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

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ClinicalTrials.gov Identifier: NCT00320606
Recruitment Status : Completed
First Posted : May 3, 2006
Results First Posted : July 6, 2011
Last Update Posted : September 20, 2018
Sponsor:
Collaborator:
Immune Tolerance Network (ITN)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

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 The purpose of this study is to determine whether immunosuppressive drugs can be safely withdrawn over a minimum of 9 months from children who received liver transplants at least 4 years ago.

Condition or disease Intervention/treatment Phase
Liver Transplant Liver Transplantation Drug: Immunosuppression Withdrawal Phase 1

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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
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)
Actual Study Start Date : June 5, 2006
Actual Primary Completion Date : November 30, 2009
Actual Study Completion Date : March 13, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.

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.

Drug: Immunosuppression Withdrawal
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 Name: ISW




Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. Number of Participants Who Suffered Graft Loss or Died Following Initiation of Immunosuppression Withdrawal [ Time Frame: Enrollment through end of study (up to 9.5 years) ]
    Participants who died while on the study for any reason as well as participants that experienced the loss of their transplant while a participant in the study.

  2. 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 [ Time Frame: 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) ]
    The number of days between the start of immunosuppression (IS) withdrawal and the first episode of acute rejection (either clinical rejection or based on BANFF criteria), second episode of rejection that did not require treatment, or the first diagnosis of chronic rejection.

  3. Immunosuppression-Free Duration [ Time Frame: Completion of Withdrawal to either end of trial participation (up to 9.5 years) or time to restarting immunosuppression ]
    The number of months between the end of immunosuppression withdrawal and either the end of trial participation or the time of restarting immunosuppression

  4. Distribution of Histologic Severity Among Rejection Episodes [ Time Frame: Start of immunosuppressive withdrawal to rejection through end of study (up to 9.5 years) ]
    The number of participants within each level of histologic severity based on BANFF grading criteria (Mild, Moderate, Severe).

  5. Number of Participants Experiencing Adverse Events by Severity [ Time Frame: Enrollment through end of study (up to 9.5 years) ]
    The results provide the total number of participants experiencing adverse events (AEs). Participants experiencing AEs are stratified into five severity categories: mild, moderate, severe, life-threatening, and death, based on National Cancer Institute--Common Terminology Criteria (NCI-CTCAE) Version 3.0.

  6. Percent Change From Baseline in Renal Function Measured by the Glomerular Filtration Rate (GFR) [ Time Frame: Enrollment through end of study (up to 9.5 years) ]
    Percent change from baseline at each annual visit. The bedside Schwartz equation was used to estimate GFR from serum creatinine and height in children. Baseline serum creatinine was utilized in the equation, defined as the creatinine value at the start of IS tapering. Baseline height was utilized in the equation, defined as the last height recorded prior to the start of IS tapering. Serum creatinine measurements and height measurements at the annual visits were used to calculate the annual GFR. When height value was not available, the height collected prior to the annual visit was used in the GFR calculation. M12 and M24 visits represent Medium Frequency visits; L12 and L24 represent low frequency visits, and E12-48 represent extended follow-up visits.

  7. Percent Change From Baseline in Total Cholesterol [ Time Frame: Enrollment through end of study (up to 9.5 years) ]
    Percent change from baseline in total serum cholesterol. Cholesterol is a waxy substance your body needs to build cells, but too much can be a problem since it can build-up in arteries. Narrowed arteries can result in heart attack or stroke. This outcome looks at the percent change from baseline (cholesterol level at the start of IS tapering) to each annual visit. M12 and M24 visits represent Medium Frequency visits; L12 and L24 represent low frequency visits, and E12-48 represent extended follow-up visits.

  8. Percent Change From Baseline in Blood Glucose [ Time Frame: Enrollment through end of study (up to 9.5 years) ]
    Glucose, a sugar, is an energy source that the body relies on to properly function. If levels are too high for a long period of time, diabetes can develop. Diabetes can result in many long-term complications such as eye, kidney, and nerve damage, stroke, and cardiovascular complications. The outcome looks at the percent change from baseline (glucose level at the start of tapering) to each annual visit. M12 and M24 visits represent Medium Frequency visits; L12 and L24 represent low frequency visits, and E12-48 represent extended follow-up visits.

  9. Percent Change From Baseline in Systolic Blood Pressure [ Time Frame: Enrollment through end of study (up to 9.5 years) ]
    Systolic blood pressure (BP) measures the pressure on the blood vessels when the heart is beats and thus is pushing blood to the rest of the body. This outcome assesses the percent change from baseline (systolic blood pressure measurement at the start of tapering) to each annual visit. M12 and M24 visits represent Medium Frequency visits; L12 and L24 represent low frequency visits, and E12-48 represent extended follow-up visits.

  10. Percent Change From Baseline in Diastolic Blood Pressure [ Time Frame: Enrollment through end of study (up to 9.5 years) ]
    Diastolic blood pressure (BP) measures the pressure in the arteries when the heart is a rest and is thus filled with blood. This outcome assesses the percent change from baseline (diastolic blood pressure measurement at the start of IS tapering) to each annual visit. M12 and M24 visits represent Medium Frequency visits; L12 and L24 represent low frequency visits, and E12-48 represent extended follow-up visits.



Information from the National Library of Medicine

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Ages Eligible for Study:   4 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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
National Institute of Allergy and Infectious Diseases (NIAID)
Immune Tolerance Network (ITN)
Investigators
Principal Investigator: Sandy Feng, MD University of California, San Francisco
  Study Documents (Full-Text)

Documents provided by National Institute of Allergy and Infectious Diseases (NIAID):
Study Protocol  [PDF] April 19, 2011
Statistical Analysis Plan  [PDF] April 23, 2010


Additional Information:
Study Data/Documents: Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Identifier: SDY662:WISP-R ITN029ST
ImmPort study identifier is Study ID is SDY662:WISP-R ITN029ST
Study summary, -schematic, -detailed description, -download packages et al.  This link exits the ClinicalTrials.gov site
Identifier: SDY662:WISP-R ITN029ST
ImmPort study identifier is Study ID is SDY662:WISP-R ITN029ST
Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Identifier: WISP-R ITN029ST
TrialShare is a clinical trials research portal developed by the Immune Tolerance Network (ITN) that makes data from the consortium's clinical trials publicly available without charge. Creating an account for ITN TrialShare is free and allows for searching studies of interest.
Study protocol synopsis, -navigator, abstracts and manuscripts, datasets et al.  This link exits the ClinicalTrials.gov site
Identifier: WISP-R ITN029ST
TrialShare is a clinical trials research portal developed by the Immune Tolerance Network (ITN) that makes data from the consortium's clinical trials publicly available without charge. Creating an account for ITN TrialShare is free and allows for searching studies of interest.

Publications of Results:
Other Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00320606     History of Changes
Other Study ID Numbers: DAIT ITN029ST
First Posted: May 3, 2006    Key Record Dates
Results First Posted: July 6, 2011
Last Update Posted: September 20, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Participant level data and additional study materials are available to the public in: 1.) the Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from Division of Allergy, Immunology, and Transplantation (DAIT)-funded grants and contracts and 2.) TrialShare, the Immune Tolerance Network (ITN) Clinical Trials Research Portal.
Time Frame: Already available to the public.
Access Criteria: Available to the public. Study ID is SDY662:WISP-R ITN029ST
URL: http://www.immport.org/immport-open/public/study/study/displayStudyDetail/SDY662

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
immunosuppression withdrawal (IS)
anti-rejection drugs
tolerance
allograft function