Steroid-free and Long-term Calcineurin-free Trial in Islet Cell Transplantation
The purposes of this study are:
- To reverse hyperglycemia and insulin dependency in patients with type 1 diabetes mellitus through islet transplantation utilizing steroid free, calcineurin-inhibitor free immunosuppression.
- To assess the long-term function of successful islet transplants in patients with type 1 diabetes mellitus utilizing islets that have undergone a period of culture.
- To determine whether the natural history of the microvascular, macrovascular, and neuropathic complications are altered following the successful transplantation of islets.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Steroid-free and Long-term Calcineurin-free Trial in Islet Cell Transplantation|
- Steroid-free/calcineurin-free immunosuppression (Campath/sirolimus/mycophenolate mofetil [MMF]) will be as effective or better with less side effects than the use of the sirolimus/tacrolimus/daclizumab regimen. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- Secondary endpoints will include: partial graft function, as evidenced by basal C-peptide greater than 0.5 ng/ml; reduction in insulin requirements in those patients who do not achieve insulin independence [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- improvement in metabolic control as evidenced by improvement in: hemoglobin A1c [HbA1c] (should be < 6.5%) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- mean glucose meter readings, elimination or reduction in the incidence of hypoglycemic coma or unawareness [ Time Frame: 3 years ] [ Designated as safety issue: No ]
|Study Start Date:||July 2005|
|Estimated Study Completion Date:||December 2016|
|Estimated Primary Completion Date:||December 2016 (Final data collection date for primary outcome measure)|
|Experimental: islet transplantation||
Drug: Islet transplantation
The initial proposal submitted to the JDRFI was to compare 3 different groups of patients receiving islet cell transplants utilizing steroid-free, calcineurin-free protocols. The 3 groups were as follows:
- Zenapax, Rapamycin & MMF
- Campath, Rapamycin & MMF, and
- Thymoglobulin, Rapamycin & MMF.
The grant was awarded in December 2003, however the recommendations were to focus on a single group (group 3 or 4) in order to determine the relative efficacy and toxicity of a new immunosuppressive drug combination. We elected to perform the group utilizing Campath, since we have a similar protocol utilizing the same immunosuppressive regimen with the addition of CD34+ enriched donor bone marrow cells (2000/0024). The results of this trial utilizing a steroid-free/calcineurin-free protocol will be compared with the standard "Edmonton Protocol" (2000/0196), which we are currently conducting (14 patients have been transplanted). In addition, the results will be compared with those in 2000/0024.
Protocol 2000/0024 (utilizing the same immunosuppressive regimen; Campath, Rapamycin, Tacrolimus-switched to MMF at 3 months) is being followed by a DSMB established at the NIH.
We propose to evaluate 12 patients with steroid free, long term calcineurin inhibitor free immunosuppression regimens which can be directly compared to our historical group of patients who underwent the Miami version of the Edmonton protocol (Islet Cell Transplantation Alone in Patients with Type 1 Diabetes Mellitus: Steroid-Free Immunosuppression - Protocol # 2000/196) and with the concurrent tolerogenic protocol (Islet Cell Transplantation Alone and CD34+ Enriched Donor Bone Marrow Cell Infusion in Patients with Type 1 Diabetes Mellitus; Steroid Free Regimen - Protocol # 2000/0024) which uses the same immunosuppressive regimen combined with CD34+ stem cell enriched donor bone marrow infusions.
The regimen will consist of Campath 1-H induction, maintenance immunosuppression with sirolimus and tacrolimus for 3 months with subsequent introduction of mycophenolate mofetil (MMF) and removal of tacrolimus completely and TNF-alpha inhibition (etanercept) in the peri-transplant period.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00315627
|United States, Florida|
|Diabetes Research Institute|
|Miami, Florida, United States, 33136|
|Principal Investigator:||Rodolfo Alejandro, M.D.||Diabetes Research Institute - University of Miami|