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Renal Failure, ChronicNCT00150891

Th1, Th2 and Monokine Responses as Risk Factors of Renal Transplant Rejection

An observational study of Renal Failure, Chronic, run by University of Giessen at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 14 years and older
Conditions the study is for
Renal Failure, Chronic
What is being tested?
Kidney transplantation, cyclosporine A and tacrolimus
Type of treatment
Surgery or procedure
How many people
84 participants
Where
1 siteGermany
Study dates
Jan 1998to Jan 2006
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 14 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Renal transplant recipients in the Giessen renal transplant unit

Who cannot join

  • Contraindications against blood-taking (anemia with hemoglobin<9.5 g/l, hypotension etc.)
  • No informed consent by the patient

Trial locations and contacts

1 site in 1 country.

Germany1 site
  • Department of Internal Medicine, University of Giessen

    Giessen, D-35392

Other trials in Germany

About this study

Official title: Role of Th1, Th2 and Monokine Responses as Risk Factors of Acute and Chronic Renal Transplant Rejection - Impact of Different Immunosuppressive Protocols

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 cell/monocyte 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.

Read the 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 cell/monocyte 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: CsA/Aza, CsA/MMF and Tacr/Aza; 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; 24(6): 2537-2538

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; 57(1): 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; 62(11): 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; 29(1-2): 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

Being tested
Kidney transplantation, cyclosporine A, tacrolimus, azathioprine, mycophenolate mofetil
Keywords
Th1, Th2, B cell, monokines, kidney transplantation, acute rejection, chronic rejection
Medical subject headings
Kidney Failure, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Sep 2005 (estimated)
  2. Study startJan 1998
  3. Study completionJan 2006

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Defined population
Time perspective
Prospective
Enrolment
84 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00150891
Sponsor's protocol ID
NTx-prosp-001
Status last verified
May 2007
First submitted
6 Sep 2005
Last updated
10 May 2007
Results posted
No
Data monitoring committee
No

Publications

  • 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. doi: 10.1097/01.TP.0000058808.37349.23.

    PubMed 12829918
  • 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. doi: 10.1016/s0198-8859(00)00152-x.

    PubMed 11053632
  • 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. doi: 10.1007/s001470050496.

    PubMed 9665014
  • 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 Feb-Mar;29(1-2):1079-80. doi: 10.1016/s0041-1345(96)00411-3. No abstract available.

    PubMed 9123208
  • 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. doi: 10.1097/00007890-199612150-00014.

    PubMed 8970616
  • 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. doi: 10.1097/00007890-199401000-00011.

    PubMed 7507271
  • 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. doi: 10.1016/s0041-1345(02)03278-5. No abstract available.

    PubMed 12270445
  • Weimer R, Staak A, Susal 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. doi: 10.1111/j.1432-2277.2004.00047.x.

    PubMed 15691277
  • 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. doi: 10.1016/j.transproceed.2005.02.088.

    PubMed 15919463
  • Weimer R, Susal C, Yildiz S, Staak A, Pelzl S, Renner F, Dietrich H, Daniel V, Kamali-Ernst S, Ernst W, Padberg W, Opelz G. Post-transplant sCD30 and neopterin as predictors of chronic allograft nephropathy: impact of different immunosuppressive regimens. Am J Transplant. 2006 Aug;6(8):1865-74. doi: 10.1111/j.1600-6143.2006.01407.x. Epub 2006 Jun 9.

    PubMed 16771810
  • Weimer R, Ettrich M, Renner F, Dietrich H, Susal C, Deisz S, Padberg W, Opelz G. ATG induction in renal transplant recipients: Long-term hazard of severe infection is associated with long-term functional T cell impairment but not the ATG-induced CD4 cell decline. Hum Immunol. 2014 Jun;75(6):561-9. doi: 10.1016/j.humimm.2014.02.015. Epub 2014 Feb 12.

    PubMed 24530759
  • Weimer R, Deisz S, Dietrich H, Renner F, Bodeker RH, Daniel V, Kamali-Ernst S, Ernst W, Padberg W, Opelz G. Impact of maintenance immunosuppressive regimens--balance between graft protective suppression of immune functions and a near physiological immune response. Transpl Int. 2011 Jun;24(6):596-609. doi: 10.1111/j.1432-2277.2011.01241.x. Epub 2011 Mar 14.

    PubMed 21401729

Questions about this trial

What is this clinical trial studying?

An observational study of Renal Failure, Chronic, run by University of Giessen at 1 site in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 May 2007. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00150891, which also lists 12 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 May 2007.

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