Study of Tolerant Kidney Transplant Recipients

NCT ID: NCT01338779

Last Updated: 2016-09-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

197 participants

Study Classification

OBSERVATIONAL

Study Start Date

2004-05-31

Study Completion Date

2015-08-31

Brief Summary

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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

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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).

Conditions

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Transplant Rejection Kidney Transplantation Renal Transplantation Renal Transplant Transplant Tolerance

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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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).

No interventions assigned to this group

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.

No interventions assigned to this group

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.

No interventions assigned to this group

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).

No interventions assigned to this group

Group 5 - kidney standard immunotherapy

Enrollment for group 5 is closed. Stable renal transplant recipients currently on standard immunosuppression.

No interventions assigned to this group

Group 6 - kidney chronic rejector

Enrollment for group 6 is closed. Chronic allograft nephropathy group.

No interventions assigned to this group

Group 7 - kidney identical twin

Enrollment for group 7 is closed.

No interventions assigned to this group

Group 8 - living kidney donors

Corresponding to recipients in group 1 or 4.

No interventions assigned to this group

Group 9 - healthy controls

Enrollment for group 9 is closed.

No interventions assigned to this group

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).

No interventions assigned to this group

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.

No interventions assigned to this group

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Immune Tolerance Network (ITN)

NETWORK

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Kenneth Newell, MD, PhD

Role: STUDY_CHAIR

Emory University

Locations

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Emory University

Atlanta, Georgia, United States

Site Status

NIH Clinical Center

Bethesda, Maryland, United States

Site Status

Swedish Medical Center

Seattle, Washington, United States

Site Status

University of Wisconsin

Madison, Wisconsin, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 20501950 (View on PubMed)

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.

Reference Type RESULT
PMID: 20501946 (View on PubMed)

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.

Reference Type RESULT
PMID: 22151236 (View on PubMed)

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.

Reference Type RESULT
PMID: 26461968 (View on PubMed)

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.

Reference Type RESULT
PMID: 19050058 (View on PubMed)

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.

Reference Type RESULT
PMID: 15257060 (View on PubMed)

Study Documents

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Document Type: Individual Participant Data Set

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

View Document

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

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

View Document

Related Links

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https://www.niaid.nih.gov/

National Institute of Allergy and Infectious Diseases (NIAID)

http://www.immunetolerance.org

Immune Tolerance Network (ITN)

Other Identifiers

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DAIT ITN507ST

Identifier Type: -

Identifier Source: org_study_id

NCT00083655

Identifier Type: -

Identifier Source: nct_alias

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