Withdrawal of Immunosuppression in Pediatric Liver Transplant Recipients (WISP-R)
|Liver Transplant Immunosuppression||Drug: Gradual withdrawal of immunosuppressive medication||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Intervention Model Description:
Recipients of parental living-donor liver allografts will undergo gradual withdrawal as tolerated of immunosuppression with the goal of complete withdrawal.Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Immunosuppression Withdrawal for Pediatric Living-donor Liver Transplant Recipients (ITN029ST)|
- Proportion of Subjects Successfully Withdrawn From Immunosuppression [ Time Frame: 1 year after completion of immunosuppression withdrawal ]Subjects were considered successfully withdrawn from immunosuppression if they remained off immunosuppression for at least one year with normal allograft function
- Proportion of Patients Who Suffer Graft Loss or Die Following Initiation of Immunosuppression Withdrawal [ Time Frame: 1 year ]
- Time From Start of Immunosuppression to the First Episode of Acute Rejection or to Diagnosis of Chronic Rejection [ Time Frame: Immunosuppression to first acute rejection or diagnosis of chronic rejection ]
- Distribution of Histologic Severity Among Rejection Episodes [ Time Frame: Immunosuppression to rejection ]
- Incidence of Adverse Events [ Time Frame: throughout trial ]
- Changes in Renal Function, Blood Pressure, Cholesterol Level, and Glucose Control [ Time Frame: throughout trial ]
|Study Start Date:||May 2006|
|Study Completion Date:||March 2017|
|Primary Completion Date:||August 2010 (Final data collection date for primary outcome measure)|
Experimental: 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.
Patients 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.
Drug: Gradual withdrawal of immunosuppressive medication
With high dose, daily dose reduction by 25% for 8 weeks. With low dose, daily dose reduction by 25% for 4 weeks.
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 patients 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00320606
|United States, California|
|University of California, San Francisco|
|San Francisco, California, United States, 94143|
|United States, Illinois|
|Children's Memorial Hospital|
|Chicago, Illinois, United States, 60614|
|United States, New York|
|Columbia University Medical Center|
|New York, New York, United States, 10032|
|Principal Investigator:||Sandy Feng, MD||University of California, San Francisco|