Withdrawal of Immunosuppression in Pediatric Liver Transplant Recipients
Condition: Liver Transplant; Liver Transplantation
Study type: Interventional
Phase: Phase 1

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      can be safely withdrawn over a minimum of 9 months from children who received liver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.
    

Intervention name(s): Immunosuppression Withdrawal
Intervention type(s): Drug
Intervention description(s): 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.
Other intervention name(s): ISW
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
Keywords: immunosuppression withdrawal (IS); anti-rejection drugs; tolerance; allograft function