Efficacy and Safety Study of Autologous Hematopoietic Stem Cell Transplantation to Treat New Onset Type 1 Diabetes
Condition: Type 1 Diabetes
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Study type: Interventional
Phase: Phase 2

Summary: 
      Type 1 diabetes is an autoimmune disease and results from T cell autoimmunity mediated
      destruction of the majority of insulin-producing pancreatic β-cells. Hence,the development of
      new therapies to control T cell autoimmunity, and to preserve the remaining β-cell function
      will be of great significance in managing patients with type 1 diabetes

      Autologous nonmyeloablative hematopoietic stem cell transplantation (AHST) has been tested
      for the treatment of patients with new onset of type 1 diabetes. This therapeutic strategy
      can result in exogenous insulin independence by destroying pathogenic memory T cells and
      preserving the remaining β-cell function.

      However, little is known about the efficacy of AHST in the dynamics of immunocompetent cell
      reconstitution and how the reconstituted immune system regulates β-cell specific antibody
      response. Furthermore, many Chinese patients at diagnosis of type 1 diabetes have progressed
      to develop diabetic ketoacidosis (DKA). Whether treatment with AHST could still achieve
      adequate glycemic control and preserve the β-cell function and what the factors are
      associated with the therapeutic efficacy have not been explored.

      This is a phase Ⅱ clinical trial in patients who have been diagnosed with type 1 diabetes
      within the previous 12 months.This study is to determine:

        -  The effects of autologous hematopoietic stem cell transplantation on the reconstitution
           of immune system

        -  β-cell preservation following stem cell transplantation

        -  The potential factors affecting efficacy of stem cell transplantation

        -  Whether this new therapy is safe.
    

Detailed description: 
      Patients diagnosed with type 1 diabetes within the previous 12 months will be recruited into
      this study.Hematopoietic stem cells were mobilized with cyclophosphamide (CY, 2.0g/m2) and
      granulocyte colony stimulating factor (10 μg/kg per day) and then collected from peripheral
      blood by leukapheresis and cryopreserved. The cells were infused after conditioning with CY
      (200 mg/kg) and rabbit antithymocyte globulin (4.5 mg/kg). All the included patients
      undergoing AHST complied with blood glucose self-monitoring and scheduled medical
      appointments.Their blood samples were obtained for measuring the frequency of lymphocytes and
      the levels of plasma hemoglobin A1c (HbA1c), serum C-peptide, islet antibodies, and cytokines
      longitudinally.

      Ages Eligible for Study: no more than 35 years

      Genders Eligible for Study: both

      Islet Autoantibodies Eligible for Study: positive for glutamic acid decarboxylase antibody
      (GADA), protein tyrosine phosphatase antibody (IA-2A), islet cell antibody (ICA) and/or
      insulin autoantibody (IAAs)
    

Intervention name(s): immunosuppression and stem cell transplantation
Intervention type(s): Procedure
Intervention description(s): Hematopoietic stem cells were mobilized with cyclophosphamide (CY, 2.0 g/m2) and granulocyte colonystimulating factor (10 μg/kg per day) and then collected from peripheral blood by leukapheresis and cryopreserved. The cells were infused after conditioning with CY (200 mg/kg) and rabbit antithymocyte globulin (4.5 mg/kg).
Other intervention name(s): nonmyeloablative stem cell transplantation
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Type 1 diabetes; stem cell; C-peptide; Immune function