Influence of Sirolimus and MMF on Vascular Function and Markers of Cellular Function in Renal Transplant Recipients

This study has been completed.
Sponsor:
Collaborator:
Else Kröner Fresenius Foundation
Information provided by:
University Hospital Muenster
ClinicalTrials.gov Identifier:
NCT00204321
First received: September 12, 2005
Last updated: January 12, 2010
Last verified: January 2010
  Purpose

Chronic transplant nephropathy and cardiovascular death are the main reasons for loss of transplanted organs after kidney transplantation.

Vascular changes, induced by hypertension and/or immunological processes, determine long time transplant survival.

It will be tested whether the withdrawal of calcineurininhibitors will improve the vessel wall function in renal transplant patients. It is supposed that this immunosuppressive regimen reduces the activation of endothelial cells with important impact on arteriosclerosis and therefore on patient and transplant survival.


Condition Intervention Phase
Renal Transplantation
Drug: sirolimus (drug), mmf (drug)
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Influence of Sirolimus and MMF on Vascular Function and Markers of Cellular Function in Renal Transplant Recipients - Positive Effects of Calcineurin-free Immunosuppression

Resource links provided by NLM:


Further study details as provided by University Hospital Muenster:

Primary Outcome Measures:
  • distensibility
  • sympathetic nervous system activity
  • endothelial cell marker expression

Secondary Outcome Measures:
  • monocyte survival

Estimated Enrollment: 80
Study Start Date: June 2005
Study Completion Date: January 2010
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Detailed Description:

Cardiovascular complications and chronic rejection are chief causes of transplant loss[1,2]. After renal transplantation patients are still characterized by their pre-existing arteriosclerotic changes [3]. Endothelial dysfunction and disturbed distensibility of great arteries are independent predictors of cardiovascular morbidity [4,5]. Additionally the activation of sympathetic nervous system leads to dysfunction of vessel wall[6,7]. There are important therapeutic options in improvement of endothelial function [8].

In addition monocytes of the recipient will contribute to vessel wall changes. [9-11]. Aim of therapy - especially of immunosuppressive therapy- have to prevent these fatal vessel wall changes.

Therefore in this study the following topics will be addressed.

1. Discontinuing of calcineurininhibitors will lead to improvement of vessel wall function 2. Sirolimus and Mycophenolat Mofetil affect vessel wall properties in a different way.

3. There are risk factors, e.g. activity of sympathetic nervous system, which may determine the efficacy of discontinuing the calcineurininhibitor concerning the vessel wall function.

4. Calcineurininhibitorfree immunosuppression reduces the activity of endothelial cells.

5. Survival of monocytes and release of procoagulatory activity will be changed by the immunosuppressive regimen.

  1. Rostand SG, Brunzell JD, Cannon RO, Victor RG. Cardiovascular complications in renal failure. J Am Soc Nephrol. 1991; 2: 1053-1062
  2. London GM, Druecke TB. Atherosclerosis and arteriosclerosis in chronic renal failure. Kidney Int 1997; 51(6):1678-1695.
  3. Hausberg, M., K. Kisters, M. Kosch, K. H. Rahn, and M. Barenbrock. Flow-mediated vasodilation and distensibility of the brachial artery in renal allograft recipients. Kidney Int. 55: 1104-1110, 1999.
  4. Barenbrock M, Kosch M, Jöster E, Kisters K, Rahn KH, Hausberg M: Reduced arterial distensibility is a predictor of cardiovascular disease in patients after renal transplantation. Journal of Hypertension 2002, 20:79-84.
  5. London GM, Pannier B, Agharazii M, Guerin AP, Verbeke FHM, Marchais SY. Forearm reactive hyperemia and mortality in end-stage-disease. Kidney Int 2004, 65:700-704.
  6. Converse RL, Jacobsen TN, Toto RD, Jost CMT, Cosentino F, Fouad-Tarazi F, Victor RG. Sympathetic overactivity in patients with chronic renal failure. N Engl J Med 1992; 327:1912-1918.
  7. Hausberg M, Kosch M, Harmelink P, Barenbrock M, Hohage H, Kisters K, Dietl KH, Rahn KH. Sympathetic nerve activity in end-stage renal disease. Circulation. 2002, 106:1974-9.
  8. Kosch M, Barenbrock M, Kisters K, Rahn KH, Hausberg M. Relationship between muscle sympathetic nerve activity and large artery mechanical vessel wall properties in renal transplant patients. J Hypertens. 2002, 20:501-8.
  9. Österud, A., Björklid E. Role of monocytes in atherogenesis. Physiological reviews, 2003, 83: 1069-1112.
  10. Ross R. Atherosclerosis--an inflammatory disease. N Engl J Med. 1999 Jan 14;340(2):115-26.
  11. Lessner SM, Prado HL, Waller EK, Galis ZS. Atherosclerotic lesions grow through recruitment and proliferation of circulating monocytes in a murine model. Am J Pathol. 2002 Jun;160(6):2145-55.
  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

renal transplantation stable function

Exclusion Criteria:

acute rejection

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00204321

Locations
Germany
UKM
Münster, NRW, Germany, 48149
Sponsors and Collaborators
University Hospital Muenster
Else Kröner Fresenius Foundation
Investigators
Principal Investigator: Martin Hausberg, MD UKM - Medical Department D
  More Information

No publications provided

Responsible Party: Prof. Dr. Hausberg, UKM
ClinicalTrials.gov Identifier: NCT00204321     History of Changes
Other Study ID Numbers: Hausberg_Lang-Sir/MMF, EKF Hausberg Lang
Study First Received: September 12, 2005
Last Updated: January 12, 2010
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by University Hospital Muenster:
rejection
vesselwall function
endothelial cell function
monocytes

Additional relevant MeSH terms:
Sirolimus
Everolimus
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 02, 2014