Steroid-free and Long-term Calcineurin-free Trial in Islet Cell Transplantation
Condition: Type 1 Diabetes Mellitus
MeSH terms: Diabetes Mellitus, Type 1
Study type: Interventional
Phase: Phase 2

Summary: 
      The purposes of this study are:

        1. To reverse hyperglycemia and insulin dependency in patients with type 1 diabetes
           mellitus through islet transplantation utilizing steroid free, calcineurin-inhibitor
           free immunosuppression.

        2. 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.

        3. To determine whether the natural history of the microvascular, macrovascular, and
           neuropathic complications are altered following the successful transplantation of
           islets.
    

Detailed description: 
      STUDY DESIGN:

      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:

        1. Zenapax, Rapamycin & MMF

        2. Campath, Rapamycin & MMF, and

        3. 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.
    

Intervention name(s): Islet transplantation
Intervention type(s): Drug
Intervention description(s): Islet transplantation
Other intervention name(s): islet
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Islet Transplantation