Clinical trial NCT01338779: Study of Tolerant Kidney Transplant Recipients
Official title: Identification and Mechanistic Investigations of Tolerant Transplant Recipients
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Transplant Rejection
Kidney Transplantation
Renal Transplantation
Renal Transplant
Transplant Tolerance
Keywords: Tolerance
Renal
Allograft
B Cell Signature
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Immune Tolerance Network (ITN)
First posted: 2011-04-20
Enrollment: 197
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: * Primary Care Clinics
* Major Kidney (Renal) Transplant Programs

Brief summary: 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.

Detailed description: 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).

Eligibility criteria: 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.

Primary outcomes:
measure: To identify individuals who have received a kidney transplant and who have achieved a state of immune tolerance to graft
timeFrame: 0 to 11 years
measure: To create an electronic registry of data on the tolerant and comparison groups that will serve as the basis for statistical analyses
timeFrame: 0 to 11 years
measure: To use data from the registry to perform classical tests of hypotheses regarding the establishment of immune tolerance
timeFrame: 0 to 11 years
measure: 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
timeFrame: 0 to 11 years
Secondary outcomes:
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Bethesda
country: United States
facility: NIH Clinical Center
state: Maryland
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
Study officials:
affiliation: Emory University
name: Kenneth Newell, MD, PhD
role: STUDY_CHAIR
References:
citation: Schroppel B, Heeger PS. Gazing into a crystal ball to predict kidney transplant outcome. J Clin Invest. 2010 Jun;120(6):1803-6. doi: 10.1172/JCI43286. Epub 2010 May 24.
citation: Newell KA, Asare A, Kirk AD, Gisler TD, Bourcier K, Suthanthiran M, Burlingham WJ, Marks WH, Sanz I, Lechler RI, Hernandez-Fuentes MP, Turka LA, Seyfert-Margolis VL; Immune Tolerance Network ST507 Study Group. Identification of a B cell signature associated with renal transplant tolerance in humans. J Clin Invest. 2010 Jun;120(6):1836-47. doi: 10.1172/JCI39933. Epub 2010 May 24.
citation: Haynes LD, Jankowska-Gan E, Sheka A, Keller MR, Hernandez-Fuentes MP, Lechler RI, Seyfert-Margolis V, Turka LA, Newell KA, Burlingham WJ. Donor-specific indirect pathway analysis reveals a B-cell-independent signature which reflects outcomes in kidney transplant recipients. Am J Transplant. 2012 Mar;12(3):640-8. doi: 10.1111/j.1600-6143.2011.03869.x. Epub 2011 Dec 7.
citation: Newell KA, Asare A, Sanz I, Wei C, Rosenberg A, Gao Z, Kanaparthi S, Asare S, Lim N, Stahly M, Howell M, Knechtle S, Kirk A, Marks WH, Kawai T, Spitzer T, Tolkoff-Rubin N, Sykes M, Sachs DH, Cosimi AB, Burlingham WJ, Phippard D, Turka LA. Longitudinal studies of a B cell-derived signature of tolerance in renal transplant recipients. Am J Transplant. 2015 Nov;15(11):2908-20. doi: 10.1111/ajt.13480. Epub 2015 Oct 13.
citation: Yu J, Steck AK, Babu S, Yu L, Miao D, McFann K, Hutton J, Eisenbarth GS, Klingensmith G. Single nucleotide transcription factor 7-like 2 (TCF7L2) gene polymorphisms in antiislet autoantibody-negative patients at onset of diabetes. J Clin Endocrinol Metab. 2009 Feb;94(2):504-10. doi: 10.1210/jc.2007-2694. Epub 2008 Dec 2.
citation: Brennan DC, Shannon MB, Koch MJ, Polonsky KS, Desai N, Shapiro J. Portal vein thrombosis complicating islet transplantation in a recipient with the Factor V Leiden mutation. Transplantation. 2004 Jul 15;78(1):172-3. doi: 10.1097/01.tp.0000128332.71657.ea. No abstract available.