Immunoregulatory Effects of Immunoglobulin Induction Therapy in Renal Transplant Recipients - Full Text View

Purpose

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.

Condition	Intervention	Phase
Renal Failure, Chronic Renal Transplantation	Drug: intravenous immunoglobulins (IVIG) Procedure: kidney transplantation	Phase 0

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

Resource links provided by NLM:

MedlinePlus related topics: Kidney Transplantation

Drug Information available for: Rho(D) Immune Globulin

U.S. FDA Resources

Further study details as provided by University of Giessen:

Primary Outcome Measures:

patient survival [ Time Frame: 1 year / 3 years / 5 years posttransplant ]
graft survival [ Time Frame: 1 year / 3 years / 5 years posttransplant ]
acute rejection [ Time Frame: 1 year ]
chronic allograft nephropathy [ Time Frame: 3 years / 5 years posttransplant ]

Secondary Outcome Measures:

graft function [ Time Frame: 1 year / 3 years / 5 years ]
infectious complications [ Time Frame: 1 year ]
immunoglobulin levels [ Time Frame: 1 year ]
regulatory autoantibody levels [ Time Frame: 1 year / 3 years / 5 years ]
Th1 and Th2 responses [ Time Frame: 1 year / 3 years ]
B-cell/monocyte responses [ Time Frame: 1 year / 3 years ]
Expression of adhesion molecules, costimulatory molecules and cytokine receptors [ Time Frame: 1 year / 3 years ]
proteinuria (quantitative assessment) [ Time Frame: 1 year / 3 years ]

Enrollment:	50
Study Start Date:	October 2001
Study Completion Date:	May 2006

Detailed 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.

Eligibility

Ages Eligible for Study:	14 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00176059

Locations

Germany
Department of Internal Medicine, University of Giessen
Giessen, Germany

Sponsors and Collaborators

University of Giessen

University of Heidelberg

Astellas Pharma Inc

Hoffmann-La Roche

Aventis Pharmaceuticals

Investigators

Principal Investigator:

Rolf Weimer, Prof. Dr.

Department of Internal Medicine, University of Giessen, Giessen, Germany

More Information

Publications:

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;38(10):3483-5.

Weimer R, Susal 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.

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.

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.

Susal C, Dohler 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.

Susal C, Dorr 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.

Susal 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. No abstract available.

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

Susal C, Wiesel M, Schonemann 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. No abstract available.

Susal C, Kropelin 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. No abstract available.

Susal C, Kropelin 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. No abstract available.

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.

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. No abstract available.

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.

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.

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.

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.

ClinicalTrials.gov Identifier:	NCT00176059 History of Changes
Other Study ID Numbers:	NTx-Ig-003
Study First Received:	September 9, 2005
Last Updated:	May 8, 2007
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by University of Giessen:

immunoglobulins, intravenous
kidney transplantation
acute rejection
chronic rejection
regulatory autoantibodies

Th1
Th2
B Cell
Monokines
Cytokine promoter gene polymorphisms

Additional relevant MeSH terms:

Kidney Failure, Chronic
Renal Insufficiency
Renal Insufficiency, Chronic
Kidney Diseases
Urologic Diseases
Autoantibodies
Immunoglobulins

Antibodies
Immunoglobulins, Intravenous
Rho(D) Immune Globulin
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 23, 2013