Ignite Creation Date:
2024-05-05 @ 12:00 PM
Last Modification Date:
2024-10-26 @ 9:18 AM
Study NCT ID:
NCT00204321
Status:
COMPLETED
Last Update Posted:
2010-01-13
First Post:
2005-09-12
Brief Title:
Influence of Sirolimus and MMF on Vascular Function and Markers of Cellular Function in Renal Transplant Recipients
Sponsor:
University Hospital Muenster
Organization:
University Hospital Muenster
Study Overview
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
Status:
COMPLETED
Status Verified Date:
2010-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 andor 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
Vascular changes induced by hypertension andor 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
Detailed Description:
Cardiovascular complications and chronic rejection are chief causes of transplant loss12 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 45 Additionally the activation of sympathetic nervous system leads to dysfunction of vessel wall67 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 eg 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 5161678-1695
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 2079-84
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 65700-704
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 3271912-1918
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 1061974-9
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 20501-8
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 143402115-26
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 Jun16062145-55
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 eg 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 5161678-1695
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 2079-84
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 65700-704
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 3271912-1918
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 1061974-9
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 20501-8
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 143402115-26
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 Jun16062145-55
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| EKF Hausberg Lang | None | None | None |