A Cohort Study of Operationally Tolerant Allograft Recipients

Study Overview
=================
Brief Summary
-----------------
Antirejection medicines, also known as immunosuppressive drugs, are prescribed to organ transplant recipients to prevent their bodies from rejecting the new organ. Some organ transplant recipients can stop taking anti-rejection medicines without rejecting their transplanted organ (this is called 'tolerance'). The purpose of this study will collect samples and data from 'tolerant' liver or kidney transplant recipients in order to find out: The purpose of this study is to collect samples and data in order to find out: How long liver or kidney transplant recipients can remain tolerant; What happens in the tolerant recipient's body over time; and If there are patterns in the body that are linked to tolerance.

Detailed Description
-----------------
This is a multi-center, prospective, observational study in which operationally tolerant recipients of liver or kidney allografts will be followed longitudinally, with annual collections of clinical data and biological samples. All participants will be followed for the duration of the study, regardless of changes in their tolerance status. Participants will be recruited by three main pathways: Tolerant participants from current and past Immune Tolerance Network (ITN) trials, including those who have already completed trial participation and those who are anticipated to complete trial participation, Tolerant participants referred by ITN affiliated investigators, academic and community transplant physicians and directly through outreach to transplant affinity groups such as the National Kidney Foundation (NKF), and Tolerant participants from the general transplant community who are reachable through general contact channels such as the ITN website, word-of-mouth referrals from existing participants, and social media.

Official Title
-----------------
A Prospective Cohort Study of Operationally Tolerant Allograft Recipients (ITN063ST)

Conditions
-----------------
Kidney Transplant, Liver Transplant

Intervention / Treatment
-----------------
* Procedure: Blood Draw


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Recipient of single organ liver or kidney allograft from a living or deceased donor; At screening, operationally tolerant, as defined by: Absence of any immunosuppressive therapy for ≥52 weeks prior to the screening visit, and No evidence of allograft rejection in the 52 weeks prior to the screening visit, based on the allograft recipient's medical history. Normal allograft function, defined as: For liver transplant recipients: Liver function tests (ALT, GGT) both less than or equal to the upper limit of normal (ULN); and, For kidney transplant recipients: Serum creatinine value corresponds to an estimated GFR > 45 ml/min/1.73 m^2. Receiving regular follow-up for a kidney or liver transplant by a local physician: --Participants must be willing to allow the study team to contact and share medical information with this local physician. Ability to sign informed consent. Exclusion Criteria: Current malignancy requiring recent surgery, ongoing chemotherapy, or radiation; Transplant of another organ; Current drug or alcohol dependency; Any medical condition that in the opinion of the principal investigator would interfere with safe completion of the trial; and Inability to comply with the study visit schedule and required assessments.
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Operationally Tolerant Kidney or Liver Allograft Recipients<br>Operational tolerance at baseline is defined as: An absence of any immunosuppressive therapy for ≥ 52 weeks prior to the screening visit; No evidence of allograft rejection in the 52 weeks prior to the screening visit (Day 0), based on the participant's medical history; and Normal and stable allograft function at screening visit defined as- For liver transplant recipients: Liver function tests (ALT, GGT) both less than or equal to the upper limit of normal (ULN) For kidney transplant recipients: Serum creatinine value corresponds to an estimated glomerular filtration rate (GFR) > 45 ml/min/1.73 m^2. | Procedure: Blood Draw<br> <br> * Other names: Venipuncture;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Loss of Operational Tolerance | A participant is considered to have operational tolerance if they are off all immunosuppression medication while continuing to have stable allograft function and no rejection. For these participants, the date of operational tolerance is considered as 52 weeks from the participant's last documented dose of immunosuppression. A participant will be considered to have lost operational tolerance if they experience rejection, have loss of stable allograft function (in the absence of confounding factors), or restart immunosuppression. The endpoint was analyzed using Kaplan-Meier survival estimate and associated two-sided 95% confidence interval, using a delayed-entry model with left-truncation of survival times by censoring the time from achieving operational tolerance at the time of study enrollment. The survival estimate is at the time of the last of event. | From operational tolerance to ITN063ST study completion, assessed up to 60 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Development of Anti-Human Leukocyte Antigen (HLA) Antibody or Donor Specific Antibodies (DSA) | Time to development of either: de novo HLA antibodies (anti-HLA Ab) post-transplant. Alloantibody is defined as an antibody produced following the introduction of an alloantigen into the system of an individual lacking that particular antigen; OR Donor Specific Antibodies (DSA), a newly developed alloantibody that is against the donor organ. Alloantibodies are important mediators of acute and chronic rejection. **These data are not yet available.** | Day 0 (Study Enrollment) to Study Completion (Up to 3.7 years) | 
| Number of Participants With Biopsy-Proven or Clinical Acute Rejection, Steroid Resistant Rejection and/or Chronic Rejection | Number of participants with acute rejection, steroid resistant rejection and/or chronic rejection. Criteria employed for acute and chronic rejection: Banff guidelines. | Day 0 (Study Enrollment) to Study Completion (Up to 3.7 years) | 
| Number of Participants With Graft Loss, Not Including Death With a Functioning Graft | A participant is considered to have graft loss when the participant is retransplanted with another donor kidney, relisted for transplantation, or dies with a non-functioning graft. | Day 0 (Study Enrollment) to Study Completion (Up to 3.7 years) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
single organ liver or kidney allograft, operationally tolerant allograft recipients, longitudinal follow-up