Renal TransplantationPhase 4NCT00204321
Influence of Sirolimus and MMF on Vascular Function and Markers of Cellular Function in Renal Transplant Recipients
A Phase 4 study testing sirolimus (drug), mmf (drug) in people with Renal Transplantation, run by University Hospital Muenster at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Renal Transplantation
- What is being tested?
- sirolimus (drug), mmf (drug)
- How many people
- 80 participants
- Where
- 1 siteGermany
- Study dates
- Jun 2005to Jan 2010
- Phase
- Phase 4
- 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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- renal transplantation stable function
Who cannot join
- acute rejection
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Discontinuing of calcineurininhibitors will lead to improvement of vessel wall function 2. Sirolimus and Mycophenolat Mofetil affect vessel wall properties in a different way.
- 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.
- Calcineurininhibitorfree immunosuppression reduces the activity of endothelial cells.
- Survival of monocytes and release of procoagulatory activity will be changed by the immunosuppressive regimen.
- Rostand SG, Brunzell JD, Cannon RO, Victor RG. Cardiovascular complications in renal failure. J Am Soc Nephrol. 1991; 2: 1053-1062
- London GM, Druecke TB. Atherosclerosis and arteriosclerosis in chronic renal failure. Kidney Int 1997; 51(6):1678-1695.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Österud, A., Björklid E. Role of monocytes in atherogenesis. Physiological reviews, 2003, 83: 1069-1112.
- Ross R. Atherosclerosis--an inflammatory disease. N Engl J Med. 1999 Jan 14;340(2):115-26.
- 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.
- Conditions
- Renal Transplantation
- Being tested
- sirolimus (drug), mmf (drug)
- Keywords
- rejection, vesselwall function, endothelial cell function, monocytes
- Medical subject headings
- Rejection, Psychology
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sirolimus (drug), mmf (drug)Drug
What is being measured
The primary outcome is the main question the study is designed to answer.
distensibility
sympathetic nervous system activity
endothelial cell marker expression
Secondary outcomes (1)
monocyte survival
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2005 (estimated)
- Study startJun 2005
- Primary completionJan 2008
- Study completionJan 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Renal TransplantationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital Muenster
- Sponsor type
- University, hospital or other
- Collaborators
- Else Kröner Fresenius Foundation
- Investigators
- Martin Hausberg, MD, Principal investigator, UKM - Medical Department D
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00204321
- Sponsor's protocol ID
- Hausberg_Lang-Sir/MMF
- Other IDs
- EKF Hausberg Lang
- Status last verified
- Jan 2010
- First submitted
- 12 Sep 2005
- Last updated
- 13 Jan 2010
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00204321
- Acronym / sponsor ID
- Hausberg_Lang-Sir/MMF
- Conditions
- Renal Transplantation
- Keywords
- rejection, vesselwall function, endothelial cell function, monocytes
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- University Hospital MuensterUniversity, hospital or other
- Collaborators
- Else Kröner Fresenius Foundation
- Study start
- Jun 2005
- Primary completion
- Jan 2008 (actual)
- Study completion
- Jan 2010 (actual)
- First posted
- 20 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
- Discontinuing of calcineurininhibitors will lead to improvement of vessel wall function 2. Sirolimus and Mycophenolat Mofetil affect vessel wall properties in a different way.
- 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.
- Calcineurininhibitorfree immunosuppression reduces the activity of endothelial cells.
- Survival of monocytes and release of procoagulatory activity will be changed by the immunosuppressive regimen.
- Rostand SG, Brunzell JD, Cannon RO, Victor RG. Cardiovascular complications in renal failure. J Am Soc Nephrol. 1991; 2: 1053-1062
- London GM, Druecke TB. Atherosclerosis and arteriosclerosis in chronic renal failure. Kidney Int 1997; 51(6):1678-1695.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Österud, A., Björklid E. Role of monocytes in atherogenesis. Physiological reviews, 2003, 83: 1069-1112.
- Ross R. Atherosclerosis--an inflammatory disease. N Engl J Med. 1999 Jan 14;340(2):115-26.
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- renal transplantation stable function
Key exclusion criteria (1 listed)
- acute rejection
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sirolimus (drug), mmf (drug) | Drug | – |
Primary outcome
distensibility
sympathetic nervous system activity
endothelial cell marker expression
1 secondary outcome
monocyte survival
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2010.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Martin Hausberg, MD principal investigator
UKM - Medical Department D
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing sirolimus (drug), mmf (drug) in people with Renal Transplantation, run by University Hospital Muenster 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 1 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 13 Jan 2010. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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.
What does the primary outcome measure?
distensibility. The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Jan 2010.