Withdrawal of Immunosuppression in Pediatric Liver Transplant Recipients (WISP-R)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Immune Tolerance Network (ITN)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00320606
First received: April 28, 2006
Last updated: June 27, 2014
Last verified: June 2014
  Purpose

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 The purpose of this study is to determine whether immunosuppressive drugs can be safely withdrawn over a minimum of 9 months from children who received liver transplants at least 4 years ago.


Condition Intervention Phase
Liver Transplant
Immunosuppression
Procedure: Gradual withdrawal of immunosuppressive medication
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Immunosuppression Withdrawal for Pediatric Living-donor Liver Transplant Recipients (ITN029ST)

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Proportion of Subjects Successfully Withdrawn From Immunosuppression [ Time Frame: 1 year after completion of immunosuppression withdrawal ] [ Designated as safety issue: Yes ]
    Subjects were considered successfully withdrawn from immunosuppression if they remained off immunosuppression for at least one year with normal allograft function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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • Distribution of Histologic Severity Among Rejection Episodes [ Time Frame: Immunosuppression to rejection ] [ Designated as safety issue: Yes ]
  • Incidence of Adverse Events [ Time Frame: throughout trial ] [ Designated as safety issue: Yes ]
  • Changes in Renal Function, Blood Pressure, Cholesterol Level, and Glucose Control [ Time Frame: throughout trial ] [ Designated as safety issue: Yes ]

Enrollment: 20
Study Start Date: May 2006
Estimated Study Completion Date: March 2017
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Procedure: 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.

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 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.

  Eligibility

Ages Eligible for Study:   4 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria for Liver Recipients:

  • Received liver from living parent donor
  • Received transplant at least 4 years prior to study entry
  • Less than 18 years of age at time of transplant
  • Parent or guardian willing to provide informed consent

Inclusion Criteria for Liver Donors:

  • Willing to participate in this study

Exclusion Criteria for Liver Recipients:

  • Underwent transplant because of liver failure related to autoimmune disease
  • Underwent transplant of a second organ simultaneously with or after liver transplant OR liver retransplantation
  • Receiving immunosuppression with more than one drug
  • 50% increase in dose of current immunosuppressive drug
  • HIV infection
  • Hepatitis B or C virus infection
  • Pregnancy or breastfeeding
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00320606

Locations
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
Sponsors and Collaborators
Immune Tolerance Network (ITN)
Investigators
Principal Investigator: Sandy Feng, MD University of California, San Francisco
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00320606     History of Changes
Other Study ID Numbers: DAIT ITN029ST
Study First Received: April 28, 2006
Results First Received: June 8, 2011
Last Updated: June 27, 2014
Health Authority: United States: Federal Government
United States: Institutional Review Board

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
allograft function
anti-rejection
immunosuppression withdrawal
liver transplant
liver transplantation
living donor transplant

Additional relevant MeSH terms:
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 21, 2014