Immunoregulatory Effects of Immunoglobulin Induction Therapy in Renal Transplant Recipients

Renal Transplantation Clinical Trial

Official title:

Immunoglobulin Induction Therapy in Renal Transplant Recipients on Tacrolimus/Azathioprine or Tacrolimus/MMF: Effects on Th1, Th2, B Cell-/Monokine Responses and Immunoregulatory Autoantibody Levels

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00176059
• Other study ID #: NTx-Ig-003
• Status: Completed
• Phase: Phase 0
• First received: September 9, 2005
• Last updated: May 8, 2007
• Start date: October 2001
• Est. completion date: May 2006

Study information

• Verified date: May 2007
• Source: University of Giessen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

The aim of this randomized prospective study in renal transplant recipients is to investigate immunological short and long-term effects of an IVIG induction therapy.

Furthermore clinical endpoints (patient and graft survival, incidence of acute and chronic rejection, infectious diseases and graft function) up to three years posttransplant will be analyzed.

Description:

Intravenous immunoglobulin (IVIG) preparations are known to be effective in the treatment of various autoimmune and inflammatory disorders due to their immunomodulatory and antiinflammatory properties. It has been demonstrated that IVIG is effective in the treatment of acute vascular rejection and steroid resistant cellular rejection. Furthermore, IVIG has been used to inhibit production of lymphocytotoxic antibodies in highly sensitized patients so that successful cadaveric or living renal transplantation could be performed.

The aim of this randomized prospective study in renal transplant recipients is to investigate immunological short and long-term effects of an IVIG induction therapy on Th1, Th2 and B-cell/monocyte responses, expression of adhesion molecules, costimulatory factors and cytokine receptors and on secretion of immunoregulatory autoantibodies (anti-F(ab)-, anti-F(ab')2G-, anti-hinge autoantibodies). These autoantibodies have been shown to significantly affect the risk of chronic rejection and graft loss.

Furthermore, clinical endpoints (patient and gaft survival, incidence of acute and chronic rejection, infectious diseases and graft function) up to 3 years will be analyzed.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: May 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 14 Years and older

Eligibility

Inclusion Criteria:

• renal transplant recipients of the Giessen renal transplant unit

• cadaveric and living renal transplants

• first and retransplants

Exclusion Criteria:

• Contraindications against blood-taking (anaemia with hemoglobin < 9,5 g/l, hypotension)

• intravenous immunoglobulin therapy in the last half year before study entry

• Hyperimmunoglobulin therapy for severe CMV infection

• Pregnancy

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Kidney Failure, Chronic
• Renal Failure, Chronic
• Renal Transplantation

Intervention

Drug:
• intravenous immunoglobulins (IVIG)

Procedure:
• kidney transplantation

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, Aventis Pharmaceuticals, Heidelberg University, Hoffmann-La Roche

Country where clinical trial is conducted

Germany, 

References & Publications (17)

Staak A, Renner F, Suesal C, Dietrich H, Rainer L, Kamali-Ernst S, Ernst W, Padberg W, Opelz G, Weimer R. Immunoglobulin induction therapy in renal transplant recipients: Effects on immunoglobulin and regulatory antibody levels. Transplant Proc. 2006 Dec; — 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, Dörr C, Groth J, May G, Opelz G. Pretransplant serum IgA concentration and IgA-anti-Fab autoantibody activity as prognostic indicators of kidney graft survival. Transpl Int. 1994;7 Suppl 1:S586-9. — View Citation

Süsal C, Guo ZG, Terness P, Opelz G. Role of anti-IgG autoantibodies in kidney transplantation. Immunol Lett. 1990 Nov;26(2):121-5. — View Citation

Sùsal C, Kröpelin M, Groth J, Wiesel M, May G, Carl S, Staehler G, Opelz G. Protective effect of autoantibodies against the hinge region of human IgG in kidney graft recipients. Transplantation. 1996 Nov 27;62(10):1534-6. — View Citation

Süsal C, Kröpelin M, Wiesel M, Staehler G, Groth J, May G, Opelz G. Pretransplant IgA-anti-hinge and IgA-anti-Fab autoantibody activity is associated with good kidney graft survival. Transplant Proc. 1995 Oct;27(5):2663-5. — View Citation

Süsal C, Wiesel M, Schönemann C, Groth J, Carl S, Staehler G, May G, Opelz G. Presensitization and HLA match influence the predictive power of pretransplant serum IgA and IgA-anti-Fab autoantibodies in kidney graft recipients. Transplant Proc. 1997 Feb-Mar;29(1-2):1444-6. — View Citation

Süsal C, Wiesel M, Staehler G, Groth J, May G, Opelz G. Excellent kidney graft survival in patients with high pretransplant serum IgA concentrations and IgA-anti-Fab autoantibody activity. Transplant Proc. 1995 Feb;27(1):1072-4. — View Citation

Terness P, Navolan D, Kohl I, Siedler F, Moroder L, Dufter C, Welschof M, Schneider F, Drugarin D, Opelz G. Role of idiotype-independent anti-IgG autoantibodies in human kidney transplantation: natural anti-F(ab')2 antibodies recognize an IgG1 hinge region epitope. Transplant Proc. 1997 Feb-Mar;29(1-2):1412-4. — View Citation

Terness P, Navolan D, Moroder L, Siedler F, Weyher E, Kohl I, Dufter C, Welschof M, Drugarin D, Schneider F, Opelz G. A natural IgA-anti-F(ab')2gamma autoantibody occurring in healthy individuals and kidney graft recipients recognizes an IgG1 hinge region epitope. J Immunol. 1996 Nov 1;157(9):4251-7. — View Citation

Terness PI, Navolan D, Dufter C, Welschof M, Opelz G. Immunosuppressive anti-immunoglobulin autoantibodies: specificity, gene structure and function in health and disease. Cell Mol Biol (Noisy-le-grand). 2002 May;48(3):271-8. Review. — View Citation

Tyan DB, Li VA, Czer L, Trento A, Jordan SC. Intravenous immunoglobulin suppression of HLA alloantibody in highly sensitized transplant candidates and transplantation with a histoincompatible organ. Transplantation. 1994 Feb 27;57(4):553-62. — 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, Schweighoffer T, Schimpf K, Opelz G. Helper and suppressor T-cell function in HIV-infected hemophilia patients. Blood. 1989 Jul;74(1):298-302. — 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, Carl S, Staehler G, Opelz G. Superior 3-year kidney graft function in patients with impaired pretransplant Th2 responses. Transpl Int. 1998;11 Suppl 1:S350-6. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	patient survival		1 year / 3 years / 5 years posttransplant
Primary	graft survival		1 year / 3 years / 5 years posttransplant
Primary	acute rejection		1 year
Primary	chronic allograft nephropathy		3 years / 5 years posttransplant
Secondary	graft function		1 year / 3 years / 5 years
Secondary	infectious complications		1 year
Secondary	immunoglobulin levels		1 year
Secondary	regulatory autoantibody levels		1 year / 3 years / 5 years
Secondary	Th1 and Th2 responses		1 year / 3 years
Secondary	B-cell/monocyte responses		1 year / 3 years
Secondary	Expression of adhesion molecules, costimulatory molecules and cytokine receptors		1 year / 3 years
Secondary	proteinuria (quantitative assessment)		1 year / 3 years