Impact of Immunosuppressive Regimens on Polyomavirus-related Transplant Nephropathy

Polyomavirus Infections Clinical Trial

Official title:

Prospective Randomized Study to Characterize Risk Factors of Polyomavirus-related Transplant Nephropathy and the Impact of Three Immunosuppressive Regimens on Nephropathy Incidence

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00160966
• Other study ID #: NTx-PV-002
• Status: Completed
• Phase: Phase 4
• First received: September 8, 2005
• Last updated: March 27, 2017
• Start date: September 2004
• Est. completion date: March 2010

Study information

• Verified date: January 2017
• Source: University of Giessen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of this study is to characterize and evaluate risk factors of polyomavirus nephropathy (PVN) including the impact of three immunosuppressive regimens.

Description:

Polyomavirus nephropathy (PVN) is an emerging cause of renal transplant loss. Until now the risk factors of PVN are poorly understood. Tacrolimus (Tacr) and mycophenolate mofetil (MMF) are thought to be associated with a higher risk of developing PVN. However, the way in which Tacr or MMF might enhance the susceptibility for PVN remains largely unknown. In this prospective study we will analyze whether differences in immune-reactivity patterns (Th1, Th2, B cell and monocyte responses, sCD30, immunoregulatory antibodies) of renal transplant patients induced by different immunosuppressive regimens (cyclosporine A [CsA]/MMF, Tacr/MMF, Tacr/MMF with conversion to Tacr/Everolimus [ERL]) or by cytokine promoter gene polymorphisms may account for the different risks of developing PVN.

Comparison(s): renal transplant recipients stratified according to their relative immunological risk (group 1: low risk (primary recipients without pre-immunization [PRA < 5%]); group 2: moderate risk (group 2a: primary recipients with low pre-immunization [PRA 6-20%]; group 2b: re-transplanted patients); group 3: very high risk (re-transplanted patients with a history of vascular rejection or recipients of a first graft with high pre-immunization [PRA > 20%]) randomized to be treated with one of three immunosuppressive regimens (CsA/MMF, Tacr/MMF, Tacr/MMF with subsequent conversion to Tacr/ERL).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 108
• Est. completion date: March 2010
• Est. primary completion date: March 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Cadaver kidney and living donor kidney transplant recipients

• Primary, secondary, and tertiary transplant recipients

• Pre-immunized and not pre-immunized transplant recipients

• Age > 18 years

Exclusion Criteria:

• Contraindications against administration of one of the four study drugs

• History of severe gastrointestinal morbidity

• Age < 18 years

• Pregnant or breast feeding women

• Rejection of effective contraceptive methods with young women

• Combined kidney and islet cell transplantation

Related Conditions & MeSH terms

• Kidney Diseases
• Polyomavirus Infections

Intervention

Drug:
• Ciclosporin and Mycophenolate-mofetil
according to the Giessen protocol
• Tacrolimus and Mycophenolate-mofetil
according to Giessen protocol
• Tacrolimus and Mycophenolate-mofetil with change from Mycophenolate-mofetil to Everolimus
according to Giessen protocol

Locations

Country	Name	City	State
Germany	Department of Internal Medicine, University of Giessen	Giessen

Sponsors (5)

Lead Sponsor	Collaborator
University of Giessen	Astellas Pharma Inc, Heidelberg University, Hoffmann-La Roche, Novartis

Country where clinical trial is conducted

Germany, 

References & Publications (23)

Andrews CA, Shah KV, Daniel RW, Hirsch MS, Rubin RH. A serological investigation of BK virus and JC virus infections in recipients of renal allografts. J Infect Dis. 1988 Jul;158(1):176-81. — View Citation

Barri YM, Ahmad I, Ketel BL, Barone GW, Walker PD, Bonsib SM, Abul-Ezz SR. Polyoma viral infection in renal transplantation: the role of immunosuppressive therapy. Clin Transplant. 2001 Aug;15(4):240-6. — View Citation

Binet I, Nickeleit V, Hirsch HH, Prince O, Dalquen P, Gudat F, Mihatsch MJ, Thiel G. Polyomavirus disease under new immunosuppressive drugs: a cause of renal graft dysfunction and graft loss. Transplantation. 1999 Mar 27;67(6):918-22. — View Citation

Daniel V, Arzberger J, Melk A, Weimer R, Ruhenstroth A, Carl S, Wiesel M, Opelz G. Predictive indicators of rejection or infection in renal transplant patients. Transplant Proc. 1999 Feb-Mar;31(1-2):1364-5. — View Citation

Daniel V, Pasker S, Wiesel M, Carl S, Pomer S, Staehler G, Schnobel R, Weimer R, Opelz G. Cytokine monitoring of infection and rejection in renal transplant recipients. Transplant Proc. 1995 Feb;27(1):884-6. — View Citation

Hirsch HH, Knowles W, Dickenmann M, Passweg J, Klimkait T, Mihatsch MJ, Steiger J. Prospective study of polyomavirus type BK replication and nephropathy in renal-transplant recipients. N Engl J Med. 2002 Aug 15;347(7):488-96. — View Citation

Hirsch HH, Mohaupt M, Klimkait T. Prospective monitoring of BK virus load after discontinuing sirolimus treatment in a renal transplant patient with BK virus nephropathy. J Infect Dis. 2001 Dec 1;184(11):1494-5; author reply 1495-6. — View Citation

