Viewing Study NCT00150891



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Last Modification Date: 2024-10-26 @ 9:14 AM
Study NCT ID: NCT00150891
Status: COMPLETED
Last Update Posted: 2007-05-10
First Post: 2005-09-06

Brief Title: Th1 Th2 and Monokine Responses as Risk Factors of Renal Transplant Rejection
Sponsor: University of Giessen
Organization: University of Giessen

Study Overview

Official Title: Role of Th1 Th2 and Monokine Responses as Risk Factors of Acute and Chronic Renal Transplant Rejection - Impact of Different Immunosuppressive Protocols
Status: COMPLETED
Status Verified Date: 2007-05
Last Known Status: None
Delayed Posting: No
If Stopped, Why?: Not Stopped
Has Expanded Access: False
If Expanded Access, NCT#: N/A
Has Expanded Access, NCT# Status: N/A
Acronym: None
Brief Summary: Chronic transplant rejection remains the main cause of late kidney graft loss We showed previously that patients with pretransplant CD4 helper defects and low in-vitro IL-10 responses demonstrated an extremely low risk of acute rejection and a significantly better 1- and 3-year graft function whereas pretransplant Th1 responses were not predictive Weimer R et al 1996 and 1998 In liver transplant recipients we found CD4 helper function and in-vitro IL-10 responses significantly decreased compared to CsA-treated patients Zipperle et al 1997 If the same effect will be demonstrated in renal transplant recipients Tacrolimus Tacr treatment might result in enhanced graft survival compared to CsA when CD4 helper function and in-vitro IL-10 responses of the individual patient are elevated Other studies of our group suggest a beneficial role of enhanced T-suppressor activity and of an IL-6 independent B cellmonocyte defect in the maintenance of long-term stable graft function whereas enhanced monokine secretion TNF-a GM-CSF IL-6 was found in chronic rejection Weimer et al 1990 1992 1994 1998

In the current randomized prospective study we will analyze the impact of CsA versus Tacr and of MMF versus azathioprine on Th1 Th2 and monokine responses and their predictive value regarding occurrence of acute and chronic rejection With a proposed follow-up of 5 years this study might enable a patient-tailored immunosuppressive therapy resulting in prolonged graft survival
Detailed Description: Chronic transplant rejection remains the main cause of late kidney graft loss We showed previously that patients with pretransplant CD4 helper defects and low in-vitro IL-10 responses demonstrated an extremely low risk of acute rejection and a significantly better 1- and 3-year graft function whereas pretransplant Th1 responses were not predictive Weimer R et al 1996 and 1998 In liver transplant recipients we found CD4 helper function and in-vitro IL-10 responses significantly decreased compared to CsA-treated patients Zipperle et al 1997 If the same effect will be demonstrated in renal transplant recipients Tacrolimus Tacr treatment might result in enhanced graft survival compared to CsA when CD4 helper function and in-vitro IL-10 responses of the individual patient are elevated Other studies of our group suggest a beneficial role of enhanced T-suppressor activity and of an IL-6 independent B cellmonocyte defect in the maintenance of long-term stable graft function whereas enhanced monokine secretion TNF-a GM-CSF IL-6 was found in chronic rejection Weimer et al 1990 1992 1994 1998

In the current randomized prospective study we will analyze the impact of CsA versus Tacr and of MMF versus azathioprine Aza 3 treatment groups CsAAza CsAMMF and TacrAza steroid and prophylactic ATG treatment according to the Giessen protocol on immune parameters and their predictive value regarding occurrence of acute and chronic rejection As immune parameters we will assess CD4 helper function in-vitro IL-4 and IL-10 responses of T cells and CD4 T cells respectively in allogeneic cocultures of patient T cells with control B cells and in PHA-stimulated T cell cultures T-cell dependent PWM-stimulated allogeneic cocultures and T-independent SAC I-stimulated B cell cultures immunoglobulin-secreting cell ISC responses B-cell IL-6 and IL-10 responses and monokine responses LPS-stimulated monocyte cultures pretransplant and 4 months 1 year 2 years and 5 years posttransplant Serum cytokines and easily measurable parameters as neopterin sIL-1RA and sCD30 will be assessed at the same time points The same is true for flow cytometric analysis of cytokine receptor adhesion molecule costimulator molecule and surface molecule expression respectively which play an important role in cell-cell interactions and tolerance induction Cytokine promoter gene polymorphisms will be determined to potentially enable pretransplant risk estimation To establish a broadly available and rapid diagnostic method we will compare the data of intracellular cytokine testing with the results of the much more difficult and time consuming coculture analyses used in our previous studies

With a proposed follow-up of 5 years this prospective randomized study might enable a patient-tailored immunosuppressive therapy resulting in better graft function and prolonged graft survival by preventing chronic allograft rejection

Weimer R Pomer S Staehler G Opelz G Increased T suppressor activity in renal transplant recipients with long-term stable graft function Clinical Transplantation 1990 4 280-286

Weimer R Zipperle S Daniel V Pomer S Staehler G Opelz G In vitro B cell response in long-term renal transplant recipients Transplant Proc 1992 246 2537-2538

Weimer R Zipperle S Daniel V Pomer S Staehler G Opelz G IL-6 independent monocyteB cell defect in renal transplant recipients with long-term stable graft function Transplantation 1994 571 54-59

Weimer R Zipperle S Daniel V Carl S Staehler G Opelz G Pretransplant CD4 helper function and IL-10 response predict risk of acute kidney graft rejection Transplantation 1996 6211 1606-1614

Zipperle S Weimer R Golling M Daniel V Otto G Opelz G Impaired T cell IL-10 secretion and CD4 helper function in liver transplant patients treated with tacrolimus Transplant Proc 1997 291-2 1079-1080

Weimer R Zipperle S Daniel V Carl S Staehler G Opelz G Superior 3-year kidney graft function in patients with impaired pretransplant Th2 responses Transplant Int 1998 11 Suppl 1 350-356

Study Oversight

Has Oversight DMC: None
Is a FDA Regulated Drug?: None
Is a FDA Regulated Device?: None
Is an Unapproved Device?: None
Is a PPSD?: None
Is a US Export?: None
Is an FDA AA801 Violation?: None