, so the enrolled recipients should taking only one type of IS. Since most of pediatric liver transplantation recipients may encounter chronic EBV or CMV infection with one year after transplantation, they may need IS minimization during follow-up. For those patients, IS weaning off will be applied. During the process of IS weaning off, liver function, immunological status and intrahepatic pathology will be closely monitored.
Key inclusion criteria (8 listed)
- Age at liver transplantation: 4 months to 18 years;
- Original disease before liver transplantation: End-stage liver diseases including cholestatic diseases or metabolic diseases;
- Type of liver transplantation: living donor liver transplantation, with donors of recipient's parents
- Follow-up time after liver transplantation: more than one year
- Liver function: liver function maintains normal and stable 3 months before enrollment
Key exclusion criteria (4 listed)
- Original disease before liver transplantation: Tumor, hepatitis virus infection, autoimmune hepatitis, liver failure, secondary liver transplantation
- Type of liver transplantation: ABO incompatible liver transplantation, donors are not recipient's parents or multiple organ transplantation
- Hepatitis virus infection during follow-up
- Severe compilations, including bleeding complication, biliary complication, vessel complication or renal dysfunction -
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 |
|---|---|---|
| IS weaning offIS weaning off will be conducted in recipients with chronic virus infection or side effects of IS | Other | Immune tolerance cohort |
Primary outcome
Ratio of immune tolerance
Time frame: One year after withdraw of IS
The ratio of spontaneous immune tolerance in pediatric liver transplantation recipients, which is free of IS for more than one year with normal liver function
1 secondary outcome
Ratio of acute rejection
Time frame: 6 months, 1 year, 2 years and 3 years after enrolled into the study
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2023.
- Derived from this study: PubMed 38833360Wang 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.
- Individual participant dataSharing planned: No
Related trials for Immune Tolerance
Active, not recruiting
Effect of Probiotics on Insulin Sensitivity in Overweight and Obese Pregnancy
Obesity & Overweight, Gestational Diabetes Mellitus (GDM)
Not yet recruiting
Evaluating the Effect of the Zeen Mobility Device on Clinical Practicality, Safety, and Impact (Via Assessments of Walking, Standing Tolerance, Balance, Endurance, Effort, and Participation in Daily Tasks) in an Outpatient Rehabilitation Setting for Individuals With Mobility Impairments.
Stroke, Parkinson's Disease (PD)
RecruitingObservational study
Food-i-Sense Analytics: Integrating AI Into Continuous Glucose Monitoring Data Analysis for Precision Nutrition.
Prediabetes (Insulin Resistance, Impaired Glucose Tolerance), Artificial Intelligence Mobile Application
Active, not recruitingPhase 2
Inhaled Treprostinil for Dyspnea and Exercise Intolerance in Mild COPD
COPD (Chronic Obstructive Pulmonary Disease)
Enrolling by invitation
Comparison of the Effects of Oral Hygiene Regimens on Clinical, Immunomodulatory, and Microbial Outcomes and Oral Tolerance in People With Gingivitis
Microbiome, Cytokines
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.
Qiang Xia, MD study director
Ren Ji Hospital affiliated to Shanghai Jiao Tong University School of Medicine
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 Immune Tolerance and Liver Transplant; Complications, run by RenJi Hospital at 1 site in China.
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 8 inclusion and 4 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 19 Dec 2023. 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 China. 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 Yuan Liu, MD (13651733680, liuyuanbird@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ratio of immune tolerance (time frame: One year after withdraw of IS). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05501301, which also lists 1 linked publication.
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 19 Dec 2023.