Study of Tolerant Kidney Transplant Recipients

NCT01338779 | Completed DMC

• 1 other identifier: DAIT ITN507ST
• Study Type: observational
• Target: 197
• Locations: 1 country
• Sites: 4

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.

Conditions

Transplant Rejection; Kidney Transplantation; Renal Transplantation; Renal Transplant; Transplant Tolerance

Keywords

Tolerance; Renal; Allograft; B Cell Signature

Outcome Measures

Primary Outcomes (4)

• To identify individuals who have received a kidney transplant and who have achieved a state of immune tolerance to graft

  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

  0 to 11 years

• To use data from the registry to perform classical tests of hypotheses regarding the establishment of immune tolerance

  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

  0 to 11 years

Study Arms (11)

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.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

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

You may qualify if:

• Must be a renal transplant recipient or living donor
• Provide informed consent

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Immune Tolerance Network (ITN): collaborator

Study Sites (4)

Emory University

Atlanta, Georgia, 30322, United States

Location

NIH Clinical Center

Bethesda, Maryland, 20814, United States

Location

Swedish Medical Center

Seattle, Washington, 98104, United States

Location

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Related Publications (6)

• 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.

  PMID: 20501950 BACKGROUND

• 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.

  PMID: 20501946 RESULT

• 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.

  PMID: 22151236 RESULT

• 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.

  PMID: 26461968 RESULT

• 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.

  PMID: 19050058 RESULT

• 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.

  PMID: 15257060 RESULT

Related Links

• National Institute of Allergy and Infectious Diseases (NIAID)
• Immune Tolerance Network (ITN)

Biospecimen

Retention: SAMPLES WITH DNA

blood, urine and tissue samples

Study Officials

• Kenneth Newell, MD, PhD

  Emory University

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2011
• First Posted: April 20, 2011
• Study Start: May 1, 2004
• Primary Completion: August 1, 2015
• Study Completion: August 1, 2015
• Last Updated: September 30, 2016

Record last verified: 2016-09

Data Sharing

• IPD Sharing: Will share

Locations

US (4)