Clinical trial NCT00320606: Withdrawal of Immunosuppression in Pediatric Liver Transplant Recipients
Official title: Immunosuppression Withdrawal for Pediatric Living-donor Liver Transplant Recipients (ITN029ST)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Liver Transplant
Liver Transplantation
Keywords: immunosuppression withdrawal (IS)
anti-rejection drugs
tolerance
allograft function
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Immune Tolerance Network (ITN)
First posted: 2006-05-03
Enrollment: 20
Sex: ALL
Minimum age (years): 4
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Recipients of parental living-donor liver allografts will undergo gradual withdrawal as tolerated of immunosuppression with the goal of complete withdrawal.
Primary purpose: TREATMENT

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 The purpose of this study is to determine whether immunosuppressive drugs can be safely withdrawn over a minimum of 9 months from children who received liver transplants at least 4 years ago.

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.

Eligibility 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

Primary outcomes:
measure: Proportion of Participants Successfully Withdrawn From Immunosuppression
timeFrame: 1 year after completion of immunosuppression withdrawal
Secondary outcomes:
measure: Number of Participants Who Suffered Graft Loss or Died Following Initiation of Immunosuppression Withdrawal
timeFrame: Enrollment through end of study (up to 9.5 years)
measure: 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
timeFrame: 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)
measure: Immunosuppression-Free Duration
timeFrame: Completion of Withdrawal to either end of trial participation (up to 9.5 years) or time to restarting immunosuppression
measure: Distribution of Histologic Severity Among Rejection Episodes
timeFrame: Start of immunosuppressive withdrawal to rejection through end of study (up to 9.5 years)
measure: Number of Participants Experiencing Adverse Events by Severity
timeFrame: Enrollment through end of study (up to 9.5 years)
measure: Percent Change From Baseline in Renal Function Measured by the Glomerular Filtration Rate (GFR)
timeFrame: Enrollment through end of study (up to 9.5 years)
measure: Percent Change From Baseline in Total Cholesterol
timeFrame: Enrollment through end of study (up to 9.5 years)
measure: Percent Change From Baseline in Blood Glucose
timeFrame: Enrollment through end of study (up to 9.5 years)
measure: Percent Change From Baseline in Systolic Blood Pressure
timeFrame: Enrollment through end of study (up to 9.5 years)
measure: Percent Change From Baseline in Diastolic Blood Pressure
timeFrame: Enrollment through end of study (up to 9.5 years)
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Chicago
country: United States
facility: Children's Memorial Hospital
state: Illinois
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
Study officials:
affiliation: University of California, San Francisco
name: Sandy Feng, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Reding R. Long-term complications of immunosuppression in pediatric liver recipients. Acta Gastroenterol Belg. 2005 Oct-Dec;68(4):453-6.
citation: Feng S, Ekong UD, Lobritto SJ, Demetris AJ, Roberts JP, Rosenthal P, Alonso EM, Philogene MC, Ikle D, Poole KM, Bridges ND, Turka LA, Tchao NK. Complete immunosuppression withdrawal and subsequent allograft function among pediatric recipients of parental living donor liver transplants. JAMA. 2012 Jan 18;307(3):283-93. doi: 10.1001/jama.2011.2014.
citation: Perito ER, Mohammad S, Rosenthal P, Alonso EM, Ekong UD, Lobritto SJ, Feng S. Posttransplant metabolic syndrome in the withdrawal of immunosuppression in Pediatric Liver Transplant Recipients (WISP-R) pilot trial. Am J Transplant. 2015 Mar;15(3):779-85. doi: 10.1111/ajt.13024. Epub 2015 Feb 3.
citation: Feng S, Demetris AJ, Spain KM, Kanaparthi S, Burrell BE, Ekong UD, Alonso EM, Rosenthal P, Turka LA, Ikle D, Tchao NK. Five-year histological and serological follow-up of operationally tolerant pediatric liver transplant recipients enrolled in WISP-R. Hepatology. 2017 Feb;65(2):647-660. doi: 10.1002/hep.28681. Epub 2016 Jul 27.