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:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||Steroid-free and Long-term Calcineurin-free Trial in Islet Cell Transplantation|
- Measurement of Glycemic Control by HbA1c and Prevention of Severe Hypoglycemia [ Time Frame: 1 year ]Number of subjects at 1 year with HbA1c < 6.5% and absence of severe hypoglycemia
- Islet Allograft Function [ Time Frame: 1 year ]Number of subjects with basal C-peptide greater than 0.5 ng/ml
- Improvement in Metabolic Control as Evidenced by Hemoglobin A1c < 6.5% [ Time Frame: 1 year ]Number of subjects with a hemoglobin A1c < 6.5% at 1year after islet transplantation
- Elimination of Severe Hypoglycemia [ Time Frame: 1 year ]The number of subjects with severe hypoglycemia after transplantation
- Restoration of Hypoglycemia Awareness 1 Year After Transplantation [ Time Frame: 1 year ]The number of subjects with restoration of hypoglycemia awareness 1 year after islet transplantation
|Study Start Date:||July 2005|
|Study Completion Date:||January 2014|
|Primary Completion Date:||January 2014 (Final data collection date for primary outcome measure)|
Experimental: islet transplantation
Islet Alone Transplantation under Alentuzumab (Campath1H) induction.
Drug: Islet transplantation
Other Name: islet
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|