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Completed

NCT Number: NCT00320606

Withdrawal of Immunosuppression in Pediatric Liver Transplant Recipients

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 The purpose of this study is to determine whether immunosuppressive drugs can be safely withdrawn over a minimum of 9 months from children who received liver transplants at least 4 years ago.

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Key information

Conditions

Liver Transplant Liver Transplantation

Age range

4 year–18 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

University of California, San Francisco, San Francisco, California, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Immunosuppression withdrawal

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.

Other names: ISW

Primary outcomes

  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 outcomes

  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.

Sponsors and collaborators

Lead sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Nih

Collaborators

  • Immune Tolerance Network (ITN)

Registry information

Official study title

Immunosuppression Withdrawal for Pediatric Living-donor Liver Transplant Recipients (ITN029ST)

Acronym: WISP-R

Important dates

Study start
2006
Primary completion
2009
Study completion
2017
First posted
May 3, 2006
Registry last updated
Sep 20, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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