Study of Tolerant Kidney Transplant Recipients (FACTOR)

• ClinicalTrials.gov Identifier: NCT01338779
• Recruitment Status: Completed
• First Posted: April 20, 2011
• Last Update Posted: September 30, 2016
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborator: Immune Tolerance Network (ITN)
• Information provided by (Responsible Party): National Institute of Allergy and Infectious Diseases (NIAID)

Study Description

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.

Condition or disease
Transplant Rejection; Kidney Transplantation; Renal Transplantation; Renal Transplant; Transplant Tolerance

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).

Study Design

• Study Type: Observational
• Actual Enrollment: 197 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Identification and Mechanistic Investigations of Tolerant Transplant Recipients
• Study Start Date: May 2004
• Actual Primary Completion Date: August 2015
• Actual Study Completion Date: August 2015

Groups and Cohorts

Group/Cohort
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.

Outcome Measures

Primary Outcome Measures :

1. 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 ]
2. 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 ]
3. To use data from the registry to perform classical tests of hypotheses regarding the establishment of immune tolerance [ Time Frame: 0 to 11 years ]
4. 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 ]

Biospecimen Retention:   Samples With DNA

blood, urine and tissue samples

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Probability Sample

Study Population

• Primary Care Clinics
• Major Kidney (Renal) Transplant Programs

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.

Contacts and Locations

Locations

United States, Georgia

Emory University

Atlanta, Georgia, United States, 30322

United States, Maryland

NIH Clinical Center

Bethesda, Maryland, United States, 20814

United States, Washington

Swedish Medical Center

Seattle, Washington, United States, 98104

United States, Wisconsin

University of Wisconsin

Madison, Wisconsin, United States, 53792

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Immune Tolerance Network (ITN)

Investigators

• Study Chair: Kenneth Newell, MD, PhD; Emory University

More Information

Additional Information:

National Institute of Allergy and Infectious Diseases (NIAID) 

Immune Tolerance Network (ITN) 

Study Data/Documents: Individual Participant Data Set 

Identifier: ImmPort Study ID: SDY546

Study Protocol 

Identifier: ImmPort Study ID: SDY546

Study summary,-design, demographics,mechanistic assays,-study files et al. 

Identifier: ImmPort Study ID: SDY546

Individual Participant Data Set 

Identifier: Study ID: FACTOR/ITN507ST
FACTOR/ITN507ST is the Study Identifier in the ITN TrialShare Clinical Trials Research Portal.

Original articles w/data and reports; abstracts et al. 

Identifier: Study ID: FACTOR/ITN507ST
FACTOR/ITN507ST is the Study Identifier in the ITN TrialShare Clinical Trials Research Portal.

Publications of Results:

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.

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.

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.

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.

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.

Other Publications:

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.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT01338779
• Obsolete Identifiers: NCT00083655
• Other Study ID Numbers: DAIT ITN507ST
• First Posted: April 20, 2011
• Last Update Posted: September 30, 2016
• Last Verified: September 2016

Individual Participant Data (IPD) Sharing Statement:

• 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.

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Tolerance; Renal; Allograft; B Cell Signature