Renal Allograft Function and Histology Following Switching From A Tacrolimus to Sirolimus (SRL)-Based Immunosuppression-
Recruitment status was Recruiting
The investigators hypothesize that Tacrolimus (Tac) withdrawal from a Tac, MMF and steroid based triple therapy regimen leads to long term improved/stabilized graft function (glomerular filtration rate, GFR) primarily as a consequence of halting CNI-induced fibrogenetic processes that mediate loss of functioning renal tissue. The investigators further hypothesize that the underlying fibrotic mechanism is mediated by pathophysiologic processes that promote epithelial to mesenchymal transition (EMT) (mediated by TGF- ƒÒ) and that early therapeutic intervention may reverse this process (mediated by BMP-7)4.
To address these hypotheses the investigators propose the following clinical and mechanistic aims:
The investigators will test the hypothesis that switching from Tac to SRL in a Tac based triple therapy regimen with MMF and steroids in living and or deceased donor renal transplant recipients leads to improvement in allograft structure and function at 2 years post-transplantation.
The investigators will test this hypothesis in an open label controlled trial where stable renal allograft recipients on Tac, MMF, prednisone maintenance immunosuppression will undergo renal biopsy at 3-4 months post-transplantation and will be randomized to either a) Remain on Tac, MMF and prednisone (CNI-maintenance) or b) switch the Tac to SRL and continue MMF and prednisone. The investigators will then compare biopsy derived measures of allograft fibrosis (CADI, Sirius Red, Banff Chronicity Index) and GFR in the two groups
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Renal Allograft Function and Histology Following Switching From A Tacrolimus to Sirolimus (SRL)-Based Immunosuppression- Clinical and Mechanistic Impact|
- biopsy-derived measures of fibrosis [ Time Frame: 12 months ] [ Designated as safety issue: No ]The primary analyses will compare biopsy-derived measures of fibrosis in the Tac-maintenance and SRL groups using the t-test.
- change in iGFR [ Time Frame: 12 months ] [ Designated as safety issue: No ]We will also compare the change in iGFR (as well as estimated GFR) from time of conversion to 12 and 24 months of follow up by paired t-test between groups.
|Study Start Date:||July 2010|
|Estimated Study Completion Date:||December 2014|
|Estimated Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
Active Comparator: Sirolimus
patients will be switched from Tacrolimus to Sirolimus
Tacrolimus to SirolimusDrug: Tacrolimus
dosage per trough level
No Intervention: Tacrolimus
Patient will stay on Tacrolimus
Please refer to this study by its ClinicalTrials.gov identifier: NCT01166724
|Contact: Titte Srinvas, MD||216 445 0034|
|Contact: Emilio Poggio, MD||216 444 5383|
|United States, Ohio|
|Cleveland, Ohio, United States, 44195|
|Contact: Jennifer Czerr 216-444-3256|
|Contact: Leslie Iosue, RN 216 444 2991|
|Principal Investigator: Titte Srinivas, MD|
|Principal Investigator:||T Srinivas, MD||The Cleveland Clinic|