Immune ToleranceNCT06147375
Efficacy and Safety of Immunosuppressive Withdrawal After Pediatric Liver Transplantation
A study testing Tacrolimus or Cyclosporine A in people with Immune Tolerance and Immunosuppression, run by Wei Gao at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 4 years and older
- Conditions the study is for
- Immune Tolerance, Immunosuppression, Liver Transplant; Complications
- What is being tested?
- Tacrolimus or Cyclosporine A
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 47 participants
- Where
- 1 siteChina
- Study dates
- 1 Dec 2023to Dec 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 4 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Tianjin First Central Hospital
Tianjin, Tianjin Municipality, 300192
Wei Gao, MD, 0086-13920128996, gaowei_tjfch@163.com
About this study
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.
Read the 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.
- Being tested
- Tacrolimus or Cyclosporine A
- Keywords
- Immune Tolerance, Pediatric liver transplant, Immunosuppression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tacrolimus or Cyclosporine ADrug
Also called immunosuppression withdrawal
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.
| Study group | Role | What they receive |
|---|---|---|
| immunosuppressive withdrawal | Experimental | 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. Receives: Drug: Tacrolimus or Cyclosporine A |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of immune tolerance participants
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.
Measured: Enrollment to 2 year post cessation of immunosuppression
Secondary outcomes (3)
Number of participants with complications attributed to immunosuppression withdrawal
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.
Measured: Enrollment to 4 year post cessation of immunosuppression
Impact of iImmunosuppression withdrawal on graft histology
Histologic progression determined from the stage of fibrosis at baseline to completion of the study according to the Ishak Severity System
Measured: Enrollment to 4 year post cessation of immunosuppression
Severity of acute rejection in immunotolerant recipients
Acute rejection severity (mild, moderate, severe) is based on the Banff global assessment grade according to the central pathology reading of the liver biopsy.
Measured: Enrollment to 2 year post cessation of immunosuppression
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Nov 2023
- Study start1 Dec 2023 (estimated)
- Primary completionDec 2026 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Immune ToleranceStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 47 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Wei Gao
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Wei Gao, Tianjin First Central Hospital
- Investigators
- Wei Gao, MD, Principal investigator, Tianjin First Central Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06147375
- Sponsor's protocol ID
- 2023DZX32
- Status last verified
- Nov 2023
- First submitted
- 26 Oct 2023
- Last updated
- 27 Nov 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Immunosuppressive Withdrawal After Pediatric Liver Transplantation
- ClinicalTrials.gov ID
- NCT06147375
- Acronym / sponsor ID
- 2023DZX32
- Keywords
- Immune Tolerance, Pediatric liver transplant, Immunosuppression
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 47 participants (estimated)
- Lead sponsor
- Wei GaoUniversity, hospital or other
- Study start
- 1 Dec 2023 (estimated)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 27 Nov 2023 (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.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| immunosuppressive withdrawal | Experimental | Drug: Tacrolimus or Cyclosporine AAfter 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. |
Who may qualify
- Ages
- 4 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (4 listed)
- 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
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 |
|---|---|---|
| Tacrolimus or Cyclosporine AAlso: immunosuppression withdrawalThe 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. | Drug | immunosuppressive withdrawal |
Primary outcome
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.
3 secondary outcomes
Number of participants with complications attributed to immunosuppression withdrawal
Time frame: 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
Severity of acute rejection in immunotolerant recipients
Time frame: Enrollment to 2 year post cessation of immunosuppression
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Nov 2023.
- Individual participant dataSharing planned: No
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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.
Wei Gao, MD principal investigator
Tianjin First Central Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Tacrolimus or Cyclosporine A in people with Immune Tolerance and Immunosuppression, run by Wei Gao 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: opening soon, as of the sponsor's last update on 27 Nov 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Wei Gao, MD (0086-13920128996, gaowei_tjfch@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of immune tolerance participants (time frame: Enrollment to 2 year post cessation of immunosuppression). 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 27 Nov 2023.