Hirsch HH. Polyomavirus BK nephropathy: a (re-)emerging complication in renal transplantation. Am J Transplant. 2002 Jan;2(1):25-30. Review. — View Citation

Nickeleit V, Hirsch HH, Zeiler M, Gudat F, Prince O, Thiel G, Mihatsch MJ. BK-virus nephropathy in renal transplants-tubular necrosis, MHC-class II expression and rejection in a puzzling game. Nephrol Dial Transplant. 2000 Mar;15(3):324-32. Review. — View Citation

Pelzl S, Opelz G, Daniel V, Wiesel M, Süsal C. Evaluation of posttransplantation soluble CD30 for diagnosis of acute renal allograft rejection. Transplantation. 2003 Feb 15;75(3):421-3. — View Citation

Süsal C, Döhler B, Opelz G. Graft-protective role of high pretransplantation IgA-anti-Fab autoantibodies: confirmatory evidence obtained in more than 4000 kidney transplants. The Collaborative Transplant Study. Transplantation. 2000 Apr 15;69(7):1337-40. — View Citation

Süsal C, Opelz G. Kidney graft failure and presensitization against HLA class I and class II antigens. Transplantation. 2002 Apr 27;73(8):1269-73. — View Citation

Süsal C, Pelzl S, Döhler B, Opelz G. Identification of highly responsive kidney transplant recipients using pretransplant soluble CD30. J Am Soc Nephrol. 2002 Jun;13(6):1650-6. — View Citation

Weimer R, Daniel V, Pomer S, Opelz G. B lymphocyte response as an indicator of acute renal transplant rejection. I. Immunoglobulin-secreting cells in peripheral blood. Transplantation. 1989 Oct;48(4):569-72. — View Citation

Weimer R, Daniel V, Pomer S, Opelz G. B lymphocyte response as an indicator of acute renal transplant rejection. II. Pretransplant and posttransplant B cell responses of m mitogen and donor cell-stimulated cultures. Transplantation. 1989 Oct;48(4):572-5. — View Citation

Weimer R, Daniel V, Zimmermann R, Schimpf K, Opelz G. Autoantibodies against CD4 cells are associated with CD4 helper defects in human immunodeficiency virus-infected patients. Blood. 1991 Jan 1;77(1):133-40. — View Citation

Weimer R, Melk A, Daniel V, Friemann S, Padberg W, Opelz G. Switch from cyclosporine A to tacrolimus in renal transplant recipients: impact on Th1, Th2, and monokine responses. Hum Immunol. 2000 Sep;61(9):884-97. — View Citation

Weimer R, Mytilineos J, Feustel A, Preiss A, Daniel V, Grimm H, Wiesel M, Opelz G. Mycophenolate mofetil-based immunosuppression and cytokine genotypes: effects on monokine secretion and antigen presentation in long-term renal transplant recipients. Transplantation. 2003 Jun 27;75(12):2090-9. — View Citation

Weimer R, Staak A, Süsal C, Streller S, Yildiz S, Pelzl S, Renner F, Dietrich H, Daniel V, Rainer L, Kamali-Ernst S, Ernst W, Padberg W, Opelz G. ATG induction therapy: long-term effects on Th1 but not on Th2 responses. Transpl Int. 2005 Feb;18(2):226-36. — View Citation

Weimer R, Streller S, Staak A, Heilke M, Li D, Dietrich H, Daniel V, Feustel A, Rainer L, Zinn S, Friemann S, Ernst W, Grimm H, Padberg W, Zimmermann T, Opelz G. Effects of three immunosuppressive regimens on CD4 helper function, B cell monocyte and cytokine responses in renal transplant recipients: 4-month follow-up of a prospective randomized study. Transplant Proc. 2002 Sep;34(6):2377-8. — View Citation

Weimer R, Süsal C, Yildiz S, Streller S, Pelzl S, Staak A, Renner F, Dietrich H, Daniel V, Feuring E, Kamali-Ernst S, Ernst W, Padberg W, Opelz G. sCD30 and neopterin as risk factors of chronic renal transplant rejection: impact of cyclosporine A, tacrolimus, and mycophenolate mofetil. Transplant Proc. 2005 May;37(4):1776-8. — View Citation

Weimer R, Zipperle S, Daniel V, Carl S, Staehler G, Opelz G. Pretransplant CD4 helper function and interleukin 10 response predict risk of acute kidney graft rejection. Transplantation. 1996 Dec 15;62(11):1606-14. — View Citation

Weimer R, Zipperle S, Daniel V, Pomer S, Staehler G, Opelz G. IL-6 independent monocyte/B cell defect in renal transplant recipients with long-term stable graft function. Transplantation. 1994 Jan;57(1):54-9. — View Citation

* Note: There are 23 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	incidence of polyomavirus associated transplant nephropathy (PVN)		2 years posttransplant
Primary	incidence of polyoma viremia		2 years posttransplant
Primary	urine polyomavirus concentration within the first two years post-transplant		2 years posttransplant
Secondary	patients' and grafts' survival		2 years posttransplant
Secondary	incidence of acute rejections		2 years posttransplant
Secondary	transplant function 1 and 2 years post-transplant		2 years posttransplant
Secondary	comparison of urine cytology and polymerase chain reaction (PCR) quantitative data regarding diagnosis of PVN		2 years posttransplant
Secondary	predictive value of immune parameters prognostically relevant for acute or chronic rejection		2 years posttransplant
Secondary	side effects of immunosuppressive drugs		2 years posttransplant