Immunosuppression Withdrawal for Pediatric Living-donor Liver Transplant Recipients (ITN029ST)
Overview
- Phase
- Phase 1
- Intervention
- Immunosuppression Withdrawal
- Conditions
- Liver Transplant
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Enrollment
- 20
- Locations
- 3
- Primary Endpoint
- Proportion of Participants Successfully Withdrawn From Immunosuppression
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief Summary
Antirejection medicines, also known as immunosuppressive drugs, are prescribed to organ transplant recipients to prevent their bodies from rejecting the new organ. Long-term use of these drugs places transplant recipients at higher risk of serious infections and certain types of cancer. The purpose of this study is to determine whether immunosuppressive drugs can be safely withdrawn over a minimum of 9 months from children who received liver transplants at least 4 years ago.
Detailed Description
In order to prevent the rejection of transplanted organs, transplant recipients are prescribed a strict, lifelong regimen of immunosuppressive drugs. While these drugs help prevent the body from rejecting the transplant, they carry numerous complications, including increased risk of serious infections and certain types of cancer. However, there is mounting evidence that a significant percentage of liver transplant recipients can maintain a healthy, functioning transplant without ongoing immunosuppression. This study will determine whether gradual withdrawal and eventual discontinuation of all immunosuppressive medication can be safely accomplished in children who received a liver transplant from a parent. Twenty eligible participants who were under 18 years old at the time of transplant, whose donor was a parent, and who received the transplant at least four years ago will be enrolled in the study. Liver recipients will have an initial screening assessment consisting of a medical history, liver biopsy, and urine and blood collection. Eligible recipients will be placed on a modified medication schedule to gradually decrease their immunosuppression medication slowly over a 9- to 12-month period, during which time they will be closely monitored by study staff. Immunosuppressive drugs will not be provided by this study. For a minimum of 3 and up to a maximum of 7 years, monthly telephone consultations and quarterly study visits will occur. Visits will include physical exams and blood collection to monitor the children's health during the withdrawal phase. The exact schedule of immunosuppressant withdrawal will be determined by study physicians based on participant's health and immune function test results. Donor and nondonor parents will be asked to each provide one blood sample during the initial study visits for immunologic and genetic testing. \*\*\* IMPORTANT NOTICE: \*\*\* The National Institute of Allergy and Infectious Diseases and the Immune Tolerance Network do not recommend the discontinuation of immunosuppressive therapy for recipients of cell, organ, or tissue transplants outside of physician-directed, controlled clinical studies. Discontinuation of prescribed immunosuppressive therapy can result in serious health consequences and should only be performed in certain rare circumstances, upon the recommendation and with the guidance of your health care provider.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Immunosuppression Withdrawal
Recipients of parental living donor liver transplants 4 or more years prior to trial enrollment, who also had stable allograft function during the preceding 6 months while taking a single immunosuppressive drug were permitted to undergo withdrawal of immunosuppression therapy. With high dose, daily dose reduction by 25% for 8 weeks. With low dose, daily dose reduction by 25% for 4 weeks. Participants are carefully evaluated/monitored throughout the study by assessments including but not limited to liver biopsy, liver tests and clinic visits, alloantibodies, autoantibodies and quantitative immunoglobulin G test results.
Intervention: Immunosuppression Withdrawal
Outcomes
Primary Outcomes
Proportion of Participants Successfully Withdrawn From Immunosuppression
Time Frame: 1 year after completion of immunosuppression withdrawal
Participants were considered successfully withdrawn from immunosuppression if they remained off immunosuppression for at least one year with normal allograft function.
Secondary Outcomes
- Number of Participants Who Suffered Graft Loss or Died Following Initiation of Immunosuppression Withdrawal(Enrollment through end of study (up to 9.5 years))
- Time From Start of Immunosuppression Withdrawal to the First Episode of Acute Rejection, Second Episode of Rejection That Did Not Require Treatment, or to Diagnosis of Chronic Rejection(From the start of immunosuppression withdrawal to first acute rejection, second episode of rejection that did not require treatment, or diagnosis of chronic rejection through end of study (up to 9.5 years))
- Immunosuppression-Free Duration(Completion of Withdrawal to either end of trial participation (up to 9.5 years) or time to restarting immunosuppression)
- Distribution of Histologic Severity Among Rejection Episodes(Start of immunosuppressive withdrawal to rejection through end of study (up to 9.5 years))
- Number of Participants Experiencing Adverse Events by Severity(Enrollment through end of study (up to 9.5 years))
- Percent Change From Baseline in Renal Function Measured by the Glomerular Filtration Rate (GFR)(Enrollment through end of study (up to 9.5 years))
- Percent Change From Baseline in Total Cholesterol(Enrollment through end of study (up to 9.5 years))
- Percent Change From Baseline in Blood Glucose(Enrollment through end of study (up to 9.5 years))
- Percent Change From Baseline in Systolic Blood Pressure(Enrollment through end of study (up to 9.5 years))
- Percent Change From Baseline in Diastolic Blood Pressure(Enrollment through end of study (up to 9.5 years))