NCT00320606

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 The purpose of this study is to determine whether immunosuppressive drugs can be safely withdrawn over a minimum of 9 months from children who received liver transplants at least 4 years ago.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
20

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Jun 2006

Longer than P75 for phase_1

Geographic Reach
1 country

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 28, 2006

Completed
5 days until next milestone

First Posted

Study publicly available on registry

May 3, 2006

Completed
1 month until next milestone

Study Start

First participant enrolled

June 5, 2006

Completed
3.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 30, 2009

Completed
1.6 years until next milestone

Results Posted

Study results publicly available

July 6, 2011

Completed
5.7 years until next milestone

Study Completion

Last participant's last visit for all outcomes

March 13, 2017

Completed
Last Updated

September 20, 2018

Status Verified

August 1, 2018

Enrollment Period

3.5 years

First QC Date

April 28, 2006

Results QC Date

June 8, 2011

Last Update Submit

August 22, 2018

Conditions

Keywords

immunosuppression withdrawal (IS)anti-rejection drugstoleranceallograft function

Outcome Measures

Primary Outcomes (1)

  • Proportion of Participants Successfully Withdrawn From Immunosuppression

    Participants were considered successfully withdrawn from immunosuppression if they remained off immunosuppression for at least one year with normal allograft function.

    1 year after completion of immunosuppression withdrawal

Secondary Outcomes (10)

  • Number of Participants Who Suffered Graft Loss or Died Following Initiation of Immunosuppression Withdrawal

    Enrollment through end of study (up to 9.5 years)

  • 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

    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)

  • Immunosuppression-Free Duration

    Completion of Withdrawal to either end of trial participation (up to 9.5 years) or time to restarting immunosuppression

  • Distribution of Histologic Severity Among Rejection Episodes

    Start of immunosuppressive withdrawal to rejection through end of study (up to 9.5 years)

  • Number of Participants Experiencing Adverse Events by Severity

    Enrollment through end of study (up to 9.5 years)

  • +5 more secondary outcomes

Study Arms (1)

Immunosuppression Withdrawal

EXPERIMENTAL

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

Interventions

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.

Also known as: ISW
Immunosuppression Withdrawal

Eligibility Criteria

Age4 Years - 18 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • 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
  • Willing to participate in this study

You may not qualify if:

  • 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
  • % increase in dose of current immunosuppressive drug
  • HIV infection
  • Hepatitis B or C virus infection
  • Pregnancy or breastfeeding

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Children's Memorial Hospital

Chicago, Illinois, 60614, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Related Publications (4)

  • Reding R. Long-term complications of immunosuppression in pediatric liver recipients. Acta Gastroenterol Belg. 2005 Oct-Dec;68(4):453-6.

    PMID: 16433002BACKGROUND
  • 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.

  • 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.

  • 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.

Related Links

Results Point of Contact

Title
Director, Clinical Research Program
Organization
DAIT/NIAID

Study Officials

  • Sandy Feng, MD

    University of California, San Francisco

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Model Details: Recipients of parental living-donor liver allografts will undergo gradual withdrawal as tolerated of immunosuppression with the goal of complete withdrawal.
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 28, 2006

First Posted

May 3, 2006

Study Start

June 5, 2006

Primary Completion

November 30, 2009

Study Completion

March 13, 2017

Last Updated

September 20, 2018

Results First Posted

July 6, 2011

Record last verified: 2018-08

Data Sharing

IPD Sharing
Will share

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
More information

Available IPD Datasets

Individual Participant Data Set (SDY662:WISP-R ITN029ST)Access
Study summary, -schematic, -detailed description, -download packages et al. (SDY662:WISP-R ITN029ST)Access
Individual Participant Data Set (WISP-R ITN029ST)Access
Study protocol synopsis, -navigator, abstracts and manuscripts, datasets et al. (WISP-R ITN029ST)Access

Locations