Grant: National Institute of Allergy and Infectious Diseases This is a registry trial collecting extensive demographic and clinical information, medical histories, and blood and urine samples of tolerant kidney transplant recipients. Initial goal was to enroll 225 participants over the course of the study and classify them into 1 of 11 groups (see section 3.3). As of protocol v7.0, enrollment and follow-up is closed to all groups except 1, 4, and 8. Currently, targets for enrollment are 50 participants for group 1 and 32 for group 4 over the course of the study. The maximum number of living donors who correspond to the transplant recipients in groups 1 and 4 will also be enrolled in group 8. This is a registry trial. Each participant will be asked to provide consent for the collection of extensive demographic and clinical information; medical histories; and blood and urine samples. Blood and urine samples collected will be used to perform specific assays (see section 7) to help define mechanisms of tolerance. In addition, specimens collected may be archived for use in future research assays. Initially, duration was 6 years. As of protocol version 11.0, enrollment and follow-up for groups 1, 4, and 8 will continue until the trial end date of August 2015.

Plan to Share IPD: Yes Plan Description: Participant level data access is available to the public in: 1.) the Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts; and 2.) TrialShare, the Immune Tolerance Network (ITN) Clinical Trials Research Portal.

instance of dataset

available with registration

FACTOR

National Institute of Allergy and Infectious Diseases (NIAID)

Retention: Samples With DNA Description: blood, urine and tissue samples

Group 1 - kidney tolerant Renal allograft recipients showing functional tolerance (normal and stable renal function) after discontinuation of immunosuppressive medications for at least 1 year (or based on the investigator's discretion). Group 2 - acceptor Enrollment for group 2 was closed. Renal transplant recipients with functioning allografts (not on dialysis) who had not received immunosuppressive medications for at least 1 year (or at investigator's discretion) but who had moderately impaired or gradually deteriorating renal function, defined as creatinine clearance (CrCl) < 40 mL/min and/or creatinine > 50% above baseline value, and thus did not qualify for group 1. Group 3 - kidney graft loss Enrollment for group 3 is closed. These were renal transplant recipients who had subsequently rejected and lost function of their transplanted kidney. Group 4 - kidney monotherapy Renal transplant recipients showing stable and normal renal function after receiving only prednisone 10 mg/day for at least 1 year (or based on the investigator's discretion). Group 5 - kidney standard immunotherapy Enrollment for group 5 is closed. Stable renal transplant recipients currently on standard immunosuppression. Group 6 - kidney chronic rejector Enrollment for group 6 is closed. Chronic allograft nephropathy group. Group 7 - kidney identical twin Enrollment for group 7 is closed. Group 8 - living kidney donors Corresponding to recipients in group 1 or 4. Group 9 - healthy controls Enrollment for group 9 is closed. Group 10 - liver tolerant Enrollment for group 10 is closed. Liver allograft recipients with functional tolerance (stable and normal liver function) after cessation of immunosuppressive medications for at least three years (or at investigator's discretion). Group 11 - liver standard immunotherapy Enrollment for group 11 is closed. Subjects with a liver transplant who never had an attempt made to discontinue gradually their immunosuppression and who are currently taking standard immunosuppressive medications and have stable and normal liver allograft function after at least 1 year of receiving these drugs.

Not Provided

registration required

Transplant Rejection Kidney Transplantation Renal Transplantation Renal Transplant Transplant Tolerance

Kenneth Newell, MD, PhD

Emory University

Study Chair

Study of Tolerant Kidney Transplant Recipients

197

To identify individuals who have received a kidney transplant and who have achieved a state of immune tolerance to graft [ Time Frame: 0 to 11 years ] To create an electronic registry of data on the tolerant and comparison groups that will serve as the basis for statistical analyses [ Time Frame: 0 to 11 years ] To use data from the registry to perform classical tests of hypotheses regarding the establishment of immune tolerance [ Time Frame: 0 to 11 years ] To use data from the registry to create and assess predictive statistical models to model such variables as clinical features, duration of tolerant state, and time to onset of immune sensitization [ Time Frame: 0 to 11 years ]

Not Provided

NC

Inclusion Criteria: Must be a renal transplant recipient or living donor Meet the criteria for inclusion in one of the study enrollment groups Provide informed consent Exclusion Criteria: AIDS [includes all HIV-infected persons who have less than 200 cells/mm(3) CD4+ T-lymphocytes/microL, or a CD4+ T-lymphocyte/micro liter or a CD4+ T-lymphocyte percent of total lymphocytes less than 14, or who have been diagnosed with an AIDS-defining condition as defined by the Centers for Disease Control and Prevention (CDC) Current malignancy requiring recent surgery, ongoing chemotherapy or radiation Acute systemic infections within 30 days prior to enrollment Pregnancy Transplant of another organ Note: Patients meeting any of the exclusion criteria, if identified to have been clinically tolerant prior to the occurrence of the excluding condition, will be enrolled and demographic data collected for the registry; however, the decision as to whether or not to collect blood, urine, and tissue samples will be deferred until the participant's condition improves and the clinically tolerant state persists.

2015-08-01

Identification and Mechanistic Investigations of Tolerant Transplant Recipients

The purpose of this multi-center (observational) registry study is to establish a database of clinical and laboratory information that may help to identify any unique characteristics of tolerant participants that differ from participants who reject their kidney after discontinuing immunosuppressive drugs.

Following kidney (renal) transplantation, one possible complication is rejection of the new kidney. This occurs as a results of the body's immune system attacking (or rejecting) the newly transplanted kidney. After transplant, medicines known as "immunosuppressive" or "anti-rejection" drugs are given to transplant recipients to help prevent rejection of the transplanted kidney. If a transplant recipient stops taking these medicines, they almost always reject their transplanted kidney. However, in some exceptionally rare instances, transplant recipients who stop taking these drugs do not reject their kidney, and the kidney keeps working. The recipients are said at that point to "tolerate" the transplanted kidney, and this condition is referred to as "tolerance". In this study, participants will be asked to provide consent for the collection of extensive demographic and clinical information; medical histories; and blood and urine samples. Blood and urine samples collected will be used to perform specific assays to help define mechanisms of tolerance. Originally the study included 11 groups as listed; however, at present only groups 1,4, and 8 remain active. Whereas the initial study duration was 6 years, this was extended to 11 years in order to follow over more extended time a B cell signature identified for tolerant kidney subjects and how this signature may change. (Refer to publications section: Newell, Kirk et al, J Clin Invest. 2010).

Observational Model: Cohort Time Perspective: Prospective

United States

2004-05-01

ITN TrialShare