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

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ClinicalTrials.gov Identifier: NCT00204321
Recruitment Status : Completed
First Posted : September 20, 2005
Last Update Posted : January 13, 2010
Else Kröner Fresenius Foundation
Information provided by:
University Hospital Muenster

Brief Summary:

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 or disease Intervention/treatment Phase
Renal Transplantation Drug: sirolimus (drug), mmf (drug) Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Study Start Date : June 2005
Actual Primary Completion Date : January 2008
Actual Study Completion Date : January 2010

Resource links provided by the National Library of Medicine

Drug Information available for: Sirolimus

Primary Outcome Measures :
  1. distensibility
  2. sympathetic nervous system activity
  3. endothelial cell marker expression

Secondary Outcome Measures :
  1. monocyte survival

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

renal transplantation stable function

Exclusion Criteria:

acute rejection

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00204321

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Münster, NRW, Germany, 48149
Sponsors and Collaborators
University Hospital Muenster
Else Kröner Fresenius Foundation
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Principal Investigator: Martin Hausberg, MD UKM - Medical Department D
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Responsible Party: Prof. Dr. Hausberg, UKM
ClinicalTrials.gov Identifier: NCT00204321    
Other Study ID Numbers: Hausberg_Lang-Sir/MMF
EKF Hausberg Lang
First Posted: September 20, 2005    Key Record Dates
Last Update Posted: January 13, 2010
Last Verified: January 2010
Keywords provided by University Hospital Muenster:
vesselwall function
endothelial cell function
Additional relevant MeSH terms:
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Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